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Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Nanochemistry".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 26400

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Prof. Dr. Rita Cortesi

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Department of Chemical, Pharmaceutical and Agricultural Sciences (DoCPAS), University of Ferrara, 44121 Ferrara, Italy
Interests: nanomedicine; liposomes and lipid-based nanosystems; vesicles; microparticles; biomaterials; drug delivery
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Dear Colleagues，

Modern nanotechnology is a multidisciplinary area that has recently stimulated interest in nanoscale products. Indeed, nanotechnology profoundly impacts our lives in both positive and negative ways. Many studies have demonstrated that lipid-based nanoparticles (e.g. nanostructured lipid carriers, solid lipid nanoparticles, nanoemulsions, liposomes and cubosomes) represent a versatile system with applications in many fields, including the environmental, veterinary, nutraceutical, cosmetic, biotechnological, biomedical and pharmaceutical industries. Lipid-based nanosystems are largely used to ameliorate active principle solubility or obtain a controlled or target release, creating a modifiable system able to be adapted according to the product requirements. Indeed, lipid-based nanoparticles are able to solubilize a number of molecules with different physicochemical properties in a biocompatible and biodegradable matrix with well-established safety profiles. Moreover, as a natural resource, lipid nanoparticles also significantly contribute to green nanosystems.

Taking into accounts the various approaches to nanotechnology presented in the previous Special Issues, “Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields I and II”, the third installment in this series will provide an open forum with which to elaborate upon these themes. The primary aim of this issue remains to encourage the exchange of research and findings in the field of nanotechnology. Submissions may be in the form of original research or review articles and may focus on a range of issues, such as the production, characterization, structure and innovative aspects of lipid nanoparticles, possibly presenting new preparation methods, advantages, disadvantages, lipid nanoparticles functionalization and new applications. Studies with multidisciplinary inputs offering innovative methodologies or insights are also welcome.

Prof. Dr. Rita Cortesi
Guest Editor

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Keywords

nanocarriers
nanotechnology
SLN
NLC
liposomes
drug delivery
nanomedicine
green agriculture

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Related Special Issue

Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields IV in Molecules (3 articles)

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Research

16 pages, 2678 KiB

Open AccessArticle

Development of Solid Lipid Nanoparticles as Dry Powder: Characterization and Formulation Considerations

by Debora Santonocito, Maria Grazia Sarpietro, Francesco Castelli, Maria Rosaria Lauro, Cristina Torrisi, Stefano Russo and Carmelo Puglia

Molecules 2023, 28(4), 1545; https://doi.org/10.3390/molecules28041545 - 5 Feb 2023

Cited by 5 | Viewed by 3347

Abstract

Solid lipid nanoparticles (SLNs) are lipid-based colloidal systems used for the delivery of active compounds. Although SLNs have many benefits, they show important issues due to physical and chemical instability phenomena during storage. For these reasons, it is highly desirable to have a dried SLN formulation available. Therefore, the aim of the project was to identify suitable methods to obtain a dry powder formulation from an SLN suspension. The nanoparticle suspension was dried using both freeze- and spray-drying techniques. The suitability of these methods in obtaining SLN dry powders was evaluated from the analyses of nanotechnological parameters, system morphology and thermal behavior using differential scanning calorimetry. Results pointed out that both drying techniques, although at different yields, were able to produce an SLN dry powder suitable for pharmaceutical applications. Noteworthily, the freeze-drying of SLNs under optimized conditions led to a dry powder endowed with good reconstitution properties and technological parameters similar to the starting conditions. Moreover, freeze–thaw cycles were carried out as a pretest to study the protective effect of different cryoprotectants (e.g., glucose and mannitol with a concentration ranging from 1% to 10% w/v). Glucose proved to be the most effective in preventing particle growth during freezing, thawing, and freeze-drying processes; in particular, the optimum concentration of glucose was 1% w/v. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III)

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13 pages, 8862 KiB

Open AccessFeature PaperArticle

Acute Toxicity Evaluation of Phosphatidylcholine Nanoliposomes Containing Nisin in Caenorhabditis elegans

by Juliana Ferreira Boelter, Solange Cristina Garcia, Gabriela Göethel, Mariele Feiffer Charão, Livia Marchi de Melo and Adriano Brandelli

Molecules 2023, 28(2), 563; https://doi.org/10.3390/molecules28020563 - 5 Jan 2023

