Novel antipsoriatic fluidized spanlastic nanovesicles: In vitro physicochemical characterization, ex vivo cutaneous retention and exploratory clinical therapeutic efficacy

2019 ◽  
Vol 568 ◽  
pp. 118556 ◽  
Author(s):  
Enas Elmowafy ◽  
Riham I. El-Gogary ◽  
Maha H. Ragai ◽  
Maha Nasr
Keyword(s):  
Therapeutic Efficacy ◽  
Ex Vivo ◽  
Physicochemical Characterization

scholarly journals Nanocrystals of Fusidic Acid for Dual Enhancement of Dermal Delivery and Antibacterial Activity: In Vitro, Ex Vivo and In Vivo Evaluation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 199 ◽  
Author(s):  
Iman S. Ahmed ◽  
Osama S. Elnahas ◽  
Nouran H. Assar ◽  
Amany M. Gad ◽  
Rania El Hosary
Keyword(s):  
Fusidic Acid ◽  
Therapeutic Efficacy ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Fold Increase ◽  
Spherical Particles ◽  
Resistant Bacteria ◽  
Infection Model

With the alarming rise in incidence of antibiotic-resistant bacteria and the scarcity of newly developed antibiotics, it is imperative that we design more effective formulations for already marketed antimicrobial agents. Fusidic acid (FA), one of the most widely used antibiotics in the topical treatment of several skin and eye infections, suffers from poor water-solubility, sub-optimal therapeutic efficacy, and a significant rise in FA-resistant Staphylococcus aureus (FRSA). In this work, the physico-chemical characteristics of FA were modified by nanocrystallization and lyophilization to improve its therapeutic efficacy through the dermal route. FA-nanocrystals (NC) were prepared using a modified nanoprecipitation technique and the influence of several formulation/process variables on the prepared FA-NC characteristics were optimized using full factorial statistical design. The optimized FA-NC formulation was evaluated before and after lyophilization by several in-vitro, ex-vivo, and microbiological tests. Furthermore, the lyophilized FA-NC formulation was incorporated into a cream product and its topical antibacterial efficacy was assessed in vivo using a rat excision wound infection model. Surface morphology of optimized FA-NC showed spherical particles with a mean particle size of 115 nm, span value of 1.6 and zeta potential of −11.6 mV. Differential scanning calorimetry and powder X-ray diffractometry confirmed the crystallinity of FA following nanocrystallization and lyophilization. In-vitro results showed a 10-fold increase in the saturation solubility of FA-NC while ex-vivo skin permeation studies showed a 2-fold increase in FA dermal deposition from FA-NC compared to coarse FA. Microbiological studies revealed a 4-fofd decrease in the MIC against S. aureus and S. epidermidis from FA-NC cream compared to commercial Fucidin cream. In-vivo results showed that FA-NC cream improved FA distribution and enhanced bacterial exposure in the infected wound, resulting in increased therapeutic efficacy when compared to coarse FA marketed as Fucidin cream.

scholarly journals Influence of injectable microparticle size on cardiac progenitor cell response

2018 ◽  
Vol 16 (4) ◽  
pp. 241-251 ◽  
Author(s):  
Elisabetta Rosellini ◽  
Niccoletta Barbani ◽  
Caterina Frati ◽  
Denise Madeddu ◽  
Diana Massai ◽  
...  
Keyword(s):  
Cell Response ◽  
Progenitor Cell ◽  
Ex Vivo ◽  
Physicochemical Characterization ◽  
Hydrolytic Degradation ◽  
Spherical Shape ◽  
Oil Emulsion ◽  
Cardiac Progenitor Cell ◽  
Injectable Scaffolds

Introduction: Injectable scaffolds are emerging as a promising strategy in the field of myocardial tissue engineering. Among injectable scaffolds, microparticles have been poorly investigated. The goal of this study was the development of novel gelatin/gellan microparticles that could be used as an injectable scaffold to repair the infarcted myocardium. In particular, the effect of particle size on cardiac progenitor cell response was investigated. Methods: Particles were produced by a water-in-oil emulsion method. Phosphatidylcholine was used as a surfactant. Particles with different diameter ranges (125–300 µm and 350–450 µm) were fabricated using two different surfactant concentrations. Morphological, physicochemical, and functional characterizations were carried out. Cardiac progenitor cell adhesion and growth on microparticles were tested both in static and dynamic suspension culture conditions. Results: Morphological analysis of the produced particles showed a spherical shape and porous surface. The hydrophilicity of particle matrix and the presence of intermolecular interactions between gellan and gelatin were pointed out by the physicochemical characterization. A weight loss of 75 ± 5 % after 90 days of hydrolytic degradation was observed. Injectability through a narrow needle (26 G) and persistence of the microparticles at the injection site were preliminarily verified by ex vivo test. In vitro cell culture tests showed a preservation of rat cardiac progenitor biologic properties and indicated a preferential cell adherence to microparticles with a smaller size. Conclusion: Overall, the obtained results indicate that the produced gelatin/gellan microparticles could be potentially employed as injectable scaffolds for myocardial regeneration.

