Modulation of Schlemm's canal endothelial cell stiffness via latrunculin loaded block copolymer micelles

Abstract Increased stiffness of Schlemm's canal endothelial cells (SC cells) is a major contributing factor to the increased pressure characteristic of primary open‐angle glaucoma. New treatments for glaucoma are being developed using actin depolymerizers and rho kinase inhibitors to address this increased stiffness. However, these agents have off‐target effects and are not as potent as had been hoped. We have developed a micellar nanocarrier assembled from poly(ethylene glycol)‐ bl ‐poly(propylene sulfide) copolymers capable of encapsulating latrunculin A (Lat A) with the goal of modulating SC cell stiffness. Lat A‐loaded nanocarriers were similar in size and morphology to unloaded poly (ethylene glycol)‐ bl ‐poly(propylene sulfide) (PEG‐ bl ‐PPS) micelles, loaded Lat A at 62% encapsulation efficiency, and retained loaded Lat A for at least 22 days. The continued functional activity of Lat A following encapsulation within micelles was verified in murine macrophages, which are known to display decreased endocytosis in response to Lat A‐dependent cytoskeletal disruption. Endocytic inhibition remained unchanged when comparing equal concentrations of micelle‐loaded versus free form Lat A. Uptake of Lat A‐loaded micelles by human SC cells was verified in vitro with no sign of cytotoxicity, and modulation of SC cell stiffness was measured by atomic force microscopy. Lat A‐loaded micelles significantly decreased SC cell stiffness, which resulted in visible changes in cell morphology as observed by confocal microscopy. Our results demonstrate that PEG‐ bl‐ PPS micelles represent a tunable platform for the controlled intracellular delivery of latrunculin. These self‐assembled polymeric nanobiomaterials may support the rational design and engineering of delivery systems for the treatment of glaucoma. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1771–1779, 2018.