Preparation, Characterization, and in vivo Pharmacokinetics of Innovative Mixed Polymeric Nanomicelles Coated with Hyaluronic Acid as a Retinal Brimonidine-Carrier System

Background: Due to the limited ocular bioavailability, local ocular injections and systemic delivery were used instead of topical application. These alternative approaches were accompanied by numerous disadvantages. Objectives: Create and test mixed polymeric nanomicelles coated with hyaluronic acid as a topical drug carrier for targeted delivery to the vitreous fluid and retina, overcoming the limitations of eye drops. Methods: The thin-film hydration process was utilized to create nanomicelles, and their physical properties were studied. Colored, pigmented, healthy albino rabbits were employed in vivo experiment. Following anesthesia, 35µl of brimonidine nanomicelles and Alphagan® were administered topically. Samples from the vitreous and retina were collected for RP-HPLC analysis. Results: The nanomicelles' physical qualities made them appropriate as a carrier system for the vitreous fluid. They were spherical with a clear appearance and a pharmacological concentration of 97.11%. The particle size range was 134.2nm, with a PDI of 0.2824. The drug entrapment effectiveness was 62.69%, whereas the surface tension was 39.18 mN/m. Their vitreous pharmacokinetics Cmax, Tmax, and AUC0-t were 28.1ng/µl, 2.0min, and 1268.6ng/µl*min, respectively, compared to 5.0ng/µl, 8.0min, and 129.32ng/µl*min for Alphagan eye drops. The retinal pharmacokinetics were 64.9ng/µl, 17.0min, and 18688.04ng/µl*min, respectively, compared to 31.6ng/µl, 30min, and 6377.67ng/µl*min with Alphagan eye drops. Conclusions: Brimonidine nanomicelles coated with hyaluronic acid could be an effective topical drug-carrier method for delivering medications to the vitreous and retina, with higher bioavailability than eye drops.