Pharmaceutics

Research

14 pages, 1143 KiB

Open AccessArticle

Development of Sedative Dexmedetomidine Sublingual In Situ Gels: In Vitro and In Vivo Evaluations

by Ayat A. Allam, Nermin E. Eleraky, Nadeen H. Diab, Mahmoud Elsabahy, Sahar A. Mohamed, Hala S. Abdel-Ghaffar, Nivin A. Hassan, Samia A. Shouman, Mervat M. Omran, Sahar B. Hassan and Noura G. Eissa

Pharmaceutics 2022, 14(2), 220; https://doi.org/10.3390/pharmaceutics14020220 - 18 Jan 2022

Cited by 5 | Viewed by 3014

Abstract

Intravenous dexmedetomidine (DEX) is currently approved by the FDA for the sedation of intubated patients in intensive care units to reduce anxiety and to augment postoperative analgesia. Bradycardia and hypotension are limitations associated with the intravenous administration of DEX. In this study, DEX [...] Read more.

Intravenous dexmedetomidine (DEX) is currently approved by the FDA for the sedation of intubated patients in intensive care units to reduce anxiety and to augment postoperative analgesia. Bradycardia and hypotension are limitations associated with the intravenous administration of DEX. In this study, DEX sublingual in situ gels were developed and assessed for their pH, gelling capacity, viscosity, mucoadhesion and in vitro drug release. The optimized gelling system demonstrated enhanced mucoadhesion, superior gelling capacity, reasonable pH and optimal rheological profile. In vivo, compared to the oral solution, the optimal sublingual gel resulted in a significant higher rate and extent of bioavailability. Although the in situ gel had comparable plasma levels to those observed following intravenous administration, significant amelioration of the systemic adverse reactions were attained. As demonstrated by the hot plate method, a sustained duration of analgesia in rats was observed after sublingual administration of DEX gel compared to the intravenously administered DEX solution. Furthermore, no changes in systolic blood pressure and heart rate were recorded in rats and rabbits, respectively, after sublingual administration of DEX. Sublingual administration of DEX in situ gel provides a promising approach for analgesia and sedation, while circumventing the reported adverse reactions associated with intravenous administration of DEX. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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12 pages, 3763 KiB

Open AccessArticle

The Fast Track for Intestinal Tumor Cell Differentiation and In Vitro Intestinal Models by Inorganic Topographic Surfaces

by Matteo Centonze, Erwin J. W. Berenschot, Simona Serrati, Arturo Susarrey-Arce and Silke Krol

Pharmaceutics 2022, 14(1), 218; https://doi.org/10.3390/pharmaceutics14010218 - 17 Jan 2022

Cited by 2 | Viewed by 3794

Abstract

Three-dimensional (3D) complex in vitro cell systems are well suited to providing meaningful and translatable results in drug screening, toxicity measurements, and biological studies. Reliable complex gastrointestinal in vitro models as a testbed for oral drug administration and toxicity are very valuable in [...] Read more.

Three-dimensional (3D) complex in vitro cell systems are well suited to providing meaningful and translatable results in drug screening, toxicity measurements, and biological studies. Reliable complex gastrointestinal in vitro models as a testbed for oral drug administration and toxicity are very valuable in achieving predictive results for clinical trials and reducing animal testing. However, producing these models is time-consuming due to the lengthy differentiation of HT29 or other cells into mucus-producing goblet cells or other intestinal cell lineages. In the present work, HT29 cells were grown on an inorganic topographic surface decorated with a periodic pattern of micrometre-sized amorphous SiO₂ structures for up to 35 days. HT29 cells on topographic surfaces were compared to undifferentiated HT29 in glucose-containing medium on glass or culture dish and with HT29 cells differentiated for 30 days in the presence of methotrexate (HT29-MTX). The cells were stained with Alcian blue for mucus, antibodies for mucus 2 (goblet cells), villin (enterocytes), lysozyme (Paneth cells), and FITC-labeled lectins to identify different cells, glycomic profiles, and cell features. We observed that HT29 cells on topographic surfaces showed more similarities with the differentiated HT29-MTX than with undifferentiated HT29. They formed islands of cell clusters, as observed for HT29-MTX. Already after 2 days, the first mucus secretion was shown by Alcian blue stain and FITC-wheat germ agglutinin. After 4–6 days, mucus was observed on the cell surface and in the intercellular space. The cell layer was undulated, and in 3D reconstruction, the cells showed a clear polarisation with a strong actin signal to one membrane. The lectins and the antibody-staining confirmed the heterogeneous composition of differentiated HT29 cells on topographic surfaces after 6–8 days, or after 6–8 days following MTX differentiation (30 days). Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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13 pages, 2208 KiB

