Biodegradable double cross-linked chitosan hydrogels for drug delivery: Impact of chemistry on rheological and pharmacological performance

This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the c...

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Detalles Bibliográficos
Autores: Iglesias Blanco, Nieves, Galbis Fuster, Elsa, Valencia, Concepción, Díaz Blanco, Manuel Jesús, Lacroix, Bertrand, Paz Báñez, María Violante de
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/154413
Acceso en línea:https://hdl.handle.net/11441/154413
https://doi.org/10.1016/j.ijbiomac.2020.10.006
Access Level:acceso abierto
Palabra clave:Ionic cross-linking
Chemical cross-linking
Controlled drug release
Biodegradable
Eco-friendly formulations
Viscoelastic hydrogels
Descripción
Sumario:This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the chosen ionic and covalent cross-linker, respectively. The novel hydrogels completely disintegrated within 96 h by means of a hydrolysis process mediated by the enzyme trehalase. As far as the authors are aware, this is the first time that a trehalose derivative has been used as a covalent cross-linker in the formation of biodegradable hydrogels. The impact of CTS concentration and degree of cov-XrL on rheological parameters were examined by means of an experimental model design and marked differences were found between the materials. Hydrogels with maximum elastic properties were achieved at high CTS concentrations and high degrees of cov-XrL. DCNa-loaded formulations displayed well-controlled drug-release profiles strongly dependent on formulation composition (from 17% to 40% in 72 h). Surprisingly, higher degrees of covalent cross-linking led to a boost in drug release. The formulations presented herein provides a simple and straightforward pathway to design fully biodegradable, tailor-made controlled drug delivery systems with improved rheological properties.