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

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, we present a novel approach to ocular neovascularization treatment through utilization of polymersomes from self-assembled sphingosine-grafted hyaluronic acid (HA-Sph) amphiphilic polymers. The polymersomes are generated in spherical morphologies and sizes between 97.95 nm - 161.9 nm with homogenous size distributions. Our experiments revealed that HA-Sph polymersomes, with concentrations ≥150 μg/mL, significantly inhibit the proliferation of HUVECs, while concurrently promoting the proliferation of retinal pigment epithelial cells. The polymersomes demonstrated gradual disintegration in vitro, leading to a sustained release of sphingosine, which prolonged the inhibition of HUVEC proliferation (from 87.5% at 24 h to 35.2% viability at 96 h). The efficacy of HA-Sph polymersomes in inhibiting angiogenesis was confirmed through tube formation assay, revealing a substantial reduction in total tube length compared to the control group. Our findings also validated the ocular penetration capability of polymersomes through an 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. This article is protected by copyright. All rights reserved.