Open AccessArticle

Synergy of Hydeal-D^® and Hyaluronic Acid for Protecting and Restoring Urothelium: In Vitro Characterization

by Marco Ruggeri, Mauro Pavan, Matteo Soato, Susi Panfilo, Carlo Barbera, Devis Galesso, Dalila Miele, Silvia Rossi, Alba Di Lucia, Franca Ferrari and Giuseppina Sandri

Pharmaceutics 2021, 13(9), 1450; https://doi.org/10.3390/pharmaceutics13091450 - 11 Sep 2021

Cited by 3 | Viewed by 2893

Abstract

Interstitial cystitis (IC) or painful bladder syndrome is a chronic dysfunction due to an inflammatory condition, characterized by bladder pain and urinary frequency. Currently, no gold standard therapy is available since IC does not respond to conventional ones. Given these premises, the aim [...] Read more.

Interstitial cystitis (IC) or painful bladder syndrome is a chronic dysfunction due to an inflammatory condition, characterized by bladder pain and urinary frequency. Currently, no gold standard therapy is available since IC does not respond to conventional ones. Given these premises, the aim of this work was the in vitro characterization of biological properties (mucoadhesion and anti-inflammatory activity) of a commercial product (HydealCyst–HydC) based on hyaluronic acid (HA) and the benzyl ester of HA (Hydeal-D^®) intended for bladder instillation to restore and/or protect the urothelial layer of glycosamino glycans (GAGs). The in vitro characterization demonstrated that an interaction product is formed between HA and Hydeal-D^® that has a role in the rheological behavior and mucoadhesive properties. HA was identified as a key component to form the mucoadhesive joint, while the interaction of HA with Hydeal-D^® improved polysaccharide stability and prolonged the activity ex vivo. Moreover, HydC is cytocompatible with urothelial cells (HTB-4) and possesses an anti-inflammatory effect towards these cells by decreasing the secretion of IL-6 and IL-8, which were both increased in patients with IC, and by increasing the secretion of sulfated GAGs. These two findings, along with the resilience properties of the formulation due to mucoadhesion, suggest the active role of HydC in protecting and restoring urothelium homeostasis. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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16 pages, 5341 KiB

Open AccessArticle

Transmucosal Solid Lipid Nanoparticles to Improve Genistein Absorption via Intestinal Lymphatic Transport

by Antonella Obinu, Giovanni Pietro Burrai, Roberta Cavalli, Grazia Galleri, Rossana Migheli, Elisabetta Antuofermo, Giovanna Rassu, Elisabetta Gavini and Paolo Giunchedi

Pharmaceutics 2021, 13(2), 267; https://doi.org/10.3390/pharmaceutics13020267 - 16 Feb 2021

Cited by 26 | Viewed by 3120

Abstract

Genistein (GEN) is a soy-derived isoflavone that exhibits several biological effects, such as neuroprotective activity and the prevention of several types of cancer and cardiovascular disease. However, due to its poor water solubility and the extensive first-pass metabolism, the oral bioavailability of GEN [...] Read more.

