RT Journal Article T1 Smart biodegradable hydrogels: Drug-delivery platforms for treatment of chronic ophthalmic diseases affecting the back of the eye A1 Aragón Navas, Alba A1 López-Cano, José Javier A1 Johnson, Melissa A1 Sigen, Aa A1 Vicario De La Torre, Marta A1 Andrés Guerrero, Vanesa A1 Tai, Hongyun A1 Wang, Wenxin A1 Bravo Osuna, Irene A1 Herrero Vanrell, María Del Rocío AB This paper aims to develop smart hydrogels based on functionalized hyaluronic acid (HA) and PLGA-PEG-PLGA (PLGA,poly-(DL-lactic-co-glycolic acid); PEG,polyethylene glycol) for use as intraocular drug-delivery platforms. Anti-inflammatory agent dexamethasone-phosphate (0.2 %w/v) was the drug selected to load on the hydrogels. Initially, different ratios of HA-aldehyde (HA-CHO) and thiolated-HA (HA-SH) were assayed, selecting as optimal concentrations 2 and 3 % (w/v), respectively. Optimized HA hydrogel formulations presented fast degradation (8 days) and drug release (91.46 ± 3.80 % in 24 h), thus being suitable for short-term intravitreal treatments. Different technology-based strategies were adopted to accelerate PLGA-PEG-PLGA water solubility, e.g. substituting PEG1500 in synthesis for higher molecular weight PEG3000 or adding cryopreserving substances to the buffer dissolution. PEG1500 was chosen to continue optimization and the final PLGA-PEG-PLGA hydrogels (PPP1500) were dissolved in trehalose or mannitol carbonate buffer. These presented more sustained release (71.77 ± 1.59 % and 73.41 ± 0.83 % in 24 h, respectively) and slower degradation (>14 days). In vitro cytotoxicity studies in the retinal-pigmented epithelial cell line (RPE-1) demonstrated good tolerance (viability values > 90 %). PLGA-PEG-PLGA hydrogels are proposed as suitable candidates for long-term intravitreal treatments. Preliminary wound healing studies with PLGA-PEG-PLGA hydrogels suggested faster proliferation at 8 h than controls. PB Elsevier SN 0378-5173 YR 2024 FD 2024 LK https://hdl.handle.net/20.500.14352/91676 UL https://hdl.handle.net/20.500.14352/91676 LA eng NO Aragón-Navas A, López-Cano JJ, Johnson M, A S, Vicario-de-la-Torre M, Andrés-Guerrero V, et al. Smart biodegradable hydrogels: Drug-delivery platforms for treatment of chronic ophthalmic diseases affecting the back of the eye. International Journal of Pharmaceutics 2024;649:123653. https://doi.org/10.1016/j.ijpharm.2023.123653. NO Instituto de Salud Carlos III NO European Commission NO Universidad Complutense de Madrid NO Ministerio de Ciencia e Innovación (España) DS Docta Complutense RD 6 abr 2025