{"title":"Peptide dendrimer and hyaluronic acid modified nanovesicles for ocular delivery of timolol maleate and siRNA.","authors":"Santoshi Naik, Naitik Jain, Nagarajan Theruveethi, Srinivas Mutalik","doi":"10.1038/s41598-025-10960-9","DOIUrl":null,"url":null,"abstract":"<p><p>Glaucoma, a leading cause of irreversible blindness, is characterized by retinal ganglion cell (RGC) degeneration due to elevated intraocular pressure (IOP) and apoptosis. While timolol maleate effectively lowers IOP, it does not prevent RGC loss and suffers from poor corneal permeability and rapid clearance. This study introduces a novel dual-delivery nanovesicular system employing multifunctional spanlastics to simultaneously lower IOP and inhibit RGC apoptosis via caspase-2 gene silencing. The system comprises two distinct nanovesicle populations: (i) timolol-loaded vesicles conjugated with peptide dendrimers to enhance corneal penetration and anterior segment delivery; and (ii) siRNA-loaded vesicles targeting Caspase-2, coated with hyaluronic acid for posterior segment delivery and gene silencing. This is the first approach integrating IOP reduction with targeted genetic intervention to protect RGCs. Formulations were optimized using a Design of Experiments approach and showed desirable physicochemical properties, sustained release, improved transcorneal permeability, and 1-month stability at 4 °C. In vitro studies confirmed Caspase-2 silencing and apoptosis reduction in RGC-5 cells, while in vivo results demonstrated prolonged IOP control. Safety was confirmed via histopathological and ocular irritation assessments. This targeted, non-invasive dual-delivery platform offers a promising therapeutic strategy for comprehensive glaucoma management.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"26074"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274417/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scientific Reports","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41598-025-10960-9","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Glaucoma, a leading cause of irreversible blindness, is characterized by retinal ganglion cell (RGC) degeneration due to elevated intraocular pressure (IOP) and apoptosis. While timolol maleate effectively lowers IOP, it does not prevent RGC loss and suffers from poor corneal permeability and rapid clearance. This study introduces a novel dual-delivery nanovesicular system employing multifunctional spanlastics to simultaneously lower IOP and inhibit RGC apoptosis via caspase-2 gene silencing. The system comprises two distinct nanovesicle populations: (i) timolol-loaded vesicles conjugated with peptide dendrimers to enhance corneal penetration and anterior segment delivery; and (ii) siRNA-loaded vesicles targeting Caspase-2, coated with hyaluronic acid for posterior segment delivery and gene silencing. This is the first approach integrating IOP reduction with targeted genetic intervention to protect RGCs. Formulations were optimized using a Design of Experiments approach and showed desirable physicochemical properties, sustained release, improved transcorneal permeability, and 1-month stability at 4 °C. In vitro studies confirmed Caspase-2 silencing and apoptosis reduction in RGC-5 cells, while in vivo results demonstrated prolonged IOP control. Safety was confirmed via histopathological and ocular irritation assessments. This targeted, non-invasive dual-delivery platform offers a promising therapeutic strategy for comprehensive glaucoma management.
期刊介绍：
We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections.
Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021).
•Engineering
Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live.
•Physical sciences
Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics.
•Earth and environmental sciences
Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems.
•Biological sciences
Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants.
•Health sciences
The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