Genistein (GEN) is a soy-derived isoflavone that exhibits several biological effects, such as neuroprotective activity and the prevention of several types of cancer and cardiovascular disease. However, due to its poor water solubility and the extensive first-pass metabolism, the oral bioavailability of GEN is limited. In this work, solid lipid nanoparticles (SLN) were developed to preferentially reach the intestinal lymphatic vessels, avoiding the first-pass metabolism of GEN. GEN-loaded SLN were obtained by a hot homogenization process, and the formulation parameters were chosen based on already formulated studies. The nanoparticles were characterized, and the preliminary in vitro chylomicron formation was evaluated. The cell uptake of selected nanocarriers was studied on the Caco-2 cell line and intestinal mucosa. The SLN, characterized by a spherical shape, showed an average diameter (about 280 nm) suitable for an intestinal lymphatic uptake, good stability during the testing time, and high drug loading capacity. Furthermore, the intestinal mucosa and Caco-2 cells were found to uptake SLN. The approximately two-fold increase in particle size suggested a possible interaction between SLN and the lipid components of chylomicrons like phospholipid; therefore, the results may support the potential for these SLN to improve oral GEN bioavailability via intestinal lymphatic absorption. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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17 pages, 2465 KiB

Open AccessArticle

Improved Bioavailability of Montelukast through a Novel Oral Mucoadhesive Film in Humans and Mice

by Johanna Michael, Diana Bessa de Sousa, Justin Conway, Erick Gonzalez-Labrada, Rodolphe Obeid, Julia Tevini, Thomas Felder, Birgit Hutter-Paier, Horst Zerbe, Nadine Paiement and Ludwig Aigner

Pharmaceutics 2021, 13(1), 12; https://doi.org/10.3390/pharmaceutics13010012 - 23 Dec 2020

Cited by 8 | Viewed by 4028

Abstract

The leukotriene receptor antagonist Montelukast (MTK) is an approved medication for the treatment of asthma and allergic rhinitis. The existing marketed tablet forms of MTK exhibit inconsistent uptake and bioavailability, which partially explains the presence of a significant proportion of MTK low- and [...] Read more.

The leukotriene receptor antagonist Montelukast (MTK) is an approved medication for the treatment of asthma and allergic rhinitis. The existing marketed tablet forms of MTK exhibit inconsistent uptake and bioavailability, which partially explains the presence of a significant proportion of MTK low- and non-responders in the population. Besides that, tablets are suboptimal formulations for patients suffering from dysphagia, for example, seen in patients with neurodegenerative diseases such as Alzheimer’s disease, a disease with increasing interest in repurposing of MTK. This, and the need for an improved bioavailability, triggered us to reformulate MTK. Our aim was to develop a mucoadhesive MTK film with good safety and improved pharmacological features, i.e., an improved bioavailability profile in humans as well as in a mouse model of Alzheimer’s disease. We tested dissolution of the MTK mucoadhesive film and assessed pharmacoexposure and kinetics after acute and chronic oral application in mice. Furthermore, we performed a Phase I analysis in humans, which included a comparison with the marketed tablet form as well as a quantitative analysis of the MTK levels in the cerebrospinal fluid. The novel MTK film demonstrated significantly improved bioavailability compared to the marketed tablet in the clinical Phase 1a study. Furthermore, there were measurable amounts of MTK present in the cerebrospinal fluid (CSF). In mice, MTK was detected in serum and CSF after acute and chronic exposure in a dose-dependent manner. The mucoadhesive film of MTK represents a promising alternative for the tablet delivery. The oral film might lower the non-responder rate in patients with asthma and might be an interesting product for repurposing of MTK in other diseases. As we demonstrate Blood-Brain-Barrier (BBB) penetrance in a preclinical model, as well as in a clinical study, the oral film of MTK might find its use as a therapeutic for acute and chronic neurodegenerative diseases such as dementias and stroke. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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23 pages, 5181 KiB