scholarly journals Formulation Strategies, Characterization, and In Vitro Evaluation of Lecithin-Based Nanoparticles for siRNA Delivery

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Sebastián Ezequiel Pérez ◽  
Yamila Gándola ◽  
Adriana Mónica Carlucci ◽  
Lorena González ◽  
Daniel Turyn ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Sirna Delivery ◽  
Physicochemical Characterization ◽  
Human Breast ◽  
Efficient Delivery ◽  
Interfering Rna ◽  
Mcf 7

The aim of the present work was to take advantage of lecithin’s biocompatibility along with its physicochemical properties for the preparation of lecithin-based nanocarriers for small interfering RNA (siRNA) delivery. Water lecithin dispersions were prepared in different conditions, loaded with siRNA at different N/P ratios, and evaluated for loading capacity. The most appropriate ones were then assayed for cytotoxicity and characterized in terms of particle size distribution, zeta potential, and morphology. Results demonstrated that formulations prepared at pH 5.0 and 7.0 were able to load siRNA at broad N/P ratios, and cellular uptake assays showed an efficient delivery of oligos in MCF-7 human breast cancer cells; fluorescent-labeled dsRNA mainly located next to its target, near the nucleus of the cells. No signs of toxicity were observed for broad compositions of lecithin. The physicochemical characterization of the siRNA-loaded dispersions exhibited particles of nanometric sizes and pH-dependant shapes, which make them suitable for ex vivo and in vivo further evaluation.

scholarly journals Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-β-Cyclodextrin Inclusion Complex †

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 531 ◽  
Author(s):  
Valentina Venuti ◽  
Vincenza Crupi ◽  
Barbara Fazio ◽  
Domenico Majolino ◽  
Giuseppe Acri ◽  
...  
Keyword(s):  
Fourier Transform ◽  
Inclusion Complex ◽  
Water Solubility ◽  
Ex Vivo ◽  
Morphological Changes ◽  
Physicochemical Characterization ◽  
Infrared Light ◽  
Phase Solubility ◽  
Theoretical Approaches

Idebenone (IDE) is an antioxidant drug active at the level of the central nervous system (CNS), whose poor water solubility limits its clinical application. An IDE/2-hydroxypropyl-β-cyclodextrin (IDE/HP-β-CD) inclusion complex was investigated by combining experimental methods and theoretical approaches. Furthermore, biological in vitro/ex vivo assays were performed. Phase solubility studies showed an AL type diagram, suggesting the presence of a 1:1 complex with high solubility. Scanning electron microscopy (SEM) allowed us to detect the morphological changes upon complexation. The intermolecular interactions stabilizing the inclusion complex were experimentally characterized by exploring the complementarity of Fourier-transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) with mid-infrared light, Fourier-transform near-infrared (FT-NIR) spectroscopy, and Raman spectroscopy. From the temperature evolution of the O–H stretching band of the complex, the average enthalpy ΔHHB of the hydrogen bond scheme upon inclusion was obtained. Two-dimensional (2D) rotating frame Overhauser effect spectroscopy (ROESY) analysis and computational studies involving molecular modeling and molecular dynamics (MD) simulation demonstrated the inclusion of the quinone ring of IDE inside the CD ring. In vitro/ex vivo studies evidenced that complexation produces a protective effect of IDE against the H2O2-induced damage on human glioblastoma astrocytoma (U373) cells and increases IDE permeation through the excised bovine nasal mucosa.

scholarly journals Topical Amphotericin B Semisolid Dosage Form for Cutaneous Leishmaniasis: Physicochemical Characterization, Ex Vivo Skin Permeation and Biological Activity

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 149 ◽  
Author(s):  
Diana Berenguer ◽  
Maria Magdalena Alcover ◽  
Marcella Sessa ◽  
Lyda Halbaut ◽  
Carme Guillén ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Amphotericin B ◽  
Cell Lines ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Physicochemical Characterization ◽  
Keratinocyte Cell ◽  
Permeation Studies

