Novel glycopolymer hydrogels as mucosa-mimetic materials to reduce animal testing

Glycopolymer hydrogels capable of mimicking mucosal tissue in mucoadhesion testing have been designed. Liquid formulations containing mucoadhesive polymers were found to be retained on these tissues to the same extent as ex vivo gastric mucosa, when using a dynamic method of assessing mucoadhesion

Il "De viribus electricitatis in motu musculari": un'analisi dal punto di vista della fisica elettrica e dei suoi sviluppi successivi

Luigi Galvani nasce il 9 Settembre 1737 a Bologna, città in cui trascorrerà tutta la vita e nella quale condurrà i suoi studi, la sua professione e le sue ricerche. In questo elaborato intendo analizzare la sua opera più famosa che lo ha collocato in maniera decisiva sul palcoscenico scientifico: il "De viribus electricitatis in motu musculari" pubblicato dall’Istituto delle Scienze di Bologna nel 1791. In questo trattato il medico bolognese esplicita il percorso sperimentale che l’ha portato a sostenere l’ipotesi dell’esistenza dell’”elettricità animale”, nozione che ha destato grande stupore all’epoca e che ha concorso alla nascita della moderna elettrofisiologia. Nonostante l’intento dell’opera sia prettamente medico, in essa sono presenti notevoli elementi di fisica elettrica che lo rendono un testo molto interessante dal punto di vista della storia della fisica. L’analisi che viene qui presentata metterà in risalto anche le anticipazioni che possono essere colte nel testo e che riguardano sviluppi successivi inerenti l’elettrodinamica e l’elettromagnetismo

Bullous Haemorrhagic Vasculitis Associated with Adalimumab in a Child with Juvenile Idiopathic Arthritis

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Development and Characterization of Azithromycin-Loaded Microemulsions: A Promising Tool for the Treatment of Bacterial Skin Infections

In recent years, the treatment of bacterial skin infections has been considered a major healthcare issue due to the growing emergence of antibiotic-resistant strains of Staphylococcus aureus. The incorporation of antibiotics in appropriate nanosystems could represent a promising strategy, able to overcome several drawbacks of the topical treatment of infections, including poor drug retention within the skin. The present work aims to develop microemulsions containing azithromycin (AZT), a broad-spectrum macrolide antibiotic. Firstly, AZT solubility in various oils, surfactants and co-surfactants was assessed to select the main components. Subsequently, microemulsions composed of vitamin E acetate, Labrasol (R) and Transcutol (R) P were prepared and characterized for their pH, viscosity, droplet size, zeta potential and ability to release the drug and to promote its retention inside porcine skin. Antimicrobial activity against S. aureus methicillin-resistant strains (MRSA) and the biocompatibility of microemulsions were evaluated. Microemulsions showed an acceptable pH and were characterized by different droplet sizes and viscosities depending on their composition. Interestingly, they provided a prolonged release of AZT and promoted its accumulation inside the skin. Finally, microemulsions retained AZT efficacy on MRSA and were not cytotoxic. Hence, the developed AZT-loaded microemulsions could be considered as useful nanocarriers for the treatment of antibiotic-resistant infections of the skin

Crosslinked Poly(Methyl Vinyl Ether-Co-Maleic Anhydride) as Topical Vehicles for Hydrophilic and Lipophilic Drugs

Poly(methyl vinyl ether-co-maleic anhydride) crosslinked with ethylene glycol (GZ-ET), 1,4-butanediol (GZ-BUT), 1,6-exandiol (GZ-EX), 1,8-octanediol (GZ-OCT), 1,10-decanediol (GZ-DEC) or 1,12-dodecanediol (GZ-DOD) was prepared and employed as a supporting material for aqueous topical gels containing pyridoxine hydrochloride (PYCL) chosen as a hydrophilic model molecule or for O/A emulsion containing beta-carotene chosen as a hydrophobic model molecule. We analyzed the effect of the nature of the crosslinker on the permeation of hydrophilic and lipophilic vitamins through porcine skin by in vitro permeation studies. The vehicles formed by crosslinked poly(methyl vinyl ether-co-maleic anhydride) showed enhanced vitamins permeation with respect to the same vehicles formed by noncrosslinked poly(methyl vinyl ether-co-maleic anhydride) (GZ). The decrease in the crosslinker acyl chain length provides vehicles accelerating the drug permeability through the skin

