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

Abstract

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.

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies

“…From the posterior segment, the polymeric micelles may be further engulfed by RPE cells by endocytosis to generate therapeutic concentrations in posterior ocular tissues [40–42]. Such tissue absorption and cellular uptake depend on the surface charge and size of the micelles [43]. Fig.…”

“…A time-dependent corneal stroma localization was obtained indicating the potential of polymeric micelles to overcome the epithelial barrier and release the incorporated drug into the stroma. Furthermore, PEGylated shells of these polymeric micelles exhibited higher stability and improved the solubility in both hydrophilic and hydrophobic drugs leading to their effective penetration into the amphipathic cornea [43]. In another study, Meyer et al investigated indocyanine green/2-hydroxyethyl 12-hydroxyoctadecanoate (ICG/Kolliphor HS15) micellar formulations in an animal model of laser-induced choroidal neovascularization.…”

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

“…32 Briefly, 2 mL each of the (±) L/NP formulations was separately loaded into dialysis bags immersed in 40 mL freshly prepared Ringer's solution at 34°C. The magnetic stirring speed was 100 rpm.…”

Celastrol nanomicelles attenuate cytokine secretion in macrophages and inhibit macrophage-induced corneal neovascularization in rats

“…17,18 Furthermore, the developed CNMs could enhance the apparent aqueous solubility and improve the kinetic and thermodynamic stability in aqueous solution, compared with other carrier materials. 19 Moreover, the appropriate diameter (48 nm) and excellent amphipathic solubility of PEG-containing micelles might make it easy to penetrate the ocular barrier. 19 Therefore, polymeric nanomicelles might be better chosen as the celastrol delivery vector to further study the efficacy of CNMs in the treatment of ocular diseases.…”

“…19 Moreover, the appropriate diameter (48 nm) and excellent amphipathic solubility of PEG-containing micelles might make it easy to penetrate the ocular barrier. 19 Therefore, polymeric nanomicelles might be better chosen as the celastrol delivery vector to further study the efficacy of CNMs in the treatment of ocular diseases.…”