Cited by 5 | Viewed by 2238

Abstract

Liposomes are among the most studied nanostructures. They are effective carriers of active substances both in the clinical field, such as delivering genes and drugs, and in the food industry, such as promoting the controlled release of bioactive substances, including food preservatives. However, toxicological screenings must be performed to ensure the safety of nanoformulations. In this study, the nematode Caenorhabditis elegans was used as an alternative model to investigate the potential in vivo toxicity of nanoliposomes encapsulating the antimicrobial peptide nisin. The effects of liposomes containing nisin, control liposomes, and free nisin were evaluated through the survival rate, lethal dose (LD₅₀), nematode development rate, and oxidative stress status by performing mutant strain, TBARS, and ROS analyses. Due to its low toxicity, it was not possible to experimentally determine the LD₅₀ of liposomes. The survival rates of control liposomes and nisin-loaded liposomes were 94.3 and 73.6%, respectively. The LD₅₀ of free nisin was calculated as 0.239 mg mL⁻¹. Free nisin at a concentration of 0.2 mg mL⁻¹ significantly affected the development of C. elegans, which was 25% smaller than the control and liposome-treated samples. A significant increase in ROS levels was observed after exposure to the highest concentrations of liposomes and free nisin, coinciding with a significant increase in catalase levels. The treatments induced lipid peroxidation as evaluated by TBARS assay. Liposome encapsulation reduces the deleterious effect on C. elegans and can be considered a nontoxic delivery system for nisin. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III)

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20 pages, 4213 KiB

Open AccessArticle

Optimization of Gefitinib-Loaded Nanostructured Lipid Carrier as a Biomedical Tool in the Treatment of Metastatic Lung Cancer

by Abdelrahman Y. Sherif, Gamaleldin I. Harisa, Ahmad A. Shahba, Fars K. Alanazi and Wajhul Qamar

Molecules 2023, 28(1), 448; https://doi.org/10.3390/molecules28010448 - 3 Jan 2023

Cited by 14 | Viewed by 2784

Abstract

Gefitinib (GEF) is utilized in clinical settings for the treatment of metastatic lung cancer. However, premature drug release from nanoparticles in vivo increases the exposure of systemic organs to GEF. Herein, nanostructured lipid carriers (NLC) were utilized not only to avoid premature drug release but also due to their inherent lymphatic tropism. Therefore, the present study aimed to develop a GEF-NLC as a lymphatic drug delivery system with low drug release. Design of experiments was utilized to develop a stable GEF-NLC as a lymphatic drug delivery system for the treatment of metastatic lung cancer. The in vitro drug release of GEF from the prepared GEF-NLC formulations was studied to select the optimum formulation. MTT assay was utilized to study the cytotoxic activity of GEF-NLC compared to free GEF. The optimized GEF-NLC formulation showed favorable physicochemical properties: <300 nm PS, <0.2 PDI, <−20 ZP values with >90% entrapment efficiency. Interestingly, the prepared formulation was able to retain GEF with only ≈57% drug release within 24 h. Furthermore, GEF-NLC reduced the sudden exposure of cultured cells to GEF and produced the required cytotoxic effect after 48 and 72 h incubation time. Consequently, optimized formulation offers a promising approach to improve GEF’s therapeutic outcomes with reduced systemic toxicity in treating metastatic lung cancer. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III)

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22 pages, 2627 KiB

Open AccessArticle

Nanostructured Lipid Carriers (NLC)-Based Gel Formulations as Etodolac Delivery: From Gel Preparation to Permeation Study

by Anna Czajkowska-Kośnik, Emilia Szymańska and Katarzyna Winnicka

Molecules 2023, 28(1), 235; https://doi.org/10.3390/molecules28010235 - 28 Dec 2022

Cited by 10 | Viewed by 3306

Abstract

Topical administration of drug is an attractive alternative to the oral administration as it provides a reduction in adverse reactions and an enhancement of therapeutic effects. The use of lipid carriers in hydrogel structures makes it possible to introduce lipophilic substances in a dissolved form. In this study, an NSAID from the BCS class II, etodolac (ETD), was used. The nanostructured lipid carriers (NLC) obtained with ETD were incorporated into semi-solid forms (gels). Hydrogels with the suspended drug and oleogel were also prepared for comparison purposes. The obtained gels were tested in terms of pH, viscosity, rheological, mechanical, and bioadhesive properties. The release and permeation through membranes were also studied. All tested formulations were characterized by a pH below 7, which ensured the physiological state of the skin. The viscosities of all gels decreased with increasing shear rate, indicating non-Newtonian behavior. The fastest ETD release was observed for NLC with a Carbopol base (formulation F1); a similar result was noticed in the permeation test. The developed gel formulations containing ETD-NLC dispersion and Carbopol or Poloxamer as gelling agents were stable and possessed beneficial pharmaceutical properties. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III)

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18 pages, 3000 KiB

Open AccessArticle

Compritol-Based Alprazolam Solid Lipid Nanoparticles for Sustained Release of Alprazolam: Preparation by Hot Melt Encapsulation

by Huma Rao, Saeed Ahmad, Asadullah Madni, Iqra Rao, Mohammed Ghazwani, Umme Hani, Muhammad Umair, Imtiaz Ahmad, Nadia Rai, Maqsood Ahmed and Kashif ur Rehman Khan

Molecules 2022, 27(24), 8894; https://doi.org/10.3390/molecules27248894 - 14 Dec 2022

Cited by 8 | Viewed by 2435

Abstract

The current study was designed to investigate the feasibility of incorporating the water-insoluble lipophilic drug Alprazolam (Alp) into solid lipid nanoparticles (SLNs) to offer the combined benefits of the quick onset of action along with the sustained release of the drug. Therefore, compritol-based alprazolam-loaded SLNs (Alp-SLNs) would provide early relief from anxiety and sleep disturbances and long-lasting control of symptoms in patients with depression, thereby enhancing patient compliance. The optimized Alp-SLNs analyzed by DLS and SEM showed consistent particle size of 92.9 nm with PI values and standard deviation of the measurements calculated at <0.3 and negative surface charge. These characteristic values demonstrate the desired level of homogeneity and good physical stability of Alp-SLNs. The SLNs had a good entrapment efficiency (89.4%) and high drug-loading capacity (77.9%). SEM analysis revealed the smooth spherical morphology of the SLNs. The physical condition of alprazolam and absence of interaction among formulation components in Alp-SLNs was confirmed by FTIR and DSC analyses. XRD analysis demonstrated the molecular dispersion of crystalline alprazolam in Alp-SLNs. The in vitro release study implied that the release of Alp from the optimized Alp-SLN formulation was sustained as compared to the Alp drug solution because Alp-SLNs exhibited sustained release of alprazolam over 24 h. Alp-SLNs are a promising candidate to achieve sustained release of the short-acting drug Alp, thereby reducing its dosing frequency and enhancing patient compliance. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III)

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18 pages, 4504 KiB

Open AccessArticle

Docetaxel Loaded in Copaiba Oil-Nanostructured Lipid Carriers as a Promising DDS for Breast Cancer Treatment

by Fabiola Vieira de Carvalho, Ligia Nunes de Morais Ribeiro, Ludmilla David de Moura, Gustavo Henrique Rodrigues da Silva, Hery Mitsutake, Talita Cesarim Mendonça, Gabriela Geronimo, Marcia Cristina Breitkreitz and Eneida de Paula

Molecules 2022, 27(24), 8838; https://doi.org/10.3390/molecules27248838 - 13 Dec 2022

Cited by 10 | Viewed by 2406

Abstract

Breast cancer is the neoplasia of highest incidence in women worldwide. Docetaxel (DTX), a taxoid used to treat breast cancer, is a BCS-class-IV compound (low oral bioavailability, solubility and intestinal permeability). Nanotechnological strategies can improve chemotherapy effectiveness by promoting sustained release and reducing systemic toxicity. Nanostructured lipid carriers (NLC) encapsulate hydrophobic drugs in their blend-of-lipids matrix, and imperfections prevent drug expulsion during storage. This work describes the preparation, by design of experiments (2³ factorial design) of a novel NLC formulation containing copaiba oil (CO) as a functional excipient. The optimized formulation (NLC_DTX) showed approximately 100% DTX encapsulation efficiency and was characterized by different techniques (DLS, NTA, TEM/FE-SEM, DSC and XRD) and was stable for 12 months of storage, at 25 °C. Incorporation into the NLC prolonged drug release for 54 h, compared to commercial DTX (10 h). In vitro cytotoxicity tests revealed the antiproliferative effect of CO and NLC_DTX, by reducing the cell viability of breast cancer (4T1/MCF-7) and healthy (NIH-3T3) cells more than commercial DTX. NLC_DTX thus emerges as a promising drug delivery system of remarkable anticancer effect, (strengthened by CO) and sustained release that, in clinics, may decrease systemic toxicity at lower DTX doses. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III)

