Biocompatibility and safety of insulin-loaded chitosan nanoparticles/PLGAPEG-PLGA hydrogel (ICNPH) delivered by subconjunctival injection in rats

Ocular drug delivery, specifically protein drug delivery to the posterior segment of the eye, remains a challenge. The purpose of this study was to prepare a new double-controlled drug release system (with insulin as the drug) for ocular delivery via subconjunctival injection and to investigate its ocular biocompatibility and safety. The double-controlled release system, insulin-loaded nanoparticles/PLGA-PEG-PLGA hydrogel (ICNPH) was prepared by adding insulin-loaded chitosan nanoparticles (ICN) to PLGA-PEG-PLGA hydrogel. The characteristics of the ICN were determined by dynamic light scattering and scanning electron microscopy. HPLC was used to analyze the loading content and insulin release profile of the ICNPH. The ICN were found to be globular particles with a mean diameter of 137.5 nm and 12% loading content. The sustained release of insulin from the ICNPH lasted for more than 60 days. Electroretinograms, retinal ultrastructure and microstructure, retinal cell apoptosis and glial fibrillary acidic protein expression were examined to assess retinal injury caused by the ICNPH after subconjunctival injection. The results showed no obvious damage to retinal function, structure and neurons. Therefore, the ICNPH is biocompatible and safe via subconjunctival injection, and may be a candidate for ocular drug delivery.