Permselectivity of Silk Fibroin Hydrogels for Advanced Drug Delivery Neurotherapies

A promising trend in tissue engineering is using biomaterials to improve the control of drug concentration in targeted tissue. These vehicular systems are of specific interest when the required treatment time window is higher than the stability of therapeutic molecules in the body. Herein, the capac...

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Detalles Bibliográficos
Autores: Fernández Serra, Rocío, Lekouaghet, Amira, Peracho, Lorena, Yonesi, Mahdi, Alcázar, Alberto, Chioua, Mourad, Marco Contelles, José Luis, Pérez Rigueiro, José, Rojo, Francisco J., Panetsos Petrova, Fivos, Guinea, Gustavo V., González Nieto, Daniel
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/118214
Acceso en línea:https://hdl.handle.net/20.500.14352/118214
Access Level:acceso abierto
Palabra clave:577.1
577.2
611.81
615.01/.03
Biopolymers
Fluorescence
Hydrogels
Molecules
Peptides and proteins
Bioquímica (Farmacia)
Biología molecular (Farmacia)
Neurociencias (Biológicas)
Farmacología (Farmacia)
Ciencias Biomédicas
2302 Bioquímica
2302.21 Biología Molecular
2490 Neurociencias
3209 Farmacología
Descripción
Sumario:A promising trend in tissue engineering is using biomaterials to improve the control of drug concentration in targeted tissue. These vehicular systems are of specific interest when the required treatment time window is higher than the stability of therapeutic molecules in the body. Herein, the capacity of silk fibroin hydrogels to release different molecules and drugs in a sustained manner was evaluated. We found that a biomaterial format, obtained by an entirely aqueous-based process, could release molecules of variable molecular weight and charge with a preferential delivery of negatively charged molecules. Although the theoretical modeling suggested that drug delivery was more likely to be driven by Fickian diffusion, the external media had a considerable influence on the release, with lipophilic organic solvents such as acetonitrile–methanol (ACN–MeOH) intensifying the release of hydrophobic molecules. Second, we found that silk fibroin could be used as a vehicular system to treat a variety of brain disorders as this biomaterial sustained the release of different factors with neurotrophic (brain-derived neurotrophic factor) (BDNF), chemoattractant (C-X-C motif chemokine 12) (CXCL12), anti-inflammatory (TGF-β-1), and angiogenic (VEGF) capacities. Finally, we demonstrated that this biomaterial hydrogel could release cholesteronitrone ISQ201, a nitrone with antioxidant capacity, showing neuroprotective activity in an in vitro model of ischemia-reoxygenation. Given the slow degradation rate shown by silk fibroin in many biological tissues, including the nervous system, our study expands the restricted list of drug delivery-based biomaterial systems with therapeutic capacity for both short- and especially long-term treatment windows and has merit for use with brain pathologies.