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24 pages, 5632 KiB

Open AccessArticle

Design of Quercetin-Loaded Natural Oil-Based Nanostructured Lipid Carriers for the Treatment of Bacterial Skin Infections

by Dragana P. C. de Barros, Rafaela Santos, Patricia Reed, Luís P. Fonseca and Abel Oliva

Molecules 2022, 27(24), 8818; https://doi.org/10.3390/molecules27248818 - 12 Dec 2022

Cited by 13 | Viewed by 2771

Abstract

The biological activity of natural plant-oil-based nanostructured lipid carriers (NPO-NLCs) can be enhanced by the encapsulation of bioactive compounds, and they in turn can improve topical delivery of the drugs. Quercetin (QR), a vital plant flavonoid, expresses antibacterial properties, and we recently showed that empty NPO-NLCs also have antimicrobial activity. The main objective of this study was to evaluate the synergetic effect of loading natural plant-oil-based nanostructured lipid carriers with quercetin (QR-NPO-NLCs) as a topical delivery system for the treatment of bacterial skin infections. Five nanostructured lipid carrier systems containing different oils (sunflower, olive, corn, coconut, and castor) were engineered. The particles’ stability, structural properties, bioavailability, and antimicrobial activity were studied. NLCs with an average size of <200 nm and Z-potential of −40 mV were developed. Stable QR-NPO-NLCs were obtained with high encapsulation efficiency (>99%). The encapsulation of QR decreased cytotoxicity and increased the antioxidant effect of nanocarriers. An increase in antibacterial activity of the systems containing QR was demonstrated against Staphylococcus aureus. QR-NPO-NLCs could transport QR to an intranuclear location within HaCaT cells, indicating that QR-NPO-NLCs are promising candidates for controlled topical drug delivery. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III)

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16 pages, 4335 KiB

Open AccessArticle

Local Delivery of Azithromycin Nanoformulation Attenuated Acute Lung Injury in Mice

by Mohsen G. Alrashedi, Ahmed Shaker Ali, Osama Abdelhakim Ahmed and Ibrahim M. Ibrahim

Molecules 2022, 27(23), 8293; https://doi.org/10.3390/molecules27238293 - 28 Nov 2022

Cited by 4 | Viewed by 2562

Abstract

Humanity has suffered from the coronavirus disease 2019 (COVID-19) pandemic over the past two years, which has left behind millions of deaths. Azithromycin (AZ), an antibiotic used for the treatment of several bacterial infections, has shown antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as against the dengue, Zika, Ebola, and influenza viruses. Additionally, AZ has shown beneficial effects in non-infective diseases such as cystic fibrosis and bronchiectasis. However, the systemic use of AZ in several diseases showed low efficacy and potential cardiac toxicity. The application of nanotechnology to formulate a lung delivery system of AZ could prove to be one of the solutions to overcome these drawbacks. Therefore, we aimed to evaluate the attenuation of acute lung injury in mice via the local delivery of an AZ nanoformulation. The hot emulsification–ultrasonication method was used to prepare nanostructured lipid carrier of AZ (AZ-NLC) pulmonary delivery systems. The developed formulation was evaluated and characterized in vitro and in vivo. The efficacy of the prepared formulation was tested in the bleomycin (BLM) -mice model for acute lung injury. AZ-NLC was given by the intratracheal (IT) route for 6 days at a dose of about one-eighth oral dose of AZ suspension. Samples of lung tissues were taken at the end of the experiment for immunological and histological assessments. AZ-NLC showed an average particle size of 453 nm, polydispersity index of 0.228 ± 0.07, zeta potential of −30 ± 0.21 mV, and a sustained release pattern after the initial 50% drug release within the first 2 h. BLM successfully induced a marked increase in pro-inflammatory markers and also induced histological changes in pulmonary tissues. All these alterations were significantly reversed by the concomitant administration of AZ-NLC (IT). Pulmonary delivery of AZ-NLC offered delivery of the drug locally to lung tissues. Its attenuation of lung tissue inflammation and histological injury induced by bleomycin was likely through the downregulation of the p53 gene and the modulation of Bcl-2 expression. This novel strategy could eventually improve the effectiveness and diminish the adverse drug reactions of AZ. Lung delivery could be a promising treatment for acute lung injury regardless of its cause. However, further work is needed to explore the stability of the formulation, its pharmacokinetics, and its safety. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III)

