RESUMEN
An amphiphilic chitosan salt, chitosan oleate (CS-OA), was previously proposed for the physical stabilization of lemongrass antimicrobial nanoemulsions (NE) through a mild spontaneous emulsification process. As both chitosan and oleic acid are described in the literature for their positive effects in wound healing, in the present study CS-OA has been proposed to encapsulate alpha tocopherol (αTph) in NEs aimed to skin wounds. A NE formulation was developed showing about 220â¯nm dimensions, 36% drug loading, and αTph concentration up to 1â¯mg/ml. Both CS-OA and αTph NE stimulated cell proliferation on keratinocytes and fibroblast cell cultures, and in ex vivo skin biopsies, suggesting the suitability of CS-OA and of the antioxidant agent for topical application in wound healing. αTph stability was further improved with respect of encapsulation, by spray drying the NE into a powder (up to about 90% αTph residual after 3â¯months). The spray drying process was optimized, to improve powder yield and αTph recovery, by a design of experiments approach. The powder obtained was easily re-suspended to deliver the NE and resulted able to completely release αTph.
Asunto(s)
Quitosano/química , Emulsiones/administración & dosificación , Nanopartículas/administración & dosificación , Nanopartículas/química , Ácido Oléico/química , Cicatrización de Heridas/efectos de los fármacos , alfa-Tocoferol/administración & dosificación , Antibacterianos/administración & dosificación , Antibacterianos/química , Antioxidantes/metabolismo , Biopsia , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos/métodos , Emulsiones/química , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Tamaño de la Partícula , Polvos/administración & dosificación , Polvos/química , alfa-Tocoferol/químicaRESUMEN
Different substitution degrees of palmitoyl glycol chitosan (PGC), prepared according to the literature, were used to obtain polymeric micelles that have been assessed in comparison with Pluronic F127 micelles as possible carriers for poorly soluble drugs, such as cyclosporine A. Both PGC and Pluronic micelles were studied for their interactions with cell culture substrates. The least substituted and most hydrophilic derivative, PGC21 (approximately 5% substitution), showed a strong association with cyclosporine, more than tripling the colloidal concentration with respect to the saturated solution. It showed a greater ability to open Caco-2 tight junctions and to enhance the permeability of Caco-2 substrates with respect to micelles based on higher palmitoyl substitution, conceivably due to the lower modification of the chitosan chains. Permeation and penetration experiments were performed with PGC21 and Pluronic micelles on a rabbit corneal epithelial cell line (RCE) and on excised pig corneas. It was found that both PGC and Pluronic micelles could increase the permeation of the fluorescent probe rhodamine B through RCE cells by more than ten-fold. In RCE and in pig cornea, the micelles improved the penetration of both rhodamine and cyclosporine. For cyclosporine, the PGC21 micelles allowed penetration of approximately 1 µg/mg cyclosporine A in corneal tissue, demonstrating a potential for use in immunosuppression therapies.
Asunto(s)
Quitosano/química , Córnea/química , Ciclosporina/administración & dosificación , Ciclosporina/química , Nanocápsulas/química , Animales , Difusión , Inmunosupresores/administración & dosificación , Inmunosupresores/química , Inyecciones Intraoculares , Micelas , Nanocápsulas/administración & dosificación , PorcinosRESUMEN
Chitosan is well known for its positive properties in wound healing. Also unsaturated fatty acids are described as able to accelerate tissue repairing mechanisms. In this work hydrophobically modified chitosan was obtained by ionic interaction with either oleic or linoleic acid. In aqueous environment self-assembling into nanoparticles occurred. The presence of hydrophobic domains, similar to those present in polymeric micelles, was demonstrated by changes in pyrene spectra. Both oleate and linoleate derivatives showed mucoadhesion behaviour. Cytotoxicity tests on human dermal fibroblasts demonstrated good biocompatibility of especially oleate derivatives. Clarithromycin, a poorly soluble model drug proposed for use in infected wounds was successfully encapsulated in both oleic and linoleic based polymeric micelles. The ionic structure of the carriers is responsible for their loosening at neutral pH and in the presence of salts. This behaviour should impair parenteral administration of the systems, but can be useful for topical delivery where the micelle components, chitosan and fatty acid, can play a positive role in dermal regeneration and tissue repairing.