Open AccessArticle

Development and Characterization of Potential Ocular Mucoadhesive Nano Lipid Carriers Using Full Factorial Design

by Eszter L. Kiss, Szilvia Berkó, Attila Gácsi, Anita Kovács, Gábor Katona, Judit Soós, Erzsébet Csányi, Ilona Gróf, András Harazin, Mária A. Deli, György T. Balogh and Mária Budai-Szűcs

Pharmaceutics 2020, 12(7), 682; https://doi.org/10.3390/pharmaceutics12070682 - 20 Jul 2020

Cited by 17 | Viewed by 3649

Abstract

Generally, topically applied eye drops have low bioavailability due to short residence time and low penetration of the drug. The aim of the present study was to incorporate dexamethasone (DXM) into nano lipid carriers (NLC), which contain mucoadhesive polymer, in order to increase [...] Read more.

Generally, topically applied eye drops have low bioavailability due to short residence time and low penetration of the drug. The aim of the present study was to incorporate dexamethasone (DXM) into nano lipid carriers (NLC), which contain mucoadhesive polymer, in order to increase the bioavailability of the drug. A 2³ factorial experimental design was applied, in which the three factors were the polymer, the DXM, and the emulsifier concentrations. The samples were analyzed for particle size, zeta potential, polydispersity index, and Span value. The significant factors were identified. The biocompatibility of the formulations was evaluated with human corneal toxicity tests and immunoassay analysis. The possible increase in bioavailability was analyzed by means of mucoadhesivity, in vitro drug diffusion, and different penetration tests, such as in vitro cornea PAMPA model, human corneal cell penetration, and ex vivo porcine corneal penetration using Raman mapping. The results indicated that DXM can be incorporated in stable mucoadhesive NLC systems, which are non-toxic and do not have any harmful effect on cell junctions. Mucoadhesive NLCs can create a depot on the surface of the cornea, which can predict improved bioavailability. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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24 pages, 4877 KiB

Open AccessArticle

Bilayer Mucoadhesive Buccal Film for Mucosal Ulcers Treatment: Development, Characterization, and Single Study Case

by Thais F. R. Alves, Alesssandra C. Rios, Katiusca da Silva Pontes, Decio L. Portella, Norberto Aranha, Patricia Severino, Eliana B. Souto, Joyce K. M. Gonsalves, Rogeria de Souza Nunes and Marco V. Chaud

Pharmaceutics 2020, 12(7), 657; https://doi.org/10.3390/pharmaceutics12070657 - 11 Jul 2020

Cited by 33 | Viewed by 6635

Abstract

The formation of mucosal ulcers is an end result of epithelial damage, and it occurs due to some specific causes, such as trauma, aphthous stomatitis, lichen planus and lichenoid reactions, cytotoxic effects of chemotherapy and radiation, and drug-induced hypersensitivity reactions and malignant settings. [...] Read more.

The formation of mucosal ulcers is an end result of epithelial damage, and it occurs due to some specific causes, such as trauma, aphthous stomatitis, lichen planus and lichenoid reactions, cytotoxic effects of chemotherapy and radiation, and drug-induced hypersensitivity reactions and malignant settings. This study focused on films for target drug delivery with respect to the treatment of the diseases of the oral mucosa, specifically mucositis. The results of a single clinical study as a pre-experimental design was performed and followed up to the outcome until 30 days. The polymeric film was prepared in a mucoadhesive bilayer structure: the basal layer with lidocaine HCl had a faster release than the apical layer with benzydamine HCl and N-acetyl-cysteine. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and SEM characterized the physical–chemical and morphological properties. The cell viability and cytotoxicity were evaluated in cell line MCF7. The transport mechanism of the solvent (swelling) and the drugs in the basal or apical layer (drug release) was explained with mathematical models. To evaluate the effect of movement inside the mouth, the folding endurance was determined. The mucoadhesive bilayer film is biologically safe and stimulates cellular proliferation. A single study in vivo demonstrated the therapeutic effect of the mucoadhesive bilayer film in buccal mucositis. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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15 pages, 1676 KiB

