Designing biocompatible curcumin-loaded Pluronic F127 micelles for enhanced ocular drug delivery

Curcumin (CUR), a water-insoluble compound with antioxidant and anti-VEGF properties, faces challenges in application due to poor water solubility and fast degradation, limiting its bioavailability for ocular drug delivery (OcDD). This study aimed to enhance the aqueous solubility of CUR and the physical stability of the formulation by forming CUR-loaded Pluronic® F127 (PF127) micelles. The study revealed that PF127 formed micelles at a critical micelle concentration (CMC) of 0.21 ± 0.04% (w/v) in water. CUR-loaded PF127 micelles were prepared using three formulation methods and two centrifugation speeds to evaluate their influence on micelle sizes, redispersion, drug encapsulation efficiency (EE), and drug loading (DL). Among the tested formulations, CUR-loaded PF127 micelles prepared by thin-film hydration and centrifuged at 15000 rpm showed optimal particle sizes (∼20 nm) with %EE ranging from 4% to 72% depending on the drug to polymer ratio (1:10 to 1:120). These micelles remained physically stable after freeze-drying and sonication, with no significant size changes. Differential scanning calorimeter analysis revealed a shift in the thermogram and the presence of an amorphous phase, suggesting successful conversion of CUR from its crystalline form to an amorphous state within the micellar structure. Cytotoxicity studies demonstrated CUR-loