Background and Objective: Ocular drug delivery is one of the most interesting and challenging issues that pharmaceutical scientists encounter (1). Ocular bioavailability of topically administered drugs is less than 5% (2, 3). Micelles as nanoparticulate drug delivery systems have been studied for improving topical ocular delivery of hydrophobic drugs (4). In this contribution, our goal was to encapsulate
dexamethasone (DEX) as a model drug in polylatide-polycaprolactone-polyethylene glycol- polycaprolactone-polylatide (PLA-PCL-PEG-PCL-PLA)
micelles with sustained release properties to improve the ocular bioavailability of poorly water-soluble drugs.Materials and Methods: The PLA-PCL-PEG-PCL-PLA
copolymers were synthetized by a ring opening polymerization method using stannous octoacte (Sn(Oct) 2 ) as the catalyst. The resulting
copolymers were characterized with 1 H NMR, Fourier transform infrared, gel permeation chromatography, X-ray diffraction, and differential scanning calorimetry. Critical micelle concentration (CMC) of the
copolymers obtained was determined. DEX was loaded into the polymeric
micelles by single o/w emulsion solvent evaporation method, and the DEX-loaded
micelles were characterized with DLS and TEM. The release profile of DEX from the PLA-PCL-PEG-PCL-PLA
micelles was determined using the in vitro release study in simulated tear fluid (STF). The drug release kinetics and the membrane permeability were also determined.Findings: The pentablock
copolymers were successfully synthetized. The TEM results verified the formation of the spherical micelles. The size of the prepared
micelles was approximately 90 nm. The
micelles exhibited an initial burst release followed by a sustained release, which lasted for 48h. Among the kinetic models employed, the Weibull s distribution model exhibited the best fit compared to the other ones. The apparent permeability of the
micelles was higher compared to the marketed DEX drop.Conclusion: These results indicate that the PLA-PCL-PEG-PCL-PLA
micelles can be suitable candidates for ocular delivery of DEX and likely other hydrophobic drugs