Citation: Rafael, D.; Guerrero, M.; Marican, A.; Arango, D.; Sarmento, B.; Ferrer, R.; Durán-Lara, E.F.; Clark, S.J.; Schwartz, S., Jr. Delivery Systems in Ocular Retinopathies: The Promising Future of Intravitreal Hydrogels as Sustained-Release Scaffolds. Pharmaceutics 2023, 15, 1484. https://doi.org/10.3390/ pharmaceutics15051484 Academic Editor: Anna Angela Barba Received: 5 April 2023 Revised: 5 May 2023 Accepted: 9 May 2023 Published: 12 May 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). pharmaceutics Review Delivery Systems in Ocular Retinopathies: The Promising Future of Intravitreal Hydrogels as Sustained-Release Scaffolds Diana Rafael 1,2,3 , Marcelo Guerrero 4,5 , Adolfo Marican 4,5,6 , Diego Arango 7,8 , Bruno Sarmento 9 , Roser Ferrer 10 , Esteban F. Durán-Lara 4,5 , Simon J. Clark 11,12,13, * and Simo Schwartz, Jr. 1,10, * 1 Drug Delivery & Targeting, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain; diana.fernandes_de_so@vhir.org 2 Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, 28029 Madrid, Spain 3 Functional Validation & Preclinical Research (FVPR), 20 ICTS Nanbiosis, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain 4 Bio & Nano Materials Lab, Drug Delivery and Controlled Release, Departamento de Microbiología, Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile; marcelo.guerrero@utalca.cl (M.G.); amarican@utalca.cl (A.M.); eduran@utalca.cl (E.F.D.-L.) 5 Center for Nanomedicine, Diagnostic & Drug Development (ND3), Universidad de Talca, Talca 3460000, Chile 6 Instituto de Química de Recursos Naturales, Universidad de Talca, Talca 3460000, Chile 7 Group of Biomedical Research in Digestive Tract Tumors, Vall d’Hebron University Hospital Research Institute (VHIR), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; darango@irblleida.cat 8 Group of Molecular Oncology, Biomedical Research Institute of Lleida (IRBLleida), 25198 Lleida, Spain 9 i3S-Instituto de Investigação e Inovação, Saúde Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; bruno.sarmento@i3s.up.pt 10 Clinical Biochemistry Group, Vall d’Hebron Hospital, 08035 Barcelona, Spain; roser.ferrer@vallhebron.cat 11 Department for Ophthalmology, University Eye Clinic, Eberhard Karls University of Tübingen, 72076 Tübingen, Germany 12 Institute for Ophthalmic Research, Eberhard Karls University of Tübingen, 72076 Tübingen, Germany 13 Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK * Correspondence: simon.clark@uni-tuebingen.de (S.J.C.); simo.schwartz@vhir.org (S.S.J.) Abstract: Slow-release delivery systems are needed to ensure long-term sustained treatments for reti- nal diseases such as age-related macular degeneration and diabetic retinopathy, which are currently treated with anti-angiogenic agents that require frequent intraocular injections. These can cause serious co-morbidities for the patients and are far from providing the adequate drug/protein release rates and required pharmacokinetics to sustain prolonged efficacy. This review focuses on the use of hydrogels, particularly on temperature-responsive hydrogels as delivery vehicles for the intravitreal injection of retinal therapies, their advantages and disadvantages for intraocular administration, and the current advances in their use to treat retinal diseases. Keywords: hydrogels; stimuli-responsive; thermo-responsive; retinopathies; delivery systems; intravitreal delivery 1. Introduction to Retinal Diseases Retinal diseases include a wide range of disorders affecting the retina, the light- sensitive tissue at the posterior of the eye. Retinal degeneration, leading to blindness, is a major disease category affecting millions of people worldwide [1]. While not lethal on its own, vision loss is known to have a major impact on the physical and mental health of patients, representing one of the top fears of patients in a recent global survey (www.theharrispoll.com (accessed on 15 April 2022)). Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are among the most common diseases that cause visual impairment affecting the posterior segment of the eye. The prevalence of moderate to Pharmaceutics 2023, 15, 1484. https://doi.org/10.3390/pharmaceutics15051484 https://www.mdpi.com/journal/pharmaceutics