Pharmaceutics

2023

Jump to: 2022, 2021, 2020

21 pages, 4738 KiB

Open AccessEditor’s ChoiceArticle

Characterization and In Vivo Antiangiogenic Activity Evaluation of Morin-Based Cyclodextrin Inclusion Complexes

by Federica De Gaetano, Fatima Margani, Vincenzina Barbera, Valeria D’Angelo, Maria Paola Germanò, Venerando Pistarà and Cinzia Anna Ventura

Pharmaceutics 2023, 15(9), 2209; https://doi.org/10.3390/pharmaceutics15092209 - 26 Aug 2023

Cited by 7 | Viewed by 1261

Abstract

Morin (MRN) is a natural compound with antiangiogenic, antioxidant, anti-inflammatory, and anticancer activity. However, it shows a very low water solubility (28 μg/mL) that reduces its oral absorption, making bioavailability low and unpredictable. To improve MRN solubility and positively affect its biological activity, [...] Read more.

Morin (MRN) is a natural compound with antiangiogenic, antioxidant, anti-inflammatory, and anticancer activity. However, it shows a very low water solubility (28 μg/mL) that reduces its oral absorption, making bioavailability low and unpredictable. To improve MRN solubility and positively affect its biological activity, particularly its antiangiogenic activity, in this work, we prepared the inclusion complexes of MNR with sulfobutylether-β-cyclodextrin (SBE-β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion complexes obtained by the freeze-drying method were extensively characterized in solution (phase-solubility studies, UV–Vis titration, and NMR spectroscopy) and in the solid state (TGA, DSC, and WAXD analysis). The complexation significantly increased the water solubility by about 100 times for MRN/HP-β-CD and 115 times for MRN/SBE-β-CD. Furthermore, quantitative dissolution of the complexes was observed within 60 min, whilst 1% of the free drug dissolved in the same experimental time. ¹H NMR and UV–Vis titration studies demonstrated both CDs well include the benzoyl moiety of the drug. Additionally, SBE-β-CD could interact with the cinnamoyl moiety of MRN too. The complexes are stable in solution, showing a high value of association constant, that is, 3380 M⁻¹ for MRN/HP-β-CD and 2870 M⁻¹ for MRN/SBE-β-CD. In vivo biological studies on chick embryo chorioallantoic membrane (CAM) and zebrafish embryo models demonstrated the high biocompatibility of the inclusion complexes and the effective increase in antiangiogenic activity of complexed MRN with respect to the free drug. Full article

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2022

Jump to: 2023, 2021, 2020

32 pages, 5221 KiB

Open AccessArticle

A Micro-Configured Multiparticulate Reconstitutable Suspension Powder of Fixed Dose Rifampicin and Pyrazinamide: Optimal Fabrication and In Vitro Quality Evaluation

by Penelope N. Rampedi, Modupe O. Ogunrombi, James Wesley-Smith and Oluwatoyin A. Adeleke

Pharmaceutics 2023, 15(1), 64; https://doi.org/10.3390/pharmaceutics15010064 - 25 Dec 2022

Cited by 4 | Viewed by 2666

Abstract

The scarcity of age-appropriate pharmaceutical formulations is one of the major challenges impeding successful management of tuberculosis (TB) prevalence in minors. To this end, we designed and assessed the quality of a multiparticulate reconstitutable suspension powder containing fixed dose rifampicin and pyrazinamide (150 [...] Read more.

The scarcity of age-appropriate pharmaceutical formulations is one of the major challenges impeding successful management of tuberculosis (TB) prevalence in minors. To this end, we designed and assessed the quality of a multiparticulate reconstitutable suspension powder containing fixed dose rifampicin and pyrazinamide (150 mg/300 mg per 5 mL) which was prepared employing solid–liquid direct dispersion coupled with timed dehydration, and mechanical pulverization. The optimized formulation had a high production yield (96.000 ± 3.270%), displayed noteworthy powder flow quality (9.670 ± 1.150°), upon reconstitution the suspension flow property was non-Newtonian and was easily redispersible with gentle manual agitation (1.720 ± 0.011 strokes/second). Effective drug loading was attained for both pyrazinamide (97.230 ± 2.570%w/w) and rifampicin (97.610 ± 0.020%w/w) and drug release followed a zero-order kinetic model (R² = 0.990) for both drugs. Microscopic examinations confirmed drug encapsulation efficiency and showed that the particulates were micro-dimensional in nature (n < 700.000 µm). The formulation was physicochemically stable with no chemically irreversible drug-excipient interactions based on the results of characterization experiments performed. Findings from organoleptic evaluations generated an overall rating of 4.000 ± 0.000 for its attractive appearance and colour 5.000 ± 0.000 confirming its excellent taste and extremely pleasant smell. Preliminary cytotoxicity studies showed a cell viability above 70.000% which indicates that the FDC formulation was biocompatible. The optimized formulation was environmentally stable either as a dry powder or reconstituted suspension. Accordingly, a stable and palatable FDC antimycobacterial reconstitutable oral suspension powder, intended for flexible dosing in children and adolescents, was optimally fabricated. Full article

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21 pages, 2273 KiB

Open AccessArticle

Glycolytic Inhibitors Potentiated the Activity of Paclitaxel and Their Nanoencapsulation Increased Their Delivery in a Lung Cancer Model

by Andrea Cunha, Ana Catarina Rocha, Flávia Barbosa, Ana Baião, Patrícia Silva, Bruno Sarmento and Odília Queirós

Pharmaceutics 2022, 14(10), 2021; https://doi.org/10.3390/pharmaceutics14102021 - 23 Sep 2022

Cited by 10 | Viewed by 2792

Abstract

Antiglycolytic agents inhibit cell metabolism and modify the tumor’s microenvironment, affecting chemotherapy resistance mechanisms. In this work, we studied the effect of the glycolytic inhibitors 3-bromopyruvate (3BP), dichloroacetate (DCA) and 2-deoxyglucose (2DG) on cancer cell properties and on the multidrug resistance phenotype, using [...] Read more.

Antiglycolytic agents inhibit cell metabolism and modify the tumor’s microenvironment, affecting chemotherapy resistance mechanisms. In this work, we studied the effect of the glycolytic inhibitors 3-bromopyruvate (3BP), dichloroacetate (DCA) and 2-deoxyglucose (2DG) on cancer cell properties and on the multidrug resistance phenotype, using lung cancer cells as a model. All compounds led to the loss of cell viability, with different effects on the cell metabolism, migration and proliferation, depending on the drug and cell line assayed. DCA was the most promising compound, presenting the highest inhibitory effect on cell metabolism and proliferation. DCA treatment led to decreased glucose consumption and ATP and lactate production in both A549 and NCI-H460 cell lines. Furthermore, the DCA pretreatment sensitized the cancer cells to Paclitaxel (PTX), a conventional chemotherapeutic drug, with a 2.7-fold and a 10-fold decrease in PTX IC₅₀ values in A549 and NCI-H460 cell lines, respectively. To increase the intracellular concentration of DCA, thereby potentiating its effect, DCA-loaded poly(lactic-co-glycolic acid) nanoparticles were produced. At higher DCA concentrations, encapsulation was found to increase its toxicity. These results may help find a new treatment strategy through combined therapy, which could open doors to new treatment approaches. Full article

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32 pages, 7463 KiB

Open AccessReview

Prevention and Eradication of Biofilm by Dendrimers: A Possibility Still Little Explored

by Silvana Alfei and Debora Caviglia

Pharmaceutics 2022, 14(10), 2016; https://doi.org/10.3390/pharmaceutics14102016 - 22 Sep 2022

Cited by 9 | Viewed by 2589

Abstract

Multidrug resistance (MDR) among pathogens and the associated infections represent an escalating global public health problem that translates into raised mortality and healthcare costs. MDR bacteria, with both intrinsic abilities to resist antibiotics treatments and capabilities to transmit genetic material coding for further [...] Read more.

Multidrug resistance (MDR) among pathogens and the associated infections represent an escalating global public health problem that translates into raised mortality and healthcare costs. MDR bacteria, with both intrinsic abilities to resist antibiotics treatments and capabilities to transmit genetic material coding for further resistance to other bacteria, dramatically decrease the number of available effective antibiotics, especially in nosocomial environments. Moreover, the capability of several bacterial species to form biofilms (BFs) is an added alarming mechanism through which resistance develops. BF, made of bacterial communities organized and incorporated into an extracellular polymeric matrix, self-produced by bacteria, provides protection from the antibiotics’ action, resulting in the antibiotic being ineffective. By adhering to living or abiotic surfaces present both in the environment and in the healthcare setting, BF causes the onset of difficult-to-eradicate infections, since it is difficult to prevent its formation and even more difficult to promote its disintegration. Inspired by natural antimicrobial peptides (NAMPs) acting as membrane disruptors, with a low tendency to develop resistance and demonstrated antibiofilm potentialities, cationic polymers and dendrimers, with similar or even higher potency than NAMPs and with low toxicity, have been developed, some of which have shown in vitro antibiofilm activity. Here, aiming to incite further development of new antibacterial agents capable of inhibiting BF formation and dispersing mature BF, we review all dendrimers developed to this end in the last fifteen years. The extension of the knowledge about these still little-explored materials could be a successful approach to find effective weapons for treating chronic infections and biomaterial-associated infections (BAIs) sustained by BF-producing MDR bacteria. Full article

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11 pages, 1293 KiB

Open AccessArticle

Isosteviol Sodium (STVNA) Reduces Pro-Inflammatory Cytokine IL-6 and GM-CSF in an In Vitro Murine Stroke Model of the Blood–Brain Barrier (BBB)

by Moritz Reschke, Ellaine Salvador, Nicolas Schlegel, Malgorzata Burek, Srikanth Karnati, Christian Wunder and Carola Y. Förster

Pharmaceutics 2022, 14(9), 1753; https://doi.org/10.3390/pharmaceutics14091753 - 23 Aug 2022

Cited by 4 | Viewed by 2373

Abstract

Early treatment with glucocorticoids could help reduce both cytotoxic and vasogenic edema, leading to improved clinical outcome after stroke. In our previous study, isosteviol sodium (STVNA) demonstrated neuroprotective effects in an in vitro stroke model, which utilizes oxygen-glucose deprivation (OGD). Herein, we tested [...] Read more.