Open AccessArticle

The Vaginal-PVPA: A Vaginal Mucosa-Mimicking In Vitro Permeation Tool for Evaluation of Mucoadhesive Formulations

by Margherita Falavigna, Martina Pattacini, Richard Wibel, Fabio Sonvico, Natasa Škalko-Basnet and Gøril Eide Flaten

Pharmaceutics 2020, 12(6), 568; https://doi.org/10.3390/pharmaceutics12060568 - 19 Jun 2020

Cited by 15 | Viewed by 4443

Abstract

Drug administration to the vaginal site has gained increasing attention in past decades, highlighting the need for reliable in vitro methods to assess the performance of novel formulations. To optimize formulations destined for the vaginal site, it is important to evaluate the drug [...] Read more.

Drug administration to the vaginal site has gained increasing attention in past decades, highlighting the need for reliable in vitro methods to assess the performance of novel formulations. To optimize formulations destined for the vaginal site, it is important to evaluate the drug retention within the vagina as well as its permeation across the mucosa, particularly in the presence of vaginal fluids. Herewith, the vaginal-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model was validated as a tool to evaluate the permeation of the anti-inflammatory drug ibuprofen from liposomal formulations (i.e., plain and chitosan-coated liposomes). Drug permeation was assessed in the presence and absence of mucus and simulated vaginal fluid (SVF) at pH conditions mimicking both the healthy vaginal premenopausal conditions and vaginal infection/pre-puberty/post-menopause state. The permeation of ibuprofen proved to depend on the type of formulation (i.e., chitosan-coated liposomes exhibited lower drug permeation), the mucoadhesive formulation properties and pH condition. This study highlights both the importance of mucus and SVF in the vaginal model to better understand and predict the in vivo performance of formulations destined for vaginal administration, and the suitability of the vaginal-PVPA model for such investigations. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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19 pages, 2769 KiB

Open AccessArticle

In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics

by Pierre-Louis Destruel, Ni Zeng, Françoise Brignole-Baudouin, Sophie Douat, Johanne Seguin, Elodie Olivier, Melody Dutot, Patrice Rat, Sophie Dufaÿ, Amélie Dufaÿ-Wojcicki, Marc Maury, Nathalie Mignet and Vincent Boudy

Pharmaceutics 2020, 12(4), 360; https://doi.org/10.3390/pharmaceutics12040360 - 15 Apr 2020

Cited by 25 | Viewed by 4445

Abstract

Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Nowadays, phenylephrine hydrochloride (PHE) and tropicamide (TPC) are extensively used to induce mydriasis. Several pharmaceutic dosage forms of these two active ingredients have been described. However, no optimal therapeutic strategy has reached [...] Read more.

Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Nowadays, phenylephrine hydrochloride (PHE) and tropicamide (TPC) are extensively used to induce mydriasis. Several pharmaceutic dosage forms of these two active ingredients have been described. However, no optimal therapeutic strategy has reached the market. The present work focuses on the formulation and evaluation of a mucoadhesive ion-activated in situ gelling delivery system based on gellan gum and hydroxyethylcellulose (HEC) for the delivery of phenylephrine and tropicamide. First, in vitro drug release was studied to assess appropriate sustained drug delivery on the ocular surface region. Drug release mechanisms were explored and explained using mathematical modeling. Then, in situ gelling delivery systems were visualized using scanning electron microscopy illustrating the drug release phenomena involved. Afterward, cytotoxicity of the developed formulations was studied and compared with those of commercially available eye drops. Human epithelial corneal cells were used. Finally, mydriasis intensity and kinetic was investigated in vivo. Mydriasis pharmacodynamics was studied by non-invasive optical imaging on vigilant rabbits, allowing eye blinking and nasolacrimal drainage to occur physiologically. In situ gelling delivery systems mydriasis profiles exhibited a significant increase of intensity and duration compared with those of conventional eye drops. Efficient mydriasis was achieved following the administration of a single drop of in situ gel reducing the required amount of administered active ingredients by four- to eight-fold compared with classic eye drop regimen. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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16 pages, 4271 KiB