Amphotericin B (AmB) is a potent antifungal successfully used intravenously to treat visceral leishmaniasis but depending on the Leishmania infecting species, it is not always recommended against cutaneous leishmaniasis (CL). To address the need for alternative topical treatments of CL, the aim of this study was to elaborate and characterize an AmB gel. The physicochemical properties, stability, rheology and in vivo tolerance were assayed. Release and permeation studies were performed on nylon membranes and human skin, respectively. Toxicity was evaluated in macrophage and keratinocyte cell lines, and the activity against promastigotes and intracellular amastigotes of Leishmania infantum was studied. The AmB gel remained stable for a period of two months, with optimal properties for topical use and no apparent toxic effect on the cell lines. High amounts of AmB were found in damaged and non-damaged skin (1230.10 ± 331.52 and 2484.57 ± 439.12 µg/g/cm2, respectively) and they were above the IC50 of AmB for amastigotes. Although there were no differences in the in vitro anti-leishmanial activity between the AmB solution and gel, the formulation resulted in a higher amount of AmB being retained in the skin, and is therefore a candidate for further studies of in vivo efficacy.

scholarly journals Formulation and Evaluation of Eudragit RL-100 Nanoparticles Loaded In-Situ Forming Gel for Intranasal Delivery of Rivastigmine

2019 ◽  
Vol 10 (1) ◽  
pp. 20-29 ◽  
Author(s):  
Sara Salatin ◽  
Jaleh Barar ◽  
Mohammad Barzegar-Jalali ◽  
Khosro Adibkia ◽  
Mitra Alami-Milani ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Ex Vivo ◽  
Spherical Shape ◽  
Physicochemical Characteristics ◽  
In Vitro Cytotoxicity ◽  
Scanning Calorimetry ◽  
In Situ Forming Gel ◽  
Eudragit Rl

Purpose: Rivastigmine hydrogen tartrate (RHT) is commonly used for the treatment of mild to moderate Alzheimer’s disease (AD). The aim of this work was to formulate in-situ pluronic F-127 (PF-127) hydrogels containing Eudragit RL-100 (EU-RL) nanoparticles (NPs) in order to improve the therapeutic efficacy of RHT through the nasal route. Methods: The NPs were prepared using different polymer to drug ratios and evaluated for their physicochemical characteristics, cellular uptake and in vitro cytotoxicity against lung adenocarcinoma cells (A459). PF-127 nanoformulations were prepared via cold method and analyzed in terms of physicochemical properties and drug release profiles. The nanoformulations and plain drug gel were then assessed by ex vivo permeation studies across the sheep nasal mucosa. Results: The EU-RL NPs exhibited a particle size within the range of 118 to 154 nm and positive zeta potential values of 22.5 to 30 mV with an approximately spherical shape. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) suggested no drug to polymer interaction through the preparation of nanoformulations. The RHT-loaded NPs exhibited an acceptable cytocompatibility with a time- and dose-dependent cellular internalization. Conclusion: Our results clearly indicated the potential of nanoformulations as controlled release systems to improve the therapeutic efficacy of RHT through the intranasal administration

scholarly journals Ocular Co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation

2020 ◽  
Vol 13 (6) ◽  
pp. 126
Author(s):  
Elissavet Taka ◽  
Christina Karavasili ◽  
Nikolaos Bouropoulos ◽  
Thomas Moschakis ◽  
Dimitrios D. Andreadis ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Patient Adherence ◽  
Ex Vivo ◽  
Physicochemical Characterization ◽  
Corneal Permeability ◽  
Force Microscopy ◽  
Glaucoma Therapy ◽  
Self Assembling ◽  
Hydrogel Matrix

Effective pharmacotherapy during glaucoma treatment depends on interventions that reduce intraocular pressure (IOP) and retain the IOP lowering effect for sufficient time so as to reduce dosing frequency and enhance patient adherence. Combination anti-glaucoma therapy and dosage forms that increase precorneal residence time could therefore constitute a promising therapeutic intervention. The in-situ gel forming self-assembling peptide ac-(RADA)4-CONH2 was evaluated as carrier for the ocular co-delivery of timolol maleate (TM) and brimonidine tartrate (BR). The hydrogel’s microstructure and mechanical properties were assessed with atomic force microscopy and rheology, respectively. Drug diffusion from the hydrogel was evaluated in vitro in simulated tear fluid and ex vivo across porcine corneas and its effect on the treated corneas was assessed through physicochemical characterization and histological analysis. Results indicated that TM and BR co-delivery affected hydrogel’s microstructure resulting in shorter nanofibers and a less rigid hydrogel matrix. Rapid and complete release of both drugs was achieved within 8 h, while a 2.8-fold and 5.4-fold higher corneal permeability was achieved for TM and BR, respectively. No significant alterations were induced in the structural integrity of the corneas treated with the hydrogel formulation, suggesting that self-assembling peptide hydrogels might serve as promising systems for combination anti-glaucoma therapy.

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