Preparation and evaluation of PCL-PEG-PCL micelles as potential nanocarriers for ocular delivery of dexamethasone

Objective(s): Micelles have been studied as nanoparticulate drug delivery systems for improving the topical ocular delivery of hydrophobic drugs. The objective of this study was to develop and characterize dexamethasone-loaded polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) micelles to improve patient compliance and enhance the ocular bioavailability of poorly water-soluble drugs. Materials and Methods: The PCL-PEG-PCL copolymers were synthesized via the ring opening polymerization of ε-caprolactone in the presence of PEG. The resulting purified copolymers were characterized by GPC, NMR, FTIR, XRD and DSC. The critical micelle concentrations (CMCs) of the copolymers mentioned were determined. Dexamethasone was loaded into polymeric micelles by film hydration method, and dexamethasone-loaded micelles were characterized by TEM and DLS. Drug release kinetics and ex vivo corneal permeability were also determined. Results: The CMC of the synthetized copolymers was approximately 0.03 mg/ml. Aqueous solutions of the resulting copolymers (400 mg/ml) rapidly formed a gel in situ at 34 °C. The TEM results exhibited the successful formation of spherical micelles. The size of the prepared micelles was approximately 40 nm. Formulated micelles sustained the release of the incorporated dexamethasone for 5 days. Conclusion: Data from ex vivo permeability tests indicated that PCL-PEG-PCL micelles can be suitable candidates for the ocular delivery of dexamethasone and, likely, other hydrophobic drugs.