Thermoresponsive hydrogel loaded with nanoparticles for treatment of posterior segment eye disorders

Diseases of the posterior eye segment are difficult to treat due to barriers that limit drug penetration, making repeated intravitreal injections necessary and increasing the risk of complications. This study proposes an injectable composite drug delivery system (ic-DDS) composed of PLGA nanoparticles embedded in a thermosensitive poloxamer and hyaluronic acid (HA) based hydrogel to achieve sustained release and reduce injection frequency. Three hydrogels with different poloxamer and HA compositions were characterized. Rheological analyses after autoclave sterilization and injection through a 27G needle showed that all formulations preserved their weak-gel behavior, confirming stability of their mechanical properties. Injection force predictions were consistent with values reported for commercial ophthalmic products. The gels remained rheologically stable for at least 28 days and thermogravimetric analysis confirmed the stabilizing role of HA. Multiparticle tracking demonstrated that the hydrogels modulate NP diffusion more effectively than a simulated vitreous body, especially for HA-coated NPs. All hydrogels were biocompatible, and NPs were uptake in ARPE-19 cells. The ic-DDS shows promise as an intravitreal delivery platform. Future work will focus on optimizing the formulation for sustained release.