Open AccessArticle

Investigations to Evaluate Gastric Mucoadhesion of an Organic Product to Ameliorate Gastritis

by Christina Winter, Sonja Hartl, Dagmar Kolb, Gerd Leitinger and Eva Roblegg

Pharmaceutics 2020, 12(4), 331; https://doi.org/10.3390/pharmaceutics12040331 - 7 Apr 2020

Cited by 5 | Viewed by 3040

Abstract

Gastritis is an inflammatory disease leading to abdominal pain, nausea, and diarrhea. While therapy depends on etiology, adhesive agents protecting the gastric tissue represent a promising treatment option. Caricol^®-Gastro is an organic product that significantly decreased gastritic abdominal pain in a [...] Read more.

Gastritis is an inflammatory disease leading to abdominal pain, nausea, and diarrhea. While therapy depends on etiology, adhesive agents protecting the gastric tissue represent a promising treatment option. Caricol^®-Gastro is an organic product that significantly decreased gastritic abdominal pain in a recent clinical study. To investigate whether this beneficial effect can be attributed to the formation of a protective layer covering the gastric mucosa after oral application, several methods were used to determine adhesion. These include macro-rheological measurements and gastric mucin interactions, which were correlated to network formation, examined by Cryo-scanning electron microscopy technique, wettability via sessile drop method on human gastric adenocarcinoma cell layers, and ex vivo adhesion studies on gastric porcine tissue with the falling liquid film technique considering physiological conditions and Franz diffusion cells for quantification. The results showed that Caricol^®-Gastro formed a stable viscoelastic network with shear thinning properties. It exhibited high wettability and spreadability and adhered to the excised gastric mucosa. We found that oat flour, as the main ingredient of Caricol^®-Gastro, supports the gel network regarding viscoelasticity and, to a lesser extent, adhesion in a concentration dependent manner. Moreover, our data highlight that a variety of coordinated methods are required to investigate gastric adhesion. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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13 pages, 1399 KiB

Open AccessArticle

Mucoadhesive Buccal Films for Local Delivery of Lactobacillus brevis

by Angela Abruzzo, Beatrice Vitali, Francesca Lombardi, Luca Guerrini, Benedetta Cinque, Carola Parolin, Federica Bigucci, Teresa Cerchiara, Catia Arbizzani, Maria Caterina Gallucci and Barbara Luppi

Pharmaceutics 2020, 12(3), 241; https://doi.org/10.3390/pharmaceutics12030241 - 8 Mar 2020

Cited by 25 | Viewed by 3794

Abstract

The aim of this work was to prepare mucoadhesive buccal films for local release of Lactobacillus brevis CD2, which shows interesting anti-inflammatory properties due to its high levels of arginine deiminase. Hydroxypropylmethylcellulose-based films were prepared by means of a modified casting method, which [...] Read more.

The aim of this work was to prepare mucoadhesive buccal films for local release of Lactobacillus brevis CD2, which shows interesting anti-inflammatory properties due to its high levels of arginine deiminase. Hydroxypropylmethylcellulose-based films were prepared by means of a modified casting method, which allowed L. brevis CD2 loading on one side of the film, before its complete drying. Three batches of films were prepared, stored at +2–8 °C and +23–25 °C for 48 weeks and characterized in terms of physico-chemical and functional properties. For each batch, the L. brevis viable count and arginine deiminase activity were evaluated at different time points in order to assess functional property maintenance over time. Moreover, the mucoadhesive properties and ability of the films to release L. brevis CD2 were evaluated. A good survival of L. brevis CD2 was observed, particularly at the storage temperature of +2–8 °C, while the activity of arginine deiminase was maintained at both temperature values. Films showed good mucoadhesive properties and guaranteed a prolonged release of viable lactobacilli, which can be directed towards the whole buccal cavity or specific mucosa lesions. In conclusion, the proposed preparative method can be successfully employed for the production of buccal films able to release viable L. brevis CD2 cells that maintain the anti-inflammatory enzymatic activity. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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13 pages, 2338 KiB

