Abstract
Purpose :
Filtration surgery is primary treatment for advanced glaucoma, but its success is limited by fibrosis. To enhance the success rate, we aim to develop a novel hydrogel that is safe and patient-friendly. It can serve as an adjunct during surgery, preventing fibrosis and reducing the need for repeat surgeries.
Methods :
Poly-2-oxazolines (POx)-based ABA triblock copolymers were synthesized as reported earlier. Cytocompatibility was assessed by XTT assay on primary cells. Micelles were prepared via liquid dispersion method with various polymer-to-dexamethasone (DEX) ratios. Drug loading was determined by UV-Vis spectroscopy and size analysis by dynamic light scattering. Micelles were visualized through negative staining and cryo-scanning electron microscopy. The hydrogel was prepared using an acrylate-based derivative of hyaluronic acid (HAA). Along with photo-initiators within the visible light spectrum, it can be set to hydrogel in under 60 seconds. The stability studies (hours to weeks) of the micellar formulation were conducted. The hydrogel was also tested to demonstrate that cells could not adhere to it (FDA and Hoechst staining). The bioadhesive nature of the hydrogel was investigated on porcine sclera.
Results :
POx-based ABA triblock copolymer showed no signs of cytotoxicity (cell viability > 95%), even at highest concentration of 50 g/L. The triblock copolymer solublized around 4.8 ± 0.18 g/L of DEX (loading capacity 30 wt.% and loading efficiency 80%). The micelle size was 20-30 nm and appeared spherical. The HAA showed a porous morphology under cryo-SEM. The HAA hydrogel non-cell adhesive property was studied, revealing the creation of an interface between cells and the hydrogel surface. The HAA hydrogel is injectable and exhibited fast crosslinking, making its use ideal for applications in fast-gelling hydrogel systems at the surgical site. This is demonstrated by employing the hydrogels on the defect on the porcine sclera followed by crosslinking. The bioadhesive nature was confirmed under a stream of water.
Conclusions :
We have demonstrated HAA-based hydrogels loaded with DEX-POx micelles. These hydrogels are non-cell adhesive but offer bio-adhesiveness during crosslinking. They can potentially be used as an adjunct in glaucoma filtration surgery. However, this warrants further detailed preclinical investigation.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.