Al-Atout, Rama – Mixed polymeric micelles based on hyaluronic acid-grafted PPG copolymer for ophthalmic delivery of dexamethasone (Dr. Heather Sheardown)

Topical drug delivery to the anterior segments of the eye, such as the iris and cornea, is limited and commonly ineffective. Conventional ophthalmic medications, such as eye drops, typically exhibit poor ocular bioavailability after administration due to the anatomical and physiological barriers of the eye. Additionally, eye drops have a short residence time in the anterior region, which results in frequent administration of drops to achieve the desired therapeutic effect. In this study, a novel polymeric mixed micelle system was developed to improve the residence time, enhance the ocular bioavailability, and allow for sustained release of dexamethasone (DEX) to treat anterior uveitis, which is an inflammation that effects the iris and ciliary body.

The mixed micelles were based off of hyaluronic acid (HA)-grafted-polypropylene glycol (PPG) copolymer (HA-g-PPG). Different amounts of either Pluronic F127 or D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) were added to the base copolymer to form mixed micelles, named HA-g-PPG/F127 and HA-g-PPG/TPGS micelles, respectively. The unloaded and DEX-loaded mixed micelles were prepared using a thin film hydration method, and their physicochemical properties were characterized and compared to HA-g-PPG single micelles.

The diameter of the HA-g-PPG/F127 mixed micelle formulation was 143.6 ± 5.618 nm, and 122.2 ± 7.032 nm for the HA-g-PPG/TPGS. The entrapment efficiency of DEX was 83% ± 6% for the HA-g-PPG/F127 system, and 84% ± 3% for HA-g-PPG/TPGS. The in vitro release studies showed that the HA-g-PPG/F127 and the HA-g-PPG/TPGS mixed micelles released 80% of DEX at 32 hours and 28 hours, respectively, compared to 14 hours for HA-g-PPG single micelles, and 5 hours for the DEX solution without micelles. These findings suggest that the HA-g-PPG/F127 and HA-g-PPG/TPGS mixed micelles could be used as nanocarriers for the sustainable delivery of DEX to treat anterior uveitis.