RT Journal Article T1 Permselectivity of Silk Fibroin Hydrogels for Advanced Drug Delivery Neurotherapies A1 Fernández Serra, Rocío A1 Lekouaghet, Amira A1 Peracho, Lorena A1 Yonesi, Mahdi A1 Alcázar, Alberto A1 Chioua, Mourad A1 Marco Contelles, José Luis A1 Pérez Rigueiro, José A1 Rojo, Francisco J. A1 Panetsos Petrova, Fivos A1 Guinea, Gustavo V. A1 González Nieto, Daniel AB 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. PB DC American Chemical Society SN 1525-7797 YR 2024 FD 2024-07-17 LK https://hdl.handle.net/20.500.14352/118214 UL https://hdl.handle.net/20.500.14352/118214 LA eng NO Fernández-Serra, R., Lekouaghet, A., Peracho, L., Yonesi, M., Alcázar, A., Chioua, M., Marco-Contelles, J., Pérez-Rigueiro, J., Rojo, FJ, Panetsos, F., Guinea, GV, & González-Nieto, D. (2024). Permeabilidad selectiva de hidrogeles de fibroína de seda para neuroterapias de administración avanzada de fármacos. Biomacromoléculas , 25 (8), 5233-5250. https://doi.org/10.1021/ACS.BIOMAC.4C00629 NO Ministerio de Ciencia e Innovación (España) NO Comunidad de Madrid NO European Commission NO Instituto de Salud Carlos III DS Docta Complutense RD 27 abr 2025