Early treatment with glucocorticoids could help reduce both cytotoxic and vasogenic edema, leading to improved clinical outcome after stroke. In our previous study, isosteviol sodium (STVNA) demonstrated neuroprotective effects in an in vitro stroke model, which utilizes oxygen-glucose deprivation (OGD). Herein, we tested the hypothesis that STVNA can activate glucocorticoid receptor (GR) transcriptional activity in brain microvascular endothelial cells (BMECs) as previously published for T cells. STVNA exhibited no effects on transcriptional activation of the glucocorticoid receptor, contrary to previous reports in Jurkat cells. However, similar to dexamethasone, STVNA inhibited inflammatory marker IL-6 as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion. Based on these results, STVNA proves to be beneficial as a possible prevention and treatment modality for brain ischemia-reperfusion injury-induced blood–brain barrier (BBB) dysfunction. Full article

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25 pages, 5303 KiB

Open AccessArticle

Influence of Technological Factors on the Quality of Chitosan Microcapsules with Boswellia serata L. Essential Oil

by Lauryna Pudziuvelyte, Aiste Siauruseviciute, Ramune Morkuniene, Robertas Lazauskas and Jurga Bernatoniene

Pharmaceutics 2022, 14(6), 1259; https://doi.org/10.3390/pharmaceutics14061259 - 13 Jun 2022

Cited by 4 | Viewed by 2314

Abstract

Essential oils contain many volatile compounds that are not stable and lose their pharmacological effect when exposed to the environment. The aim of this study is to protect Boswellia serrata L. essential oil from environmental factors by encapsulation and determine the influence of [...] Read more.

Essential oils contain many volatile compounds that are not stable and lose their pharmacological effect when exposed to the environment. The aim of this study is to protect Boswellia serrata L. essential oil from environmental factors by encapsulation and determine the influence of chitosan concentration and types (2%, 4%; medium and high molecular weights), essential oil concentration, different emulsifiers (Tween and Span), and technological factors (stirring time, launch height, drip rate) on the physical parameters, morphology, texture, and other parameters of the generated gels, emulsions, and microcapsules. For the first time, Boswellia serrata L. essential oil microcapsules with chitosan were prepared by coacervation. Hardness, consistency, stickiness, viscosity, and pH of chitosan gels were tested. Freshly obtained microcapsules were examined for moisture, hardness, resistance to compression, size, and morphology. Results show that different molecular weights and concentrations of chitosan affected gel hardness, consistency, stickiness, viscosity, mobility, and adhesion. An increase in chitosan concentration from 2% to 4% significantly changed the appearance of the microcapsules. It was found that spherical microcapsules were formed when using MMW and HMW 80/1000 chitosan. Chitosan molecular weight, concentration, essential oil concentration, and stirring time all had an impact on the hardness of the microcapsules and their resistance to compression. Full article

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16 pages, 2848 KiB

Open AccessArticle

Merging Experimental Design and Nanotechnology for the Development of Optimized Simvastatin Spanlastics: A Promising Combined Strategy for Augmenting the Suppression of Various Human Cancer Cells

by Shaimaa M. Badr-Eldin, Hibah M. Aldawsari, Nabil A. Alhakamy, Usama A. Fahmy, Osama A. A. Ahmed, Thikryat Neamatallah, Singkome Tima, Raghad H. Almaghrabi, Fayda M. Alkudsi, Asmaa A. Alamoudi, Amjad A. Alzahrani, Sabna Kotta and Omar D. Al-hejaili

Pharmaceutics 2022, 14(5), 1024; https://doi.org/10.3390/pharmaceutics14051024 - 9 May 2022

Cited by 6 | Viewed by 2677

Abstract

Simvastatin (SMV) is an antihyperlipidemic agent that has been investigated as a possible anti-cancer agent. An obstacle to malignant tumor therapy using drugs is the delivery of adequate levels to the cancer cells while minimizing side effects following their systemic administration. To circumvent [...] Read more.

Simvastatin (SMV) is an antihyperlipidemic agent that has been investigated as a possible anti-cancer agent. An obstacle to malignant tumor therapy using drugs is the delivery of adequate levels to the cancer cells while minimizing side effects following their systemic administration. To circumvent this challenge, the researchers directed towards the field of nanotechnology to benefit from the nano-size of the formulation in passively targeting the tumor cells. Thus, our study aimed at investigating the potential of a combined mixture–process variable design for optimization of SMV spanlastics (SMV-SPNs) with minimized particle size and maximized zeta potential to enhance the anticancer activity of the drug. The study investigated the effects of Span^® 20 and Tween^® 80 as mixture components and sonication time as a process variable on particle size, polydispersity index, and zeta potential as responses. SPNs were prepared using an ethanol injection method. Combining the predicted optimized variables’ levels is supposed to achieve the set goals with a desirability of 0.821. The optimized spanlastics exhibited a measured globule size of 128.50 nm, PDI of 0.329, and ZP of −29.11 mV. The percentage relative error between predicted responses and the observed ones were less than 5% for the three responses, indicating the optimization technique credibility. A significant improvement in the cytotoxicity of the optimized formulation against three different cancerous cell lines was observed in comparison with SMV. The inhibitory concentration (IC₅₀) values of MCF-7, HCT-116, and HEPG2 were found to be 0.89, 0.39, and 0.06 μM at 24 h incubation. The enhanced cytotoxicity could be assigned to the possible improved permeation and preferential build-up within the cancerous cells by virtue of the minimized size. These findings imply that SMV-SPNs could be an ideal strategy to combat cancer. Full article

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15 pages, 3322 KiB

Open AccessArticle

Optimization of Naringin and Naringenin Extraction from Citrus × paradisi L. Using Hydrolysis and Excipients as Adsorbent

by Jolita Stabrauskiene, Mindaugas Marksa, Liudas Ivanauskas and Jurga Bernatoniene

Pharmaceutics 2022, 14(5), 890; https://doi.org/10.3390/pharmaceutics14050890 - 19 Apr 2022

Cited by 25 | Viewed by 3977

Abstract

While flavanones exist in a variety of chemical forms, their favorable health effects are most prominent in their free form—aglycones. Their concentrations in grapefruit (Citrus × paradisi L.) extracts vary according to the extraction and hydrolysis methods used. The primary aim of [...] Read more.

While flavanones exist in a variety of chemical forms, their favorable health effects are most prominent in their free form—aglycones. Their concentrations in grapefruit (Citrus × paradisi L.) extracts vary according to the extraction and hydrolysis methods used. The primary aim of this work was to maximize the yields of naringin and naringenin from various parts of fresh grapefruit fruits (flavedo, albedo, and segmental) using different extraction and hydrolysis methods. In addition, we aimed to evaluate the excipient—magnesium aluminometasilicate—and determine its influence on the qualitative composition of grapefruit extracts. Extracts were obtained by heat reflux extraction (HRE), ultrasound-assisted extraction with an ultrasonic homogenizer (UAE*), and ultrasound-assisted extraction with a bath (UAE). Ultrasound-assisted extraction using a bath (UAE) was modulated using acidic, thermal, and alkaline hydrolysis. The highest yield of naringin 8A (17.45 ± 0.872 mg/g) was obtained from an albedo sample under optimal conditions using ultrasound-assisted extraction; a high yield of naringenin 23-SHR (35.80 ± 1.79 µg/g) was produced using the heat reflux method from the segmental part. Meanwhile, ultrasonic combined with thermal hydrolysis significantly increased flavanone extraction from the albedo and segmental parts: naringin from sample 9-A (from 17.45 ± 0.872 mg/g to 25.05 ± 1.25 mg/g) and naringenin from sample 15-S (from 0 to 4.21 ± 0.55 µg/g). Additionally, magnesium aluminometasilicate demonstrated significant increases of naringenin from all treated grapefruit parts. To our knowledge, this is the first report of magnesium aluminometasilicate used as an adsorbent in flavanone extractions. Full article

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2021

Jump to: 2023, 2022, 2020

15 pages, 2248 KiB

Open AccessArticle

Effects of Adipose-Derived Biogenic Nanoparticle-Associated microRNA-451a on Toll-like Receptor 4-Induced Cytokines

by Xinghua Wang, Anthony Pham, Lu Kang, Sierra A. Walker, Irina Davidovich, Dalila Iannotta, Sarvam P. TerKonda, Shane Shapiro, Yeshayahu Talmon, Si Pham and Joy Wolfram

Pharmaceutics 2022, 14(1), 16; https://doi.org/10.3390/pharmaceutics14010016 - 22 Dec 2021

Cited by 18 | Viewed by 3887

Abstract

Extracellular vesicles (EVs) are cell-released nanoparticles that transfer biomolecular content between cells. Among EV-associated biomolecules, microRNAs (miRNAs/miRs) represent one of the most important modulators of signaling pathways in recipient cells. Previous studies have shown that EVs from adipose-derived mesenchymal stromal cells (MSCs) and [...] Read more.

Extracellular vesicles (EVs) are cell-released nanoparticles that transfer biomolecular content between cells. Among EV-associated biomolecules, microRNAs (miRNAs/miRs) represent one of the most important modulators of signaling pathways in recipient cells. Previous studies have shown that EVs from adipose-derived mesenchymal stromal cells (MSCs) and adipose tissue modulate inflammatory pathways in macrophages. In this study, the effects of miRNAs that are abundant in adipose tissue EVs and other biogenic nanoparticles (BiNPs) were assessed in terms of altering Toll-like receptor 4 (TLR4)-induced cytokines. TLR-4 signaling in macrophages is often triggered by pathogen or damage-induced inflammation and is associated with several diseases. This study demonstrates that miR-451a, which is abundant in adipose tissue BiNPs, suppresses pro-inflammatory cytokines and increases anti-inflammatory cytokines associated with the TLR4 pathway. Therefore, miR-451a may be partially responsible for immunomodulatory effects of adipose tissue-derived BiNPs. Full article

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21 pages, 2094 KiB

Open AccessReview

Topical Administration of Drugs Incorporated in Carriers Containing Phospholipid Soft Vesicles for the Treatment of Skin Medical Conditions

by Elka Touitou and Hiba Natsheh

Pharmaceutics 2021, 13(12), 2129; https://doi.org/10.3390/pharmaceutics13122129 - 10 Dec 2021

Cited by 20 | Viewed by 5504

Abstract

This review focuses on the improved topical treatment of various medical skin conditions by the use of drugs delivered from carriers containing phospholipid soft vesicles. Topical drug delivery has many advantages over other ways of administration, having increased patient compliance, avoiding the first-pass [...] Read more.

