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, 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.

Niosomal Drug Delivery Systems for Ocular Disease-Recent Advances and Future Prospects.

The eye is a complex organ consisting of several protective barriers and particular defense mechanisms. Since this organ is exposed to various infections, genetic disorders, and visual impairments it is essential to provide necessary drugs through the appropriate delivery routes and vehicles. The topical route of administration, as the most commonly used approach, maybe inefficient due to low drug bioavailability. New generation safe, effective, and targeted drug delivery systems based on nanocarriers have the capability to circumvent limitations associated with the complex anatomy of the eye. Nanotechnology, through various nanoparticles like niosomes, liposomes, micelles, dendrimers, and different polymeric vesicles play an active role in ophthalmology and ocular drug delivery systems. Niosomes, which are nano-vesicles composed of non-ionic surfactants, are emerging nanocarriers in drug delivery applications due to their solution/storage stability and cost-effectiveness. Additionally, they are biocompatible, biodegradable, flexible in structure, and suitable for loading both hydrophobic and hydrophilic drugs. These characteristics make niosomes promising nanocarriers in the treatment of ocular diseases. Hereby, we review niosome based drug delivery approaches in ophthalmology starting with different preparation methods of niosomes, drug loading/release mechanisms, characterization techniques of niosome nanocarriers and eventually successful applications in the treatment of ocular disorders.

Enhanced antibacterial and antiparasitic activity of multifunctional polymeric nanoparticles.

Due to the resistance to drugs, studies involving the combination and controlled release of different agents are gradually increasing. In this study, two different active ingredients, known to have antibacterial and antiparasitic activities, were encapsulated into single polymeric nanoparticles. After co-encapsulation their antibacterial and antileishmanial activity was enhanced approximately 5 and 250 times, respectively. Antibacterial and antileishmanial activities of caffeic acid phenethyl ester and juglone loaded, multifunctional nanoformulations (CJ4-CJ6-CJ8) were also evaluated for the first time in the literature comparatively with their combined free formulations. The antibacterial activity of the multifunctional nanoformulation (CJ8) were found to have a much higher activity (MIC values 6.25 and 12.5 µg ml-1 for S. aureus and E. coli, respectively) than all other formulations. Similar efficacy for CJ8 was obtained in the antiparasitic study against the Leishmania promastigotes and the IC50 was reduced to 0.1263 µg ml-1. The high activity of multifunctional nanoparticles is not only due to the synergistic effect of the active molecules but also by the encapsulation into polymeric nanoparticles. Therefore, it has been shown in the literature for the first time that the biological activity of molecules whose activity is increased by the synergistic effect can be improved with nanosystems.