Ocular biocompatibility and tolerance study of biodegradable polymeric micelles in the rabbit eye

Polymeric nanoparticles have been developed to improve the bioavailability of drugs applied in ocular drug delivery. However, there are few information on ocular biocompatibility of polymeric nanoparticles applied topically onto the eye. In this paper, the ocular biocompatibility and tolerance of methoxy poly(ethylene glycol)–poly(ɛ-caprolactone) (MPEG–PCL) micelles (∼50 nm) were investigated in rabbit eyes after a single intracameral and intravitreal injections. In vitro cytotoxicity assays showed that MPEG–PCL micelles had no apparent cytotoxicity against human corneal epithelial cells (HCEC), human lens epithelial cells (HLEC), and retinal pigment epithelial cells (RPE cells) at micelle concentrations of 0–2 mg/mL. After a single intracameral injection of 0.2 mL MPEG–PCL micelles (200 mg/mL) into rabbit eyes, MPEG–PCL micelles were slowly removed from aqueous humor in a period of 14 days, while the intraocular pressure (IOP) was maintained at nearly the same level for 15 days. Three days after intracameral injection, dual staining of corneal endothelium showed that the endothelial cells were nearly regular hexagon-shape with well-defined organization, similar to normal endothelial cells. Hematoxylin and eosin staining indicated that there was absence of any obvious changes in microstructure of the corneal tissue and retina after a single intracameral and intravitreal injection of 0.2 mL MPEG–PCL micelles (100 mg/mL, 150 mg/mL, and 200 mg/mL). This study provides valuable information (safety and biocompatibility) for biomedical researchers to develop MPEG–PCL micelles as candidates for ocular drug delivery.