Hyaluronan-Sphingosine Polymersomes for Treatment of Ocular Neovascularization: Synthesis and Evaluation.

Autor: Yetisgin AA; Nanotechnology Research and Application Center (SUNUM), Sabanci University, Istanbul, 34956, Turkey.; Faculty of Engineering and Natural Sciences, Materials Science and Nano-Engineering Program, Sabanci University, Istanbul, 34956, Turkey., Durak S; Nanotechnology Research and Application Center (SUNUM), Sabanci University, Istanbul, 34956, Turkey.; Faculty of Engineering and Natural Sciences, Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, 34956, Turkey., Kutlu O; Nanotechnology Research and Application Center (SUNUM), Sabanci University, Istanbul, 34956, Turkey.; Faculty of Engineering and Natural Sciences, Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, 34956, Turkey., Cetinel S; Nanotechnology Research and Application Center (SUNUM), Sabanci University, Istanbul, 34956, Turkey.; Faculty of Engineering and Natural Sciences, Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, 34956, Turkey.
Jazyk: angličtina
Zdroj: Macromolecular bioscience [Macromol Biosci] 2024 Jun; Vol. 24 (6), pp. e2300531. Date of Electronic Publication: 2024 Feb 13.
DOI: 10.1002/mabi.202300531
Abstrakt: Ocular neovascularization is a hallmark of several sight-threatening diseases, including diabetic retinopathy and age-related macular degeneration. Currently, available treatments are limited and often associated with side effects. Therefore, a novel approach to ocular neovascularization treatment through utilization of polymersomes from self-assembled sphingosine-grafted hyaluronic acid (HA-Sph) amphiphilic polymers is presented. The polymersomes are generated in spherical morphologies and sizes between 97.95 - 161.9 nm with homogenous size distributions. Experiments reveal that HA-Sph polymersomes, with concentrations ≥150 µg mL -1 , significantly inhibit the proliferation of human umbilical vein endothelial cells (HUVECs), while concurrently promoting the proliferation of retinal pigment epithelial cells. The polymersomes demonstrate gradual disintegration in vitro, leading to sustained release of sphingosine, which prolongs the inhibition of HUVEC proliferation (from 87.5% at 24 h to 35.2% viability at 96 h). The efficacy of polymersomes in inhibiting angiogenesis is confirmed through tube formation assay, revealing a substantial reduction in tube length compared to the control group. The findings also validate the ocular penetration capability of polymersomes through ex vivo whole porcine eye ocular penetration study, indicating their suitability for topical administration. Potentially, HA-Sph polymersomes can be harnessed to develop intricate drug delivery systems that protect the retina and effectively treat ocular diseases.
(© 2024 The Authors. Macromolecular Bioscience published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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