This review focuses on the improved topical treatment of various medical skin conditions by the use of drugs delivered from carriers containing phospholipid soft vesicles. Topical drug delivery has many advantages over other ways of administration, having increased patient compliance, avoiding the first-pass effect following oral drug administration or not requesting multiple doses administration. However, the skin barrier prevents the access of the applied drug, affecting its therapeutic activity. Carriers containing phospholipid soft vesicles are a new approach to enhance drug delivery into the skin and to improve the treatment outcome. These vesicles contain molecules that have the property to fluidize the phospholipid bilayers generating the soft vesicle and allowing it to penetrate into the deep skin layers. Ethosomes, glycerosomes and transethosomes are soft vesicles containing ethanol, glycerol or a mixture of ethanol and a surfactant, respectively. We review a large number of publications on the research carried out in vitro, in vivo in animal models and in humans in clinical studies, with compositions containing various active molecules for treatment of skin medical conditions including skin infections, skin inflammation, psoriasis, skin cancer, acne vulgaris, hair loss, psoriasis and skin aging. Full article

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35 pages, 3911 KiB

Open AccessReview

mRNA, a Revolution in Biomedicine

by Bruno Baptista, Rita Carapito, Nabila Laroui, Chantal Pichon and Fani Sousa

Pharmaceutics 2021, 13(12), 2090; https://doi.org/10.3390/pharmaceutics13122090 - 5 Dec 2021

Cited by 25 | Viewed by 7678

Abstract

The perspective of using messenger RNA (mRNA) as a therapeutic molecule first faced some uncertainties due to concerns about its instability and the feasibility of large-scale production. Today, given technological advances and deeper biomolecular knowledge, these issues have started to be addressed and [...] Read more.

The perspective of using messenger RNA (mRNA) as a therapeutic molecule first faced some uncertainties due to concerns about its instability and the feasibility of large-scale production. Today, given technological advances and deeper biomolecular knowledge, these issues have started to be addressed and some strategies are being exploited to overcome the limitations. Thus, the potential of mRNA has become increasingly recognized for the development of new innovative therapeutics, envisioning its application in immunotherapy, regenerative medicine, vaccination, and gene editing. Nonetheless, to fully potentiate mRNA therapeutic application, its efficient production, stabilization and delivery into the target cells are required. In recent years, intensive research has been carried out in this field in order to bring new and effective solutions towards the stabilization and delivery of mRNA. Presently, the therapeutic potential of mRNA is undoubtedly recognized, which was greatly reinforced by the results achieved in the battle against the COVID-19 pandemic, but there are still some issues that need to be improved, which are critically discussed in this review. Full article

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16 pages, 6755 KiB

Open AccessArticle

Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics

by Sabna Kotta, Hibah Mubarak Aldawsari, Shaimaa M. Badr-Eldin, Lenah S. Binmahfouz, Rana Bakur Bakhaidar, Nagaraja Sreeharsha, Anroop B. Nair and Chandramouli Ramnarayanan

Pharmaceutics 2021, 13(11), 1851; https://doi.org/10.3390/pharmaceutics13111851 - 3 Nov 2021

Cited by 18 | Viewed by 4161

Abstract

Excessive architectural re-modeling of tissues in pulmonary fibrosis due to proliferation of myofibroblasts and deposition of extracellular matrix adversely affects the elasticity of the alveoli and lung function. Progressively destructive chronic inflammatory disease, therefore, necessitates safe and effective non-invasive airway delivery that can [...] Read more.

Excessive architectural re-modeling of tissues in pulmonary fibrosis due to proliferation of myofibroblasts and deposition of extracellular matrix adversely affects the elasticity of the alveoli and lung function. Progressively destructive chronic inflammatory disease, therefore, necessitates safe and effective non-invasive airway delivery that can reach deep alveoli, restore the surfactant function and reduce oxidative stress. We designed an endogenous surfactant-based liposomal delivery system of naringin to be delivered as an aerosol that supports pulmonary mechanics for the management of pulmonary fibrosis. Phosphatidylcholine-based liposomes showed 91.5 ± 2.4% encapsulation of naringin, with a mean size of 171.4 ± 5.8 nm and zeta potential of −15.5 ± 1.3 mV. Liposomes with the unilamellar structure were found to be spherical and homogeneous in shape using electron microscope imaging. The formulation showed surface tension of 32.6 ± 0.96 mN/m and was able to maintain airway patency of 97 ± 2.5% for a 120 s test period ensuring the effective opening of lung capillaries and deep lung delivery. In vitro lung deposition utilizing Twin Stage Impinger showed 79 ± 1.5% deposition in lower airways, and Anderson Cascade Impactor deposition revealed a mass median aerodynamic diameter of 2.35 ± 1.02 μm for the aerosolized formulation. In vivo efficacy of the developed formulation was analyzed in bleomycin-induced lung fibrosis model in rats after administration by the inhalation route. Lactate dehydrogenase activity, total protein content, and inflammatory cell infiltration in broncho-alveolar lavage fluid were substantially reduced by liposomal naringin. Oxidative stress was minimized as observed from levels of antioxidant enzymes. Masson’s Trichrome staining of lung tissue revealed significant amelioration of histological changes and lesser deposition of collagen. Overall results indicated the therapeutic potential of the developed non-invasive aerosol formulation for the effective management of pulmonary fibrosis. Full article

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12 pages, 1581 KiB

Open AccessArticle

Impact of Compression Force on Mechanical, Textural, Release and Chewing Perception Properties of Compressible Medicated Chewing Gums

by Yuliia Maslii, Tetiana Kolisnyk, Olena Ruban, Olga Yevtifieieva, Svitlana Gureyeva, Andriy Goy, Giedre Kasparaviciene, Zenona Kalveniene and Jurga Bernatoniene

Pharmaceutics 2021, 13(11), 1808; https://doi.org/10.3390/pharmaceutics13111808 - 29 Oct 2021

Cited by 8 | Viewed by 3113

Abstract

Medicated chewing gums (MCGs) represent a beneficial platform for realizing drugs intended for dental prophylaxis and treatment. The present study aimed to investigate the impact of compression force on the mechanical, textural, release, and chewing perception characteristics of compressible MCGs with the combination [...] Read more.

Medicated chewing gums (MCGs) represent a beneficial platform for realizing drugs intended for dental prophylaxis and treatment. The present study aimed to investigate the impact of compression force on the mechanical, textural, release, and chewing perception characteristics of compressible MCGs with the combination of lysozyme hydrochloride (LH) and ascorbic acid (AsA). Four batches of MCGs were obtained on a laboratory single-punch tablet machine applying different forces, i.e., 5, 7, 10, and 15 kN, and evaluated by their geometrical parameters, mechanical resistance, surface and internal structure characteristics, texture profile, release behavior, and perception attributes during mastication. It was found that increasing compression force slightly affected resistance to crushing and friability of MCGs, but resulted in surface smoothing and formation of a thicker layer with highly compacted particle arrangement. According to the texture analysis, increasing compression force led to harder and more adhesive gums, indicating possible difficulties in chewing and, therefore, impairment of their consumer properties. Lower compression forces were also found to be preferable in terms of better drug release from the obtained chewing gums. The volunteers’ assessment showed that an increase of compression force led to significantly raising the initial hardness and crumbliness as well as to decreasing the rate of the integral gum mass formation during mastication, which may negatively affect perceptive sensations when using MCGs. Based on the results obtained, the optimal compressing force was selected to be 7 kN, which allows obtaining MCGs with good organoleptic, mechanical, textural, and release properties. Full article

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23 pages, 3364 KiB

Open AccessArticle

Bactericidal Activity of Non-Cytotoxic Cationic Nanoparticles against Clinically and Environmentally Relevant Pseudomonas spp. Isolates

by Anna Maria Schito, Gabriella Piatti, Debora Caviglia, Guendalina Zuccari, Alessia Zorzoli, Danilo Marimpietri and Silvana Alfei

Pharmaceutics 2021, 13(9), 1411; https://doi.org/10.3390/pharmaceutics13091411 - 6 Sep 2021

Cited by 17 | Viewed by 2882

Abstract

Difficult-to-treat bacterial infections caused by resistant human and plant pathogens severely afflict hospitals, and concern the agri-food sectors. Bacteria from the Pseudomonadaceae family, such as P. aeruginosa, P. putida, P. fluorescens, and P. straminea, can be responsible for severe nosocomial infections in humans. [...] Read more.

