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

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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.




Li, J., Li, Z., Zhou, T., Zhang, J., Xia, H., Li, H., … Wang, L. (2015). Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration. International Journal of Nanomedicine, 10, 6027–6037. https://doi.org/10.2147/IJN.S90347

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