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Anti\u2010VEGF treatments suffer from requiring frequent intraocular injections for effective treatment due to limited half\u2010life. This study aimed to utilize a composite nanoparticle\u2010hydrogel drug delivery system consisting of poly(glycerol sebacate) (PGS) nanoparticles and cross\u2010linked hyaluronic acid hydrogel to achieve an extended release of anti\u2010VEGF agent, HRH peptide, with the objective of reducing the frequency of intravitreal injections required for treatment of neovascular diseases. Our findings reveal a promising 42.54% \u00b1 5.99% drug release from HA\u2010PGS NP@HRH within the first 3 months, indicating potential for sustained drug release applications. Cell viability studies demonstrate biocompatibility with human retinal pigment epithelium (ARPE\u201019) cells and reveal anti\u2010angiogenic effects by binding to VEGF receptors on human umbilical vein endothelial (HUVEC) cells, inhibiting VEGF activity, cell growth (with 55.19% cell viability), and tube formation of HUVECs. In vivo experiments with an oxygen\u2010induced retinopathy (OIR) model demonstrated a suppression of neovascularization in mice treated with PGS NPs@HRH. Our research strives to contribute to the development of these new\u2010generation materials, promising improved treatment efficacy and ultimately enhancing the quality of life for patients affected by these challenging conditions.<\/jats:p>","DOI":"10.1002\/mabi.202500263","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T08:30:17Z","timestamp":1768379417000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of Nanoparticle\u2010Hydrogel Drug Delivery System for Sustained Release of Anti\u2010VEGF Peptide in Ocular Neovascularization Treatment"],"prefix":"10.1002","volume":"26","author":[{"given":"Saliha","family":"Durak","sequence":"first","affiliation":[{"name":"Nanotechnology Research and Application Center (SUNUM) Sabanci University  Istanbul Turkey"},{"name":"Faculty of Engineering and Natural Sciences Molecular Biology, Genetics and Bioengineering Program Sabanci University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abuzer Alp","family":"Yetisgin","sequence":"additional","affiliation":[{"name":"Nanotechnology Research and Application Center (SUNUM) Sabanci University  Istanbul Turkey"},{"name":"Faculty of Engineering and Natural Sciences Materials Science and Nano\u2010Engineering Program Sabanci University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysegul","family":"Aciksari","sequence":"additional","affiliation":[{"name":"Nanotechnology Research and Application Center (SUNUM) Sabanci University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramazan","family":"Ceylan","sequence":"additional","affiliation":[{"name":"Nanotechnology Research and Application Center (SUNUM) Sabanci University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ecem","family":"Onder Tokuc","sequence":"additional","affiliation":[{"name":"Kocaeli University School of Medicine Department of Ophthalmology  Kocaeli Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozlem","family":"Kutlu","sequence":"additional","affiliation":[{"name":"Nanotechnology Research and Application Center (SUNUM) Sabanci University  Istanbul Turkey"},{"name":"Faculty of Engineering and Natural Sciences Molecular Biology, Genetics and Bioengineering Program Sabanci University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veysel Levent","family":"Karabas","sequence":"additional","affiliation":[{"name":"Kocaeli University School of Medicine Department of Ophthalmology  Kocaeli Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0248-9447","authenticated-orcid":false,"given":"Sibel","family":"Cetinel","sequence":"additional","affiliation":[{"name":"Nanotechnology Research and Application Center (SUNUM) Sabanci University  Istanbul Turkey"},{"name":"Faculty of Engineering and Natural Sciences Molecular Biology, Genetics and Bioengineering Program Sabanci University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"J.Ambati B. 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