Open AccessArticle

Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

by Margherita Falavigna, Paul C. Stein, Gøril Eide Flaten and Massimiliano Pio di Cagno

Pharmaceutics 2020, 12(2), 168; https://doi.org/10.3390/pharmaceutics12020168 - 17 Feb 2020

Cited by 35 | Viewed by 6120

Abstract

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, [...] Read more.

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, thus affecting their absorption and therapeutic effect. Therefore, the effect of the mucus layer on drug absorption has to be evaluated early in the drug-development phase, prior to in vivo studies. For this reason, we developed a simple, cost-effective and reproducible method employing UV-visible localized spectroscopy for the assessment of the interaction between mucin and drugs with different physicochemical characteristics. The mucin–drug interaction was investigated by measuring the drug relative diffusivity (D_rel) in the presence of mucin, and the method was validated by fitting experimental and mathematical data. In vitro permeability studies were also performed using the mucus-covered artificial permeation barrier (mucus–PVPA, Phospholipid Vesicle-based Permeation Assay) for comparison. The obtained results showed that the diffusion of drugs was hampered by the presence of mucin, especially at higher concentrations. This novel method proved to be suitable for the investigation on the extent of mucin–drug interaction and can be successfully used to assess the impact that the mucus layer has on drug absorption. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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12 pages, 1449 KiB

Open AccessCommunication

Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications

by Marcus Hill, Matthew Twigg, Emer A. Sheridan, John G. Hardy, J. Stuart Elborn, Clifford C. Taggart, Christopher J. Scott and Marie E. Migaud

Pharmaceutics 2019, 11(8), 379; https://doi.org/10.3390/pharmaceutics11080379 - 2 Aug 2019

Cited by 36 | Viewed by 4685

Abstract

Cystic fibrosis (CF) is a complex, potentially life-threatening disease that is most effectively treated through the administration of antibiotics (e.g., colistimethate sodium). Chronic infection with Pseudomonas aeruginosa is one of the most significant events in the pathogenesis of cystic fibrosis, and tobramycin is [...] Read more.

Cystic fibrosis (CF) is a complex, potentially life-threatening disease that is most effectively treated through the administration of antibiotics (e.g., colistimethate sodium). Chronic infection with Pseudomonas aeruginosa is one of the most significant events in the pathogenesis of cystic fibrosis, and tobramycin is the treatment of choice for those patients with chronic P. aeruginosa infection who are deteriorating despite regular administration of colistimethate sodium. Effective treatment can be challenging due to the accumulation of thickened mucus in the pulmonary environment, and here we describe the results of our investigation into the development of alginate/chitosan particles prepared via precipitation for such environments. Tobramycin loading and release from the alginate/chitosan particles was investigated, with evidence of both uptake and release of sufficient tobramycin to inhibit P. aeruginosa in vitro. Functionalisation of the alginate/chitosan particles with secretory leukocyte protease inhibitor (SLPI) was shown to help inhibit the inflammatory response associated with lung infections (via inhibition of neutrophil elastase activity) and enhance their interaction with cystic fibrosis mucus (assayed via reduction of the depth of particle penetration into the mucus) in vitro, which have prospects to enhance their efficacy in vivo. Full article

(This article belongs to the Special Issue Mucoadhesive and Mucosal Drug Delivery Systems)

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