Difficult-to-treat bacterial infections caused by resistant human and plant pathogens severely afflict hospitals, and concern the agri-food sectors. Bacteria from the Pseudomonadaceae family, such as P. aeruginosa, P. putida, P. fluorescens, and P. straminea, can be responsible for severe nosocomial infections in humans. P. fragi is the major cause of dairy and meat spoilage, while P. syringae can infect a wide range of economically important plant species, including tobacco, kiwi, and tomato. Therefore, a cationic water-soluble lysine dendrimer (G5-PDK) was tested on several species of Pseudomonas genus. Interestingly, G5-PDK demonstrated variable minimum inhibitory concentrations (MICs), depending on their pigment production, on Pseudomonas aeruginosa (1.6-> 6.4 µM), MICs = 3.2–6.4 µM on P. putida clinical isolates producing pyoverdine, and very low MICs (0.2–1.6 µM) on strains that produced non-pigmented colonies. Time-kill experiments established the rapid bactericidal activity of G5-PDK. In the cytotoxicity experiments on human keratinocytes, after 4 h of treatment with G5-PDK at concentrations 16–500 × MIC, more than 80% of viable cells were observed, and after 24 h, the selectivity indices were maintained above the maximum value reported as acceptable. Due to its proven bactericidal potency and low cytotoxicity, G5-PDK should be seriously considered to counteract clinically and environmentally relevant Pseudomonas isolates. Full article

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16 pages, 2331 KiB

Open AccessArticle

Development of Chitosan/Cyclodextrin Nanospheres for Levofloxacin Ocular Delivery

by Federica De Gaetano, Andreana Marino, Alessia Marchetta, Corrado Bongiorno, Roberto Zagami, Maria C. Cristiano, Donatella Paolino, Venerando Pistarà and Cinzia A. Ventura

Pharmaceutics 2021, 13(8), 1293; https://doi.org/10.3390/pharmaceutics13081293 - 19 Aug 2021

Cited by 29 | Viewed by 3774

Abstract

Levofloxacin (LVF) is an antibacterial drug approved for the treatment of ocular infections. However, due to the low ocular bioavailability, high doses are needed, causing bacterial resistance. Polymeric nanospheres (NPs) loading antibiotic drugs represent the most promising approach to eradicate ocular infections and [...] Read more.

Levofloxacin (LVF) is an antibacterial drug approved for the treatment of ocular infections. However, due to the low ocular bioavailability, high doses are needed, causing bacterial resistance. Polymeric nanospheres (NPs) loading antibiotic drugs represent the most promising approach to eradicate ocular infections and to treat pathogen resistance. In this study, we have developed chitosan NPs based on sulfobutyl-ether-β-cyclodextrin (CH/SBE-β-CD NPs) for ocular delivery of LVF. CH/SBE-β-CD NPs loading LVF were characterized in terms of encapsulation parameters, morphology, and sizes, in comparison to NPs produced without the macrocycle. Nuclear magnetic resonance and UV–vis spectroscopy studies demonstrated that SBE-β-CD is able to complex LVF and to influence encapsulation parameters of NPs, producing high encapsulation efficiency and LVF loading. The NPs were homogenous in size, with a hydrodynamic radius between 80 and 170 nm and positive zeta potential (ζ) values. This surface property could promote the interaction of NPs with the negatively charged ocular tissue, increasing their residence time and, consequently, LVF efficacy. In vitro, antibacterial activity against Gram-positive and Gram-negative bacteria showed a double higher activity of CH/SBE-β-CD NPs loading LVF compared to the free drug, suggesting that chitosan NPs based on SBE-β-CD could be a useful system for the treatment of ocular infections. Full article

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37 pages, 74648 KiB

Open AccessArticle

Synthesis, Physicochemical Characterization, In Vitro 2D/3D Human Cell Culture, and In Vitro Aerosol Dispersion Performance of Advanced Spray Dried and Co-Spray Dried Angiotensin (1—7) Peptide and PNA5 with Trehalose as Microparticles/Nanoparticles for Targeted Respiratory Delivery as Dry Powder Inhalers

by Wafaa Alabsi, Maria F. Acosta, Fahad A. Al-Obeidi, Meredith Hay, Robin Polt and Heidi M. Mansour

Pharmaceutics 2021, 13(8), 1278; https://doi.org/10.3390/pharmaceutics13081278 - 17 Aug 2021

Cited by 11 | Viewed by 4868

Abstract

The peptide hormone Angiotensin (1—7), Ang (1—7) or (Asp-Arg-Val-Tyr-Ile-His-Pro), is an essential component of the renin–angiotensin system (RAS) peripherally and is an agonist of the Mas receptor centrally. Activation of this receptor in the CNS stimulates various biological activities that make the Ang [...] Read more.

The peptide hormone Angiotensin (1—7), Ang (1—7) or (Asp-Arg-Val-Tyr-Ile-His-Pro), is an essential component of the renin–angiotensin system (RAS) peripherally and is an agonist of the Mas receptor centrally. Activation of this receptor in the CNS stimulates various biological activities that make the Ang (1—7)/MAS axis a novel therapeutic approach for the treatment of many diseases. The related O-linked glycopeptide, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-β-D-Glc)-amide (PNA5), is a biousian revision of the native peptide hormone Ang (1—7) and shows enhanced stability in vivo and greater levels of brain penetration. We have synthesized the native Ang (1—7) peptide and the glycopeptide, PNA5, and have formulated them for targeted respiratory delivery as inhalable dry powders. Solid phase peptide synthesis (SPPS) successfully produced Ang (1—7) and PNA5. Measurements of solubility and lipophilicity of raw Ang (1—7) and raw PNA5 using experimental and computational approaches confirmed that both the peptide and glycopeptide have high-water solubility and are amphipathic. Advanced organic solution spray drying was used to engineer the particles and produce spray-dried powders (SD) of both the peptide and the glycopeptide, as well as co-spray-dried powders (co-SD) with the non-reducing sugar and pharmaceutical excipient, trehalose. The native peptide, glycopeptide, SD, and co-SD powders were comprehensively characterized, and exhibited distinct glass transitions (T_g) consistent with the amorphous glassy state formation with T_gs that are compatible with use in vivo. The homogeneous particles displayed small sizes in the nanometer size range and low residual water content in the solid-state. Excellent aerosol dispersion performance with a human DPI device was demonstrated. In vitro human cell viability assays showed that Ang (1—7) and PNA5 are biocompatible and safe for different human respiratory and brain cells. Full article

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18 pages, 3288 KiB

Open AccessArticle

Photodegradation of Bexarotene and Its Implication for Cytotoxicity

by Agata Kryczyk-Poprawa, István Zupkó, Péter Bérdi, Paweł Żmudzki, Joanna Piotrowska, Elżbieta Pękala, Aleksandra Berdys, Bożena Muszyńska and Włodzimierz Opoka

Pharmaceutics 2021, 13(8), 1220; https://doi.org/10.3390/pharmaceutics13081220 - 7 Aug 2021

Cited by 3 | Viewed by 3009

Abstract

A detailed understanding of the stability of an active pharmaceutical ingredient and a pharmaceutical dosage form is essential for the drug-development process and for safe and effective use of medicines. Photostability testing as an inherent part of stability studies provides valuable knowledge on [...] Read more.

A detailed understanding of the stability of an active pharmaceutical ingredient and a pharmaceutical dosage form is essential for the drug-development process and for safe and effective use of medicines. Photostability testing as an inherent part of stability studies provides valuable knowledge on degradation pathways and structures of products generated under UV irradiation. Photostability is particularly important for topically administered drugs, as they are more exposed to UV radiation. Bexarotene is a more recent third-generation retinoid approved by the U.S. Food and Drug Administration and the European Medicines Agency as a topically applied anticancer agent. The present study aimed to assess bexarotene photostability, including the presence of UV filters, which have been permitted to be used in cosmetic products in Europe and the USA. The bexarotene photostability testing was performed in ethanol solutions and in formulations applied on PMMA plates. The UPLC-MS/MS technique was used to determine the tested substance. The presence of photocatalysts such as TiO₂ or ZnO, as well as the organic UV filters avobenzone, benzophenone-3, meradimate, and homosalate, could contribute to degradation of bexarotene under UV irradiation. Four photocatalytic degradation products of bexarotene were identified for the first time. The antiproliferative properties of the degradation products of bexarotene were assessed by MTT assay on a panel of human adherent cancer cells, and concentration-dependent growth inhibition was evidenced on all tested cell lines. The cytotoxicity of the formed products after 4 h of UV irradiation was significantly higher than that of the parent compound (p < 0.05). Furthermore non-cancerous murine fibroblasts exhibited marked concentration-dependent inhibition by bexarotene, while the degradation products elicited more pronounced antiproliferative action only at the highest applied concentration. Full article

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22 pages, 3944 KiB

Open AccessArticle

Increased Water-Solubility and Maintained Antioxidant Power of Resveratrol by Its Encapsulation in Vitamin E TPGS Micelles: A Potential Nutritional Supplement for Chronic Liver Disease

by Guendalina Zuccari, Silvana Alfei, Alessia Zorzoli, Danilo Marimpietri, Federica Turrini, Sara Baldassari, Leonardo Marchitto and Gabriele Caviglioli

Pharmaceutics 2021, 13(8), 1128; https://doi.org/10.3390/pharmaceutics13081128 - 23 Jul 2021

Cited by 28 | Viewed by 6491

Abstract

Children affected by chronic liver disease exhibit impaired neurocognitive development and growth due to the low absorption and digestion of nutrients. Furthermore, malnutrition is an adverse prognostic factor in liver transplantation as it is associated with an increase in morbidity and mortality. D-α-tocopheryl-polyethylene-glycol-succinate [...] Read more.

Children affected by chronic liver disease exhibit impaired neurocognitive development and growth due to the low absorption and digestion of nutrients. Furthermore, malnutrition is an adverse prognostic factor in liver transplantation as it is associated with an increase in morbidity and mortality. D-α-tocopheryl-polyethylene-glycol-succinate (TPGS) is currently administered per os as a vitamin E source to improve children’s survival and well-being; however, TPGS alone does not reverse spinocerebellar degeneration and lipid peroxidation. To potentiate the effects of TPGS, we loaded micelles with resveratrol (RES), a natural polyphenol, with antioxidant and antiinflammatory activities, which has demonstrated protective action in the liver. Firstly, we investigated the suitability of TPGS to encapsulate RES in micelles by means of a phase-solubility study, then RES-TPGS formulations were prepared via solvent casting and solvent diffusion evaporation methods. RES-TPGS colloidal dispersions showed small mean diameters (12 nm), low polydispersity, and quite neutral Zeta potentials. The formulations showed a sustained drug release and a good drug loading capacity, further confirmed by infrared spectroscopy and differential scanning calorimetry. RES-TPGSs exhibited unaltered antioxidant activity compared to pristine RES via the DPPH assay and a significant reduction in toxicity compared to empty TPGS on HaCaT cells. Thus, RES-TPGS micelles may overcome the challenges of current liver disease therapy by providing more protective effects thanks to the antioxidant activity of RES and by reducing the surfactant toxicity on normal cells. Full article

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10 pages, 1141 KiB

Open AccessArticle

Pre-Drawn Syringes of Comirnaty for an Efficient COVID-19 Mass Vaccination: Demonstration of Stability

by Francesca Selmin, Umberto M. Musazzi, Silvia Franzè, Edoardo Scarpa, Loris Rizzello, Patrizia Procacci and Paola Minghetti

Pharmaceutics 2021, 13(7), 1029; https://doi.org/10.3390/pharmaceutics13071029 - 7 Jul 2021

Cited by 14 | Viewed by 5718

Abstract

Moving towards a real mass vaccination in the context of COVID-19, healthcare professionals are required to face some criticisms due to limited data on the stability of a mRNA-based vaccine (Pfizer-BioNTech COVID-19 Vaccine in the US or Comirnaty in EU) as a dose [...] Read more.