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14 pages, 4322 KiB

Open AccessArticle

Benzo[k,l]xanthene Lignan-Loaded Solid Lipid Nanoparticles for Topical Application: A Preliminary Study

by Cristina Torrisi, Nunzio Cardullo, Stefano Russo, Alfonsina La Mantia, Rosaria Acquaviva, Vera Muccilli, Francesco Castelli and Maria Grazia Sarpietro

Molecules 2022, 27(18), 5887; https://doi.org/10.3390/molecules27185887 - 10 Sep 2022

Cited by 7 | Viewed by 1854

Abstract

Skin is the first human barrier that is daily exposed to a broad spectrum of physical and chemical agents, which can increase reactive oxygen species (ROS) and lead to the formation of topical disorders. Antioxidant molecules, such as benzo[k,l]xanthene lignans (BXL), are ideal candidates to eliminate or minimize the effects of ROS. Herein, we aimed to formulate BXL-loaded solid lipid nanoparticles (SLN-BXL) to improve the bioavailability and interaction with the skin, and also to investigate the protective impact against intracellular ROS generation in HFF-1 in comparison with the drug-free situation. SLN-BXL were formulated using the PIT/ultrasonication method, and then were subjected to physicochemical characterizations, i.e., average size, zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency (%EE), thermotropic behavior, and interaction with a biomembrane model. The results show a mean size around 200 nm, PDI of 0.2, and zeta potential of about −28 mV, with values almost unchanged over a period of three months, while the EE% is ≈70%. Moreover, SLN-BXL are able to deeply interact with the biomembrane model, and to achieve a double-action release in mildly hydrophobic matrices; the results of the in vitro experiments confirm that SLN-BXL are cell-safe and capable of attenuating the IL-2-induced high ROS levels. In conclusion, based on our findings, the formulation can be proposed as a candidate for a preventive remedy against skin disorders induced by increased levels of ROS. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III)

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15 pages, 12260 KiB

Open AccessArticle

Effect of Ester Moiety on Structural Properties of Binary Mixed Monolayers of Alpha-Tocopherol Derivatives with DPPC

by Grażyna Neunert, Robert Hertmanowski, Stanislaw Witkowski and Krzysztof Polewski

Molecules 2022, 27(15), 4670; https://doi.org/10.3390/molecules27154670 - 22 Jul 2022

Cited by 3 | Viewed by 1521

Abstract

Phospholipid membranes are ubiquitous components of cells involved in physiological processes; thus, knowledge regarding their interactions with other molecules, including tocopherol ester derivatives, is of great importance. The surface pressure–area isotherms of pure α-tocopherol (Toc) and its derivatives (oxalate (OT), malonate (MT), succinate (ST), and carbo analog (CT)) were studied in Langmuir monolayers in order to evaluate phase formation, compressibility, packing, and ordering. The isotherms and compressibility results indicate that, under pressure, the ester derivatives and CT are able to form two-dimensional liquid-condensed (LC) ordered structures with collapse pressures ranging from 27 mN/m for CT to 44 mN/m for OT. Next, the effect of length of ester moiety on the surface behavior of DPPC/Toc derivatives’ binary monolayers at air–water interface was investigated. The average molecular area, elastic modulus, compressibility, and miscibility were calculated as a function of molar fraction of derivatives. Increasing the presence of Toc derivatives in DPPC monolayer induces expansion of isotherms, increased monolayer elasticity, interrupted packing, and lowered ordering in monolayer, leading to its fluidization. Decreasing collapse pressure with increasing molar ratio of derivatives indicates on the miscibility of Toc esters in DPPC monolayer. The interactions between components were analyzed using additivity rule and thermodynamic calculations of excess and total Gibbs energy of mixing. Calculated excess area and Gibbs energy indicated repulsion between components, confirming their partial mixing. In summary, the mechanism of the observed phenomena is mainly connected with interactions of ionized carboxyl groups of ester moieties with DPPC headgroup moieties where formed conformations perturb alignment of acyl chains, resulting in increasing mean area per molecule, leading to disordering and fluidization of mixed monolayer. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields III)

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