Drug delivery to the brain: In situ gelling formulation enhances carbamazepine diffusion through nasal mucosa models with mucin

The objective of this work was to optimize a thermosensitive in situ gelling formulation to improve intranasal and nose-to-brain delivery of the antiepileptic drug carbamazepine (CBZ). A preliminary procedure of vehicles obtained just mixing different fractions of poloxamer 407 (P407) and poloxamer 188 (P188) revealed preparations with phase transition temperatures, times to gelation and pH values suitable for nasal delivery. Subsequently, the mucoadhesive properties of the most promising formulations were tuned by adding hydroxypropylmethylcellulose types of different viscosity grades, and the effect of the adhesive polymers was evaluated by testing in vitro time and strength of mucoadhesion on specimens of sheep nasal mucosa. The formulation that showed the greatest mucoadhesive potential in vitro, with a time and force of mucoadhesion equal to 1746,75 s and 3.66 × 10-4 N, respectively, was that composed of 22% P407, 5% P188 and 0.8% HPMC low-viscous and it was further investigated for its ability to increase drug solubility and to control the release of the drug. Lastly, the capability of the candidate vehicle to ensure drug permeation across the biomimetic membrane Permeapad®, an artificial phospholipid-based barrier with a stratified architecture, and the same barrier enriched with a mucin layer was verified. The final formulation was characterized by a pH value of 6.0, underwent gelation at 32.33◦C in 37.85 s, thus showing all the features required by in situ gelling thermosensitive preparations designed for nasal delivery and, more notably, it conserved the ability to favor drug permeation in the presence of mucin. These findings suggest that the optimized gelling system could be a promising and easy to realize strategy to improve CBZ delivery to the brain exploiting both a direct and indirect pathway

Human Lactobacillus Biosurfactants as Natural Excipients for Nasal drug Delivery of Hydrocortisone

The inclusion of a chemical permeation enhancer in a dosage form is considered an effective approach to improve absorption across the nasal mucosa. Herein we evaluated the possibility of exploiting biosurfactants (BS) produced by Lactobacillus gasseri BC9 as innovative natural excipients to improve nasal delivery of hydrocortisone (HC). BC9-BS ability to improve HC solubility and the BS mucoadhesive potential were investigated using the surfactant at a concentration below and above the critical micelle concentration (CMC). In vitro diffusion studies through the biomimetic membrane PermeaPad® and the same synthetic barrier functionalized with a mucin layer were assessed to determine BC9-BS absorption enhancing properties in the absence and presence of the mucus layer. Lastly, the diffusion study was performed across the sheep nasal mucosa using BC9-BS at a concentration below the CMC. Results showed that BC9-BS was able to interact with the main component of the nasal mucosa, and that it allowed for a greater solubilization and also permeation of the drug when it was employed at a low concentration. Overall, it seems that BC9-BS could be a promising alternative to chemical surfactants in the nasal drug delivery fiel

Association of mucoadhesive polymeric matrices and liposomes for local delivery of miconazole: A new approach for the treatment of oral candidiasis

Since the local treatment of oral candidiasis usually requires long-term administration of the antifungal drug, an ideal dosage form should be able to maintain the drug release over an extended period, assuring an adequate concentration at the infection site. In this context, we have considered the possibility of a buccal delivery of miconazole nitrate (MN) by mucoadhesive polymeric matrices. The loading of the antifungal drug in a hydrophilic matrix was made possible by taking advantage of the amphiphilic nature of liposomes (LP). The MN-loaded LP were prepared by a thin film evaporation method followed by extrusion, while solid matrices were obtained by freeze-drying a suspension of the LP in a polymeric solution based on chitosan (CH), sodium hyaluronate (HYA), or hydroxypropyl methylcellulose (HPMC). MN-loaded LP measured 284.7 +/- 20.1 nm with homogeneous size distribution, adequate drug encapsulation efficiency (86.0 +/- 3.3 %) and positive zeta potential (+47.4 +/- 3.3). CH and HYA-based formulations almost completely inhibited C. albicans growth after 24 h, even if the HYA-based one released a higher amount of the drug. The CH-based matrix also provided the best mucoadhesive capacity and therefore represents the most promising candidate for the local treatment of oral candidiasis