Moving towards a real mass vaccination in the context of COVID-19, healthcare professionals are required to face some criticisms due to limited data on the stability of a mRNA-based vaccine (Pfizer-BioNTech COVID-19 Vaccine in the US or Comirnaty in EU) as a dose in a 1 mL-syringe. The stability of the lipid nanoparticles and the encapsulated mRNA was evaluated in a “real-life” scenario. Specifically, we investigated the effects of different storing materials (e.g., syringes vs. glass vials), as well as of temperature and mechanical stress on nucleic acid integrity, number, and particle size distribution of lipid nanoparticles. After 5 h in the syringe, lipid nanoparticles maintained the regular round shape, and the hydrodynamic diameter ranged between 80 and 100 nm with a relatively narrow polydispersity (<0.2). Samples were stable independently of syringe materials and storage conditions. Only strong mechanical stress (e.g., shaking) caused massive aggregation of lipid nanoparticles and mRNA degradation. These proof-of-concept experiments support the hypothesis that vaccine doses can be safely prepared in a dedicated area using an aseptic technique and transferred without affecting their stability. Full article

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23 pages, 3142 KiB

Open AccessArticle

Ophthalmic In Situ Gels with Balsam Poplar Buds Extract: Formulation, Rheological Characterization, and Quality Evaluation

by Monika Stanciauskaite, Mindaugas Marksa, Liudas Ivanauskas, Kristina Perminaite and Kristina Ramanauskiene

Pharmaceutics 2021, 13(7), 953; https://doi.org/10.3390/pharmaceutics13070953 - 24 Jun 2021

Cited by 13 | Viewed by 3494

Abstract

Balsam poplar buds are a raw material with a high content of polyphenols. Various polyphenols are known for their anti-inflammatory and antioxidant properties. In this study, an aqueous extract of balsam poplar buds was prepared in order to use environmentally friendly and non-aggressive [...] Read more.

Balsam poplar buds are a raw material with a high content of polyphenols. Various polyphenols are known for their anti-inflammatory and antioxidant properties. In this study, an aqueous extract of balsam poplar buds was prepared in order to use environmentally friendly and non-aggressive solvents. The aqueous extract was lyophilized, and a 1% aqueous solution of lyophilized balsam poplar buds extract (L1) was prepared. L1 solution was used as a source of polyphenols for the production of ophthalmic in situ gels, so as to develop a product featuring antioxidant properties. Poloxamer 407 (P407) and hydroxypropyl methylcellulose (HPMC) were selected as gelling agents for the in situ gels. In order to select the formulations with the best conditions of use, formulations of different polymer concentrations (P407—10%, 12%, 15%; HPMC—0.5%, 0.75%) were prepared, choosing the same amount of the active polyphenol source L1. The physicochemical properties, rheological parameters, stability, and irritant effect on the rabbit corneal cell line (SIRC) were evaluated. Formulations in which P407 and HMPC concentrations were 10/0.75% and 12%/0.75% reached a gelation point close to the ocular surface temperature; the gels remained stable for 30 days and did not cause an irritant effect on the SIRC cell line. Full article

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16 pages, 2869 KiB

Open AccessArticle

Effect of Protoberberine-Rich Fraction of Chelidonium majus L. on Endometriosis Regression

by Alicja Warowicka, Badr Qasem, Anna Dera-Szymanowska, Maria Wołuń-Cholewa, Patryk Florczak, Nikodem Horst, Marta Napierała, Krzysztof Szymanowski, Łukasz Popenda, Grażyna Bartkowiak, Ewa Florek, Anna Goździcka-Józefiak and Piotr Młynarz

Pharmaceutics 2021, 13(7), 931; https://doi.org/10.3390/pharmaceutics13070931 - 23 Jun 2021

Cited by 7 | Viewed by 3716

Abstract

Endometriosis is a gynecological disease defined by the presence of endometrial tissue outside the uterus. To date, the effective treatment of this disease is still based on invasive surgery or laparoscopy. Chelidonium majus L. (Papaveraceae) belongs to medicinal, latex-bearing plants. Extracts from the [...] Read more.

Endometriosis is a gynecological disease defined by the presence of endometrial tissue outside the uterus. To date, the effective treatment of this disease is still based on invasive surgery or laparoscopy. Chelidonium majus L. (Papaveraceae) belongs to medicinal, latex-bearing plants. Extracts from the plant are a rich source of pharmacologically active agents. Protoberberine compounds derived from C. majus possess anticancer and antiproliferative activities. In the present study of a rat model of endometriosis, we investigated the influence of the plant protoberberine-rich fraction (BBR) obtained from the medicinal plant C. majus on the development of endometriosis. To understand of BBR therapeutic potential for endometriosis, metabolomics has been applied to study. BBR was prepared from an ethanolic extract of dry plants C. majus. Rats (n = 16) with confirmed endometriosis were treated with BBR administered orally (1 g/kg) for 14 days. Blood serum samples were collected from all of the animals and metabolites were studied using the NMR method. The metabolomic pattern was compared before and after the protoberberine treatment. The performed analysis showed significant changes in the concentrations of metabolites that are involved in energy homeostasis, including glucose, glutamine, and lactate. Histopathological studies showed no recurrence of endometriosis loci after treatment with BBR. The results of the study found that BBR treatment prevents the recurrence of endometriosis in rats. Moreover, metabolomics profiling can be applied to better understand the mechanisms of action of these protoberberine secondary plant metabolites. Our findings provide new insights into the pharmaceutical activity of natural protoberberine plant compounds. Full article

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13 pages, 11408 KiB

Open AccessArticle

Studying the Impact of the Temperature and Sorbed Water during Microwave-Induced In Situ Amorphization: A Case Study of Celecoxib and Polyvinylpyrrolidone

by Nele-Johanna Hempel, Matthias M. Knopp, Korbinian Löbmann and Ragna Berthelsen

Pharmaceutics 2021, 13(6), 886; https://doi.org/10.3390/pharmaceutics13060886 - 15 Jun 2021

Cited by 3 | Viewed by 2610

Abstract

Microwave-induced in situ amorphization of a drug into a polymeric amorphous solid dispersion (ASD) has been suggested to follow a dissolution process of the drug into the polymeric network, at temperatures above the glass transition temperature (T_g) of the polymer. [...] Read more.

Microwave-induced in situ amorphization of a drug into a polymeric amorphous solid dispersion (ASD) has been suggested to follow a dissolution process of the drug into the polymeric network, at temperatures above the glass transition temperature (T_g) of the polymer. Thus, increasing the compact temperature, above the T_g of the polymer, is expected to increase the rate of drug dissolution in the mobile polymer, i.e., the rate of amorphization, in a direct proportional fashion. To test this hypothesis, the present study aimed at establishing a linear correlation between the compact temperature and the rate of drug amorphization using celecoxib (CCX) and the polymers polyvinylpyrrolidone (PVP) 12 and PVP17 as the model systems. Water sorbed into the drug–polymer compacts during 2 weeks of storage at 75% relative humidity was used as the dielectric heating source for the present drug amorphization process, and therefore directly affected the compact temperature during exposure to microwave radiation; the loss of water during heating was also studied. For this, compacts prepared with 30 wt% CCX, 69.5 wt% PVP12 or PVP17 and 0.5 wt% magnesium stearate (lubricant) were conditioned to have a final water content of approx. 20 wt%. The conditioned compacts were exposed to microwave radiation for 10 min at variable power outputs to achieve different compact temperatures. For compacts containing CCX in both PVP12 and PVP17, a linear correlation was established between the measured compact end temperature and the rate of drug amorphization during 10 min of exposure to microwave radiation. For compacts containing CCX in PVP12, a fully amorphous ASD was obtained after 10 min of exposure to microwave radiation with a measured compact end temperature of 71 °C. For compacts containing CCX in PVP17, it was not possible to obtain a fully amorphous ASD. The reason for this is most likely that a fast evaporation of the sorbed water increased the T_g of the conditioned drug–polymer compacts to temperatures above the highest reachable compact temperature during exposure to microwave radiation in the utilized experimental setup. Supporting this conclusion, evaporation of the sorbed water was observed to be faster for compacts containing PVP17 compared to compacts containing PVP12. Full article

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18 pages, 2169 KiB

Open AccessArticle

Development of Innovative Chewable Gel Tablets Containing Nutmeg Essential Oil Microcapsules and Their Physical Properties Evaluation

by Inga Matulyte, Mindaugas Marksa and Jurga Bernatoniene

Pharmaceutics 2021, 13(6), 873; https://doi.org/10.3390/pharmaceutics13060873 - 12 Jun 2021

Cited by 10 | Viewed by 4251

Abstract

Chewable gel tablets are a dosed pharmaceutical form, which can have an active substance, pharmacological effect, or value of nutrition. The texture of these tablets is soft, springy, flexible, and elastic—this is influenced by the chosen ingredients. The aim of this study was [...] Read more.

