RT Journal Article
T1 Thermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseases
A1 López Cano, José Javier
A1 Sigen, Aa
A1 Andrés Guerrero, Vanesa
A1 Tai, Hongyun
A1 Bravo Osuna, Irene
A1 Molina Martínez, Irene Teresa
A1 Wang, Wenxin
A1 Herrero Vanrell, María Del Rocío
AB The present study aims to develop a thermo-responsive-injectable hydrogel (HyG) based on PLGA-PEG-PLGA (PLGA = poly-(DL-lactic acid co-glycolic acid); PEG = polyethylene glycol) to deliver neuroprotective agents to the retina over time. Two PLGA-PEG PLGA copolymers with different PEG:LA:GA ratios (1:1.54:23.1 and 1:2.25:22.5) for HyG-1 and HyG-2 development respectively were synthetized and characterized by different techniques (gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), critical micelle concentration (CMC), gelation and rheological behaviour). According to the physicochemical characterization, HyG-1 was selected for further studies and loaded with anti-inflammatory drugs: dexamethasone (0.2%), and ketorolac (0.5%), alone or in combination with the antioxidants idebenone (1 µM) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) (0.002%). In vitro drug release and cytotoxicity studies were performed for the active substances and hydrogels (loaded and drug-free). A cellular model based on oxidative stress was optimized for anti-inflammatory and antioxidant screening of the formulations by using retinal-pigmented epithelial cell line hTERT (RPE-1). The copolymer 1, used to prepare thermo-responsive HyG-1, showed low polydispersity (PDI = 1.22) and a strong gel behaviour at 25% (w/v) in an isotonic buffer solution close to the vitreous temperature (31–34 °C). Sustained release of dexamethasone and ketorolac was achieved between 47 and 62 days, depending on the composition. HyG-1 was well tolerated (84.5 ± 3.2%) in retinal cells, with values near 100% when the anti-inflammatory and antioxidant agents were included. The combination of idebenone and dexamethasone promoted high oxidative protection in the cells exposed to H2O2, with viability values of 86.2 ± 14.7%. Ketorolac and dexamethasone-based formulations ameliorated the production of TNF-α, showing significant results (p ≤ 0.0001). The hydrogels developed in the present study entail a novel biodegradable tool to treat neurodegenerative processes of the retina overtime
PB MDPI
SN 1999-4923
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/7809
UL https://hdl.handle.net/20.500.14352/7809
LA eng
NO López Cano, J. J., A. S., Andrés Guerrero, V. et al. «Thermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseases». Pharmaceutics, vol. 13, n.o 2, febrero de 2021, p. 234. https://doi.org/10.3390/pharmaceutics13020234.
NO This research was funded by Research Group UCM 920415 (InnOftal). MINECO/AEI/FEDER,UE (MAT2017-83858-C2-1-R), MSCA-RISE-3DNEONET/734907, ISCIII-FEDER RETICS (OFTARED) (RD16/0008/0009 and RD16/0008/0004).
NO Unión Europea
NO Ministerio de Economía, Comercio y Empresa (España)/Fondo Europeo de Desarrollo Regional
NO Instituto de Salud Carlos III
NO Fondo Europeo de Desarrollo Regional
NO Redes Temáticas de Investigación Cooperativa en Salud (España)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 10 abr 2025