Poloxamine micellar solubilization of α-tocopherol for topical ocular treatment

Ophthalmic delivery of α-tocopherol (TOC), which is the most active and cost/effective form of vitamin E, is receiving increasing attention as a way of preventing and treating glaucoma, cataracts, and dry eye syndrome, among other ocular pathologies. The aim of this work was to elucidate the possibility of using poly(propylene oxide) (PPO) and poly(ethylene oxide) (PEO) block copolymers of poloxamine family (namely, Tetronic 1107) to develop polymeric micelles that can host TOC, enhance the apparent solubility and sustain the release of this vitamin in lachrymal fluid. The interactions of Tetronic 1107 with TOC were analyzed at the air-water interface recording the π-A isotherms at various temperatures, indicating favorable interactions as temperature increased from 10 to 29 °C. In 0.9% NaCl aqueous medium, a sharp increase in TOC solubility was observed when T1107 surpasses the critical micellar concentration (CMC); the apparent solubility in 20% T1107 being more than 600-fold and 6000-fold that observed in the absence of copolymer at 4 and 25 °C, respectively. Micelles were characterized before and after loading by means of dynamic light scattering (DLS) and transmission electronic microscopy (TEM). TOC sustained release profiles were recorded in Franz-Chien diffusion cells. After storage for 3 months at 4 °C, TOC-loaded T1107 10% micellar system retained 84% TOC solubilized, which maintained the antioxidant activity. Furthermore, the rheological properties of the micellar systems were not altered either; the viscoelastic parameters being dependent on T1107 concentration, which opens the possibility of developing from free-flowing eye-drops to in situ gelling systems.