Chewable gel tablets are a dosed pharmaceutical form, which can have an active substance, pharmacological effect, or value of nutrition. The texture of these tablets is soft, springy, flexible, and elastic—this is influenced by the chosen ingredients. The aim of this study was to prepare chewable gel tablets with nutmeg essential oil-loaded microcapsules and determine the volatile compounds released from this pharmaceutical form. Gel tablets were prepared by using gelatin as basis, nutmeg essential oil as active compound, and natural ingredients: thyme-sugar syrup, thyme extract, and citric acid as taste and color additives. Texture properties were measured by a texture analyzer. The release of volatile compounds from nutmeg essential oil and gel tablets were analyzed by headspace-gas chromatography with mass spectroscopy in control and artificial saliva conditions in vitro. Nutmeg essential oil microcapsules had influence on the gel tablet’s physical properties (p < 0.05, by comparing tablets without glycerol and relative sample with glycerol); glycerol protects the tablets from the formation of sugar crystals on top and keeps good physical parameters (p < 0.05). A total of 12 volatile compounds were identified in nutmeg essential oil, and the six compounds with the highest amounts were selected as controls. Gel tablets prolong the release time of volatile compounds and reduce the amount of the compounds compared to the microcapsules (p < 0.05). Full article

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19 pages, 3286 KiB

Open AccessArticle

Translational Studies on the Potential of a VEGF Nanoparticle-Loaded Hyaluronic Acid Hydrogel

by Joanne O’Dwyer, Robert Murphy, Arlyng González-Vázquez, Lenka Kovarova, Martin Pravda, Vladimir Velebny, Andreas Heise, Garry P. Duffy and Sally Ann Cryan

Pharmaceutics 2021, 13(6), 779; https://doi.org/10.3390/pharmaceutics13060779 - 22 May 2021

Cited by 12 | Viewed by 3993

Abstract

Heart failure has a five-year mortality rate approaching 50%. Inducing angiogenesis following a myocardial infarction is hypothesized to reduce cardiomyocyte death and tissue damage, thereby preventing heart failure. Herein, a novel nano-in-gel delivery system for vascular endothelial growth factor (VEGF), composed of star-shaped [...] Read more.

Heart failure has a five-year mortality rate approaching 50%. Inducing angiogenesis following a myocardial infarction is hypothesized to reduce cardiomyocyte death and tissue damage, thereby preventing heart failure. Herein, a novel nano-in-gel delivery system for vascular endothelial growth factor (VEGF), composed of star-shaped polyglutamic acid-VEGF nanoparticles in a tyramine-modified hyaluronic acid hydrogel (nano-VEGF-HA-TA), is investigated. The ability of the nano-VEGF-HA-TA system to induce angiogenesis is assessed in vivo using a chick chorioallantoic membrane model (CAM). The formulation is then integrated with a custom-made, clinically relevant catheter suitable for minimally invasive endocardial delivery and the effect of injection on hydrogel properties is examined. Nano-VEGF-HA-TA is biocompatible on a CAM assay and significantly improves blood vessel branching (p < 0.05) and number (p < 0.05) compared to a HA-TA hydrogel without VEGF. Nano-VEGF-HA-TA is successfully injected through a 1.2 m catheter, without blocking or breaking the catheter and releases VEGF for 42 days following injection in vitro. The released VEGF retains its bioactivity, significantly improving total tubule length on a Matrigel^® assay and human umbilical vein endothelial cell migration on a Transwell^® migration assay. This VEGF-nano in a HA-TA hydrogel delivery system is successfully integrated with an appropriate device for clinical use, demonstrates promising angiogenic properties in vivo and is suitable for further clinical translation. Full article

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17 pages, 2141 KiB

Open AccessArticle

Novel Extraction Method Using Excipients to Enhance Yield of Genistein and Daidzein in Trifolium pratensis L.

by Jurga Andreja Kazlauskaite, Liudas Ivanauskas and Jurga Bernatoniene

Pharmaceutics 2021, 13(6), 777; https://doi.org/10.3390/pharmaceutics13060777 - 22 May 2021

Cited by 11 | Viewed by 2899

Abstract

Isoflavones can be found in different chemical forms, but the health beneficial effects mainly appear in their free forms—aglycones. Their yield in red clover (Trifolium pratensis L.) extracts differs due to different extraction and hydrolysis methodologies. The main aim of this study [...] Read more.

Isoflavones can be found in different chemical forms, but the health beneficial effects mainly appear in their free forms—aglycones. Their yield in red clover (Trifolium pratensis L.) extracts differs due to different extraction and hydrolysis methodologies. The main aim of this study was to obtain the highest yields of daidzein and genistein from red clover blossoms through the various extraction and hydrolysis methods and to increase their quantities using additional excipients. Extracts were obtained by ultrasound-assisted, heat-reflux and maceration methods combining them with acidic, alkaline, and thermal hydrolysis. Using ultrasound-assisted extraction with optimal conditions and heat-reflux method highest yields of isoflavones were obtained in UTE510 (393.23 ± 19.66 µg/g daidzein and 171.57 ± 8.58 µg/g genistein); UTE530 (415.07 ± 20.75 µg/g daidzein and 150.57 ± 7.53 µg/g genistein) and HNE5 (432.30 ± 21.61 µg/g daidzein and 154.50 ± 7.72 µg/g genistein) samples. These conditions were used with excipients: magnesium aluminometasilicate, croscarmellose sodium, sodium carboxymethyl starch and vinylpyrrolidone-vinyl acetate copolymer. This is the first study reporting the ability of the vinylpyrrolidone-vinyl acetate copolymer to promote solubilization and availability of active compounds from a herbal extract, resulting in enhanced isoflavones yield. The results of the present study showing increased solubility and availability provided by the vinylpyrrolidone-vinyl acetate copolymer suggest that this preparation could in principle also reduce variability due to limited water solubility of isoflavones. Full article

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23 pages, 4093 KiB

Open AccessArticle

Toxicokinetic/Toxicodynamic Interaction Studies in Rats between the Drugs of Abuse γ-Hydroxybutyric Acid and Ketamine and Treatment Strategies for Overdose

by Nisha V. Kwatra and Marilyn E. Morris

Pharmaceutics 2021, 13(5), 741; https://doi.org/10.3390/pharmaceutics13050741 - 18 May 2021

Cited by 2 | Viewed by 3708

Abstract

γ-hydroxybutyric acid (GHB) is widely abused alone and in combination with other club drugs such as ketamine. GHB exhibits nonlinear toxicokinetics, characterized by saturable metabolism, saturable absorption and saturable renal reabsorption mediated by monocarboxylate transporters (MCTs). In this research, we characterized the effects [...] Read more.

γ-hydroxybutyric acid (GHB) is widely abused alone and in combination with other club drugs such as ketamine. GHB exhibits nonlinear toxicokinetics, characterized by saturable metabolism, saturable absorption and saturable renal reabsorption mediated by monocarboxylate transporters (MCTs). In this research, we characterized the effects of ketamine on GHB toxicokinetics/toxicodynamics (TK/TD) and evaluated the use of MCT inhibition and specific receptor antagonism as potential treatment strategies for GHB overdose in the presence of ketamine. Adult male Sprague-Dawley rats were administered GHB 600 mg/kg i.v. alone or with ketamine (6 mg/kg i.v. bolus plus 1 mg/kg/min i.v. infusion). Plasma and urine samples were collected and respiratory parameters (breathing frequency, tidal and minute volume) continuously monitored using whole-body plethysmography. Ketamine co-administration resulted in a significant decrease in GHB total and metabolic clearance, with renal clearance remaining unchanged. Ketamine prevented the compensatory increase in tidal volume produced by GHB, and this resulted in a significant decline in minute volume when compared to GHB alone. Sleep time and lethality were also increased after ketamine co-administration when compared to GHB. L-lactate and AR-C155858 (potent MCT inhibitor) treatment resulted in an increase in GHB renal and total clearance and improvement in respiratory depression. AR-C155858 administration also resulted in a significant decrease in GHB brain/plasma ratio. SCH50911 (GABA_B receptor antagonist), but not naloxone, improved GHB-induced respiratory depression in the presence of ketamine. In conclusion, ketamine ingestion with GHB can result in significant TK/TD interactions. MCT inhibition and GABA_B receptor antagonism can serve as potential treatment strategies for GHB overdose when it is co-ingested with ketamine. Full article

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19 pages, 2730 KiB

Open AccessArticle

Ferulic Acid-Loaded Polymeric Nanoparticles for Potential Ocular Delivery

by Alessia Romeo, Teresa Musumeci, Claudia Carbone, Angela Bonaccorso, Simona Corvo, Gabriella Lupo, Carmelina Daniela Anfuso, Giovanni Puglisi and Rosario Pignatello

Pharmaceutics 2021, 13(5), 687; https://doi.org/10.3390/pharmaceutics13050687 - 11 May 2021

Cited by 29 | Viewed by 4563

Abstract

Ferulic acid (FA) is an antioxidant compound that can prevent ROS-related diseases, but due to its poor solubility, therapeutic efficacy is limited. One strategy to improve the bioavailability is nanomedicine. In the following study, FA delivery through polymeric nanoparticles (NPs) consisting of polylactic [...] Read more.

Ferulic acid (FA) is an antioxidant compound that can prevent ROS-related diseases, but due to its poor solubility, therapeutic efficacy is limited. One strategy to improve the bioavailability is nanomedicine. In the following study, FA delivery through polymeric nanoparticles (NPs) consisting of polylactic acid (NPA) and poly(lactic-co-glycolic acid) (NPB) is proposed. To verify the absence of cytotoxicity of blank carriers, a preliminary in vitro assay was performed on retinal pericytes and endothelial cells. FA-loaded NPs were subjected to purification studies and the physico-hemical properties were analyzed by photon correlation spectroscopy. Encapsulation efficiency and in vitro release studies were assessed through high performance liquid chromatography. To maintain the integrity of the systems, nanoformulations were cryoprotected and freeze-dried. Morphology was evaluated by a scanning electron microscope. Physico-chemical stability of resuspended nanosystems was monitored during 28 days of storage at 5 °C. Thermal analysis and Fourier-transform infrared spectroscopy were performed to characterize drug state in the systems. Results showed homogeneous particle populations, a suitable mean size for ocular delivery, drug loading ranging from 64.86 to 75.16%, and a controlled release profile. The obtained systems could be promising carriers for ocular drug delivery, legitimating further studies on FA-loaded NPs to confirm efficacy and safety in vitro. Full article

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22 pages, 2654 KiB

Open AccessReview

Image Analysis: A Versatile Tool in the Manufacturing and Quality Control of Pharmaceutical Dosage Forms

by Dóra Farkas, Lajos Madarász, Zsombor K. Nagy, István Antal and Nikolett Kállai-Szabó

Pharmaceutics 2021, 13(5), 685; https://doi.org/10.3390/pharmaceutics13050685 - 10 May 2021

Cited by 19 | Viewed by 5807

Abstract

In pharmaceutical sciences, visual inspection is one of the oldest methods used for description in pharmacopeias and is still an important part of the characterization and qualification of active ingredients, excipients, and dosage forms. With the development of technology, it is now also [...] Read more.

In pharmaceutical sciences, visual inspection is one of the oldest methods used for description in pharmacopeias and is still an important part of the characterization and qualification of active ingredients, excipients, and dosage forms. With the development of technology, it is now also possible to take images of various pharmaceutical dosage forms with different imaging methods in a size range that is hardly visible or completely invisible to the human eye. By analyzing high-quality designs, physicochemical processes can be understood, and the results can be used even in the optimization of the composition of the dosage form and in the development of its production. The present study aims to show some of the countless ways image analysis can be used in the manufacturing and quality assessment of different dosage forms. This summary also includes measurements and an evaluation of, amongst others, a less studied dosage form, medicated foams. Full article

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16 pages, 1075 KiB

Open AccessArticle

Novel Self-Nano-Emulsifying Drug Delivery Systems Containing Astaxanthin for Topical Skin Delivery

by Thellie Ponto, Gemma Latter, Giuseppe Luna, Vânia R. Leite-Silva, Anthony Wright and Heather A. E. Benson

Pharmaceutics 2021, 13(5), 649; https://doi.org/10.3390/pharmaceutics13050649 - 3 May 2021

Cited by 24 | Viewed by 5601

Abstract

Astaxanthin (ASX) is a potent lipophilic antioxidant derived from the natural pigment that gives marine animals their distinctive red-orange colour and confers protection from ultraviolet radiation. Self nano-emulsifying drug delivery systems (SNEDDS) have been successfully developed and evaluated to increase the skin penetration [...] Read more.

Astaxanthin (ASX) is a potent lipophilic antioxidant derived from the natural pigment that gives marine animals their distinctive red-orange colour and confers protection from ultraviolet radiation. Self nano-emulsifying drug delivery systems (SNEDDS) have been successfully developed and evaluated to increase the skin penetration of ASX and target its antioxidant and anti-inflammatory potential to the epidermis and dermis. SNEDDS were prepared using a low-temperature spontaneous emulsification method, and their physical characteristics, stability, antioxidant activity, and skin penetration were characterized. Terpenes (D-limonene, geraniol, and farnesol) were included in the SNEDDS formulations to evaluate their potential skin penetration enhancement. An HPLC assay was developed that allowed ASX recovery from skin tissues and quantification. All SNEDDS formulations had droplets in the 20 nm range, with low polydispersity. ASX stability over 28 days storage in light and dark conditions was improved and antioxidant activity was high. SNEDDS-L1 (no terpene) gave significantly increased ASX penetration to the stratum corneum (SC) and the epidermis-dermis-follicle region (E + D + F) compared to an ASX in oil solution and a commercial ASX facial serum product. The SNEDDS-containing D-limonene gave the highest ASX permeation enhancement, with 3.34- and 3.79-fold the amount in the SC and E + D + F, respectively, compared to a similar applied dose of ASX in oil. We concluded that SNEDDS provide an effective formulation strategy for enhanced skin penetration of a highly lipophilic molecule, and when applied to ASX, have the potential to provide topical formulations for UV protection, anti-aging, and inflammatory conditions of the skin. Full article

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14 pages, 2534 KiB

Open AccessArticle

Cyclodextrin-Assisted Extraction Method as a Green Alternative to Increase the Isoflavone Yield from Trifolium pratensis L. Extract

by Jurga Andreja Kazlauskaite, Liudas Ivanauskas and Jurga Bernatoniene

Pharmaceutics 2021, 13(5), 620; https://doi.org/10.3390/pharmaceutics13050620 - 26 Apr 2021

Cited by 17 | Viewed by 2902

Abstract

Trifolium pratense L. is receiving increasing attention due to the isoflavones it contains, which have been studied for their benefits to human health. A common problem with isoflavone aglycones is a rather low water solubility and limited pharmaceutical applications. The use of excipients, [...] Read more.

Trifolium pratense L. is receiving increasing attention due to the isoflavones it contains, which have been studied for their benefits to human health. A common problem with isoflavone aglycones is a rather low water solubility and limited pharmaceutical applications. The use of excipients, such as cyclodextrins in the production of isoflavone rich extracts, could become one of the new strategies for the extraction of target compounds. The aim of this study was to evaluate an eco-friendly method using the effects of α-, β- and γ-cyclodextrins for isoflavone solubilization in plant extracts in comparison to a standard extract without excipients. Extractions of red clover were prepared using ultrasound-assisted combined with thermal hydrolysis and heat reflux. It was determined that cyclodextrins significantly increased the isoflavones aglycone yields. By increasing cyclodextrins in the extraction media from 1 to 5%, the daidzin concentration increased on average by 1.06 (α-cyclodextrins), 1.4 (β-cyclodextrins) and 1.25 (γ-cyclodextrins) times. Genistein concentration increased using α- and γ-cyclodextrins (1.28 and 1.12 times, α- and γ-cyclodextrins, respectively), but decreased using β-cyclodextrins. The results showed that the cyclodextrin-assisted extraction enhanced the yields of isoflavones from red clover, which suggests using cyclodextrins as a green alternative and a cost-effective method to increase its pharmaceutical application. Full article

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16 pages, 1419 KiB

Open AccessArticle

Assessment of Alcohol-Based Hand Sanitizers for Long-Term Use, Formulated with Addition of Natural Ingredients in Comparison to WHO Formulation 1

by Francesca Fallica, Chiara Leonardi, Valeria Toscano, Debora Santonocito, Paola Leonardi and Carmelo Puglia

Pharmaceutics 2021, 13(4), 571; https://doi.org/10.3390/pharmaceutics13040571 - 17 Apr 2021

Cited by 13 | Viewed by 8459

Abstract

During the spread of COVID-19, many laboratories used the “Formulation 1” proposed by the World Health Organization to prepare hand sanitizers. Taking into consideration its ingredients and the prolonged use of hand sanitizers, “Formulation 1” (P1) was compared with [...] Read more.

During the spread of COVID-19, many laboratories used the “Formulation 1” proposed by the World Health Organization to prepare hand sanitizers. Taking into consideration its ingredients and the prolonged use of hand sanitizers, “Formulation 1” (P1) was compared with two gel formulations (P2 and P3) prepared with the addition of natural emollients and two different viscosity enhancers to define their chemical–physical stability, biocidal efficacy, and in vivo acceptability and tolerability. P1 resulted in the most efficient biocide but was poorly tolerated by the skin and not acceptable in volunteer hedonic evaluation, especially in terms of irritation and drying effect, with an expectable reduction in the compliance. Moreover, its liquid formulation is unpractical and can cause ethanol evaporation. P2 and P3 proved to be both good products regarding pH and alcohol strength values. However, in terms of viscosity, texture, ease of use, and application, P3 seemed to be a better gel product than P2. Moreover, they were well tolerated by the skin, increasing the hydration of the stratum corneum, due to the addition of Calendula officinalis and Aloe vera. Despite a lower ethanol concentration than P1, P2 and P3 also showed a good biocide efficiency, with better results in P2. In conclusion, these gel formulations proved to be more convenient for long-term use with a good balance between efficacy, safety, and compatibility with the skin. Full article

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15 pages, 908 KiB

Open AccessArticle

Topical Unsaturated Fatty Acid Vesicles Improve Antioxidant Activity of Ammonium Glycyrrhizinate

by Maria Chiara Cristiano, Antonia Mancuso, Massimo Fresta, Daniele Torella, Federica De Gaetano, Cinzia Anna Ventura and Donatella Paolino

Pharmaceutics 2021, 13(4), 548; https://doi.org/10.3390/pharmaceutics13040548 - 14 Apr 2021

Cited by 21 | Viewed by 2825

Abstract

Linoleic and oleic acids are natural unsaturated fatty acids involved in several biological processes and recently studied as structural components of innovative nanovesicles. The use of natural components in the pharmaceutical field is receiving growing attention from the scientific world. The aim of [...] Read more.

Linoleic and oleic acids are natural unsaturated fatty acids involved in several biological processes and recently studied as structural components of innovative nanovesicles. The use of natural components in the pharmaceutical field is receiving growing attention from the scientific world. The aim of this research work is to design, to perform physico-chemical characterization and in vitro/in vivo studies of unsaturated fatty acids vesicles containing ammonium glycyrrhizinate, obtaining a new topical drug delivery system. The chosen active substance is well known as an anti-inflammatory compound, but its antioxidant activity is also noteworthy. In this way, the obtained nanocarriers are totally natural vesicles and they have shown to have suitable physico-chemical features for topical administration. Moreover, the proposed nanocarriers have proven their ability to improve the in vitro percutaneous permeation and antioxidant activity of ammonium glycyrrhizinate on human keratinocytes (NCTC 2544 cells). In vivo studies, carried out on human volunteers, have demonstrated the biocompatibility of unsaturated fatty acid vesicles toward skin tissue, indicating a possible clinical application of unsaturated fatty acid vesicles for the treatment of topical diseases. Full article

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20 pages, 5932 KiB

Open AccessArticle

Disruption of pH Dynamics Suppresses Proliferation and Potentiates Doxorubicin Cytotoxicity in Breast Cancer Cells

by Diana Tavares-Valente, Bárbara Sousa, Fernando Schmitt, Fátima Baltazar and Odília Queirós

Pharmaceutics 2021, 13(2), 242; https://doi.org/10.3390/pharmaceutics13020242 - 9 Feb 2021

Cited by 11 | Viewed by 2987

Abstract

The reverse pH gradient is a major feature associated with cancer cell reprogrammed metabolism. This phenotype is supported by increased activity of pH regulators like ATPases, carbonic anhydrases (CAs), monocarboxylate transporters (MCTs) and sodium–proton exchangers (NHEs) that induce an acidic tumor microenvironment, responsible [...] Read more.

The reverse pH gradient is a major feature associated with cancer cell reprogrammed metabolism. This phenotype is supported by increased activity of pH regulators like ATPases, carbonic anhydrases (CAs), monocarboxylate transporters (MCTs) and sodium–proton exchangers (NHEs) that induce an acidic tumor microenvironment, responsible for the cancer acid-resistant phenotype. In this work, we analyzed the expression of these pH regulators and explored their inhibition in breast cancer cells as a strategy to enhance the sensitivity to chemotherapy. Expression of the different pH regulators was evaluated by immunofluorescence and Western blot in two breast cancer cell lines (MDA-MB-231 and MCF-7) and by immunohistochemistry in human breast cancer tissues. Cell viability, migration and invasion were evaluated upon exposure to the pH regulator inhibitors (PRIs) concanamycin-A, cariporide, acetazolamide and cyano-4-hydroxycinnamate. Additionally, PRIs were combined with doxorubicin to analyze the effect of cell pH dynamic disruption on doxorubicin sensitivity. Both cancer cell lines expressed all pH regulators, except for MCT1 and CAXII, only expressed in MCF-7 cells. There was higher plasma membrane expression of the pH regulators in human breast cancer tissues than in normal breast epithelium. Additionally, pH regulator expression was significantly associated with different molecular subtypes of breast cancer. pH regulator inhibition decreased cancer cell aggressiveness, with a higher effect in MDA-MB-231. A synergistic inhibitory effect was observed when PRIs were combined with doxorubicin in the breast cancer cell line viability. Our results support proton dynamic disruption as a breast cancer antitumor strategy and the use of PRIs to boost the activity of conventional therapy. Full article

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15 pages, 5463 KiB

Open AccessArticle

The Effect of Myristica fragrans on Texture Properties and Shelf-Life of Innovative Chewable Gel Tablets

by Inga Matulyte, Akvile Mataraite, Saule Velziene and Jurga Bernatoniene

Pharmaceutics 2021, 13(2), 238; https://doi.org/10.3390/pharmaceutics13020238 - 9 Feb 2021

Cited by 11 | Viewed by 4165

Abstract

Chewable gel tablets are an underdeveloped subject, even though there are many simple chewable tablets and gummy candies in the food and pharmaceutical industries. Chewable gel tablets are not as sweet, they can have an active substance, pharmacological effect, and a value of [...] Read more.

Chewable gel tablets are an underdeveloped subject, even though there are many simple chewable tablets and gummy candies in the food and pharmaceutical industries. Chewable gel tablets are not as sweet, they can have an active substance, pharmacological effect, and a value of nutrition. The aim of this study was to prepare gelatin-based chewable tablets with Myristica fragrans as a preservative and to determine the shelf-life variability depending on storage conditions, and to evaluate texture changes. Firmness and springiness of gel tablets were measured by a texture analyzer and compared between different storage conditions and the shelf-life of tablets was established by mold growing time. Chewable gel tablets were prepared by using silicone form. Mold was most likely to grow on tablets that have been packaged in squeezable bags (after 14 days 60% of all formulations had a mold, p < 0.05). The most stable tablets (over 180 days) were in sealed boxes and contained nutmeg essential oil or its solution, or ethanolic nutmeg extract. The gel tablets’ firmness increased about 4 times when they were stored in opened plastic boxes and their springiness decreased about 1.65 times after 28 days in the mentioned conditions, p < 0.05. Nutmeg hydrolat had the highest influence on texture variation (p < 0.05). Full article

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21 pages, 3535 KiB

Open AccessArticle

Nanoemulsions of Satureja montana Essential Oil: Antimicrobial and Antibiofilm Activity against Avian Escherichia coli Strains

by Federica Rinaldi, Linda Maurizi, Antonietta Lucia Conte, Massimiliano Marazzato, Alessandro Maccelli, Maria Elisa Crestoni, Patrizia Nadia Hanieh, Jacopo Forte, Maria Pia Conte, Carlo Zagaglia, Catia Longhi, Carlotta Marianecci, Maria Grazia Ammendolia and Maria Carafa

Pharmaceutics 2021, 13(2), 134; https://doi.org/10.3390/pharmaceutics13020134 - 21 Jan 2021

Cited by 15 | Viewed by 3523

Abstract

Satureja montana essential oil (SEO) presents a wide range of biological activities due to its high content of active phytochemicals. In order to improve the essential oil’s (EO) properties, oil in water nanoemulsions (NEs) composed of SEO and Tween-80 were prepared, characterized, and [...] Read more.

Satureja montana essential oil (SEO) presents a wide range of biological activities due to its high content of active phytochemicals. In order to improve the essential oil’s (EO) properties, oil in water nanoemulsions (NEs) composed of SEO and Tween-80 were prepared, characterized, and their antimicrobial and antibiofilm properties assayed against Escherichia coli strains isolated from healthy chicken. Since surfactant and oil composition can strongly influence NE features and their application field, a ternary phase diagram was constructed and evaluated to select a suitable surfactant/oil/water ratio. Minimal inhibitory concentration and minimal bactericidal concentration of NEs, evaluated by the microdilution method, showed that the SEO NE formulation exhibited higher inhibitory effects against planktonic E. coli than SEO alone. The quantification of biofilm production in the presence of NEs, assessed by crystal violet staining and scanning electron microscopy, evidenced that sub-MIC concentrations of SEO NEs enable an efficient reduction of biofilm production by the strong producer strains. The optimized nanoemulsion formulation could ensure food safety quality, and counteract the antibiotic resistance of poultry associated E. coli, if applied/aerosolized in poultry farms. Full article

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2020

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17 pages, 2394 KiB

Open AccessArticle

Effect of Plant Extracts on the Characteristics of Silver Nanoparticles for Topical Application

by Ioanna K. Siakavella, Fotini Lamari, Dimitrios Papoulis, Malvina Orkoula, Patroula Gkolfi, Michail Lykouras, Konstantinos Avgoustakis and Sophia Hatziantoniou

Pharmaceutics 2020, 12(12), 1244; https://doi.org/10.3390/pharmaceutics12121244 - 21 Dec 2020

Cited by 52 | Viewed by 4351

Abstract

Silver nanoparticles (AgNPs) were synthesized using hydroalcoholic extracts of dittany (Origanum dictamnus), sage (Salvia officinalis), sea buckthorn (Elaeagnus rhamnoides, syn. Hippophae rhamnoides), and calendula (Calendula officinalis) as reducing agents. AgNPs synthesized using NaBH₄ [...] Read more.

Silver nanoparticles (AgNPs) were synthesized using hydroalcoholic extracts of dittany (Origanum dictamnus), sage (Salvia officinalis), sea buckthorn (Elaeagnus rhamnoides, syn. Hippophae rhamnoides), and calendula (Calendula officinalis) as reducing agents. AgNPs synthesized using NaBH₄ and citric acid were used as control. The impact of the origin of the extract and preparation conditions (light, temperature, reaction time) on the properties of the synthesized AgNPs was investigated. The structure, morphology, composition, physicochemical characteristics, and colloidal stability were characterized using dynamic laser scattering (DLS), ultraviolet-visible spectrophotometry (UV–/Vis), XRD, X-ray fluorescence (XRF), TEM, and FTΙR. The reduction of total phenolic and flavonoid content of the extracts after the reaction of AgNPs synthesis was also determined. Low IC50 values for all types of AgNPs revealed good antioxidant activity, attributable to the phenolic and flavonoid content of their surface. The results suggest that plant extract selection is important to the green synthesis of AgNPs because it affects the kinetics of their synthesis as well as their morphology, physicochemical characteristics, and colloidal stability. In vitro permeation studies on porcine skin revealed that AgNPs remained at the upper layers of stratum corneum and did not penetrate the skin barrier after 4 h of cutaneous application suggesting the safety of their application on intact skin for a relatively short time. Full article

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20 pages, 2689 KiB

Open AccessArticle

Design and Characterization of Glyceryl Monooleate-Nanostructures Containing Doxorubicin Hydrochloride

by Agnese Gagliardi, Donato Cosco, Betty P. Udongo, Luciana Dini, Giuseppe Viglietto and Donatella Paolino

Pharmaceutics 2020, 12(11), 1017; https://doi.org/10.3390/pharmaceutics12111017 - 24 Oct 2020

Cited by 36 | Viewed by 3709

Abstract

Glyceryl monooleate (GMO) is one of the most popular amphiphilic lipids, which, in the presence of different amounts of water and a proper amount of stabilizer, can promote the development of well defined, thermodynamically stable nanostructures, called lyotropic liquid crystal dispersions. The aim [...] Read more.

Glyceryl monooleate (GMO) is one of the most popular amphiphilic lipids, which, in the presence of different amounts of water and a proper amount of stabilizer, can promote the development of well defined, thermodynamically stable nanostructures, called lyotropic liquid crystal dispersions. The aim of this study is based on the design, characterization, and evaluation of the cytotoxicity of lyotropic liquid crystal nanostructures containing a model anticancer drug such as doxorubicin hydrochloride. The drug is efficiently retained by the GMO nanosystems by a remote loading approach. The nanostructures prepared with different non-ionic surfactants (poloxamers and polysorbates) are characterized by different physico-chemical features as a function of several parameters, i.e., serum stability, temperature, and different pH values, as well as the amount of cryoprotectants used to obtain suitable freeze-dried systems. The nanostructures prepared with poloxamer 407 used as a stabilizer show an increased toxicity of the entrapped drug on breast cancer cell lines (MCF-7 and MDA-MB-231) due to their ability to sensitize multidrug-resistant (MDR) tumor cells through the inhibition of specific drug efflux transporters. Moreover, the interaction between the nanostructures and the cells occurs after just a few hours, evidencing a huge cellular uptake of the nanosystems. Full article

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