Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration

Abstract

Jingguo Li, Zhanrong Li, Tianyang Zhou, Junjie Zhang, Huiyun Xia, Heng Li, Jijun He, Siyu He, Liya Wang Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital and Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China Purpose: The cornea is a main barrier to drug penetration after topical application. The aim of this study was to evaluate the abilities of micelles generated from a positively charged triblock copolymer to penetrate the cornea after topical application. Methods: The triblock copolymer poly(ethylene glycol)-poly(ε-caprolactone)-g-polyethyleneimine was synthesized, and the physicochemical properties of the self-assembled polymeric micelles were investigated, including hydrodynamic size, zeta potential, morphology, drug-loading content, drug-loading efficiency, and in vitro drug release. Using fluorescein diacetate as a model drug, the penetration capabilities of the polymeric micelles were monitored in vivo using a two-photon scanning fluorescence microscopy on murine corneas after topical application. Results: The polymer was successfully synthesized and confirmed using nuclear magnetic resonance and Fourier transform infrared. The polymeric micelles had an average particle size of 28 nm, a zeta potential of approximately +12 mV, and a spherical morphology. The drug-loading efficiency and drug-loading content were 75.37% and 3.47%, respectively, which indicates that the polymeric micelles possess a high drug-loading capacity. The polymeric micelles also exhibited controlled-release behavior in vitro. Compared to the control, the positively charged polymeric micelles significantly penetrated through the cornea. Conclusion: Positively charged micelles generated from a triblock copolymer are a promising vehicle for the topical delivery of hydrophobic agents in ocular applications. Keywords: corneal barriers, polymeric micelles, topical administration, corneal penetration, controlled release