Thermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseases

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dc.contributor.authorLópez Cano, José Javier
dc.contributor.authorA, Sigen
dc.contributor.authorAndrés Guerrero, Vanesa
dc.contributor.authorTai, Hongyun
dc.contributor.authorBravo Osuna, Irene
dc.contributor.authorMolina Martínez, Irene Teresa
dc.contributor.authorWang, Wenxin
dc.contributor.authorHerrero Vanrell, María Del Rocío
dc.date.accessioned2023-06-17T08:58:59Z
dc.date.available2023-06-17T08:58:59Z
dc.date.issued2021-02-07
dc.descriptionThis 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).
dc.description.abstractThe 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 overtimeen
dc.description.departmentDepto. de Farmacia Galénica y Tecnología Alimentaria
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipUnión Europea
dc.description.sponsorshipMinisterio de Economía, Comercio y Empresa (España)/Fondo Europeo de Desarrollo Regional
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipFondo Europeo de Desarrollo Regional
dc.description.sponsorshipRedes Temáticas de Investigación Cooperativa en Salud (España)
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/64032
dc.identifier.citationLópez 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. DOI.org (Crossref), https://doi.org/10.3390/pharmaceutics13020234.
dc.identifier.doi10.3390/pharmaceutics13020234
dc.identifier.issn1999-4923
dc.identifier.officialurlhttps//doi.org/10.3390/pharmaceutics13020234
dc.identifier.relatedurlhttps://www.mdpi.com/journal/pharmaceutics
dc.identifier.urihttps://hdl.handle.net/20.500.14352/7809
dc.issue.number2
dc.journal.titlePharmaceutics
dc.language.isoeng
dc.publisherMDPI
dc.relation.projectID3D NEONET (734907)
dc.relation.projectIDUCM 920415 (InnOftal)
dc.relation.projectID(MAT2017-83858-C2-1-R)
dc.relation.projectID(OFTARED) (RD16/0008/0009 and RD16/0008/0004)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.keywordPLGA-PEG-PLGA
dc.subject.keywordThermo-responsive hydrogel
dc.subject.keywordMicelles
dc.subject.keywordNeurodegenerative diseases
dc.subject.keywordIntravitreal drug delivery
dc.subject.keywordOxidative stress
dc.subject.keywordInflammation
dc.subject.keywordKetorolac
dc.subject.keywordDexamethasone
dc.subject.ucmQuímica orgánica (Química)
dc.subject.ucmTecnología farmaceútica
dc.subject.unesco2306 Química Orgánica
dc.titleThermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseasesen
dc.typejournal article
dc.volume.number13
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscovery491381a5-fc5a-4cd5-a0b0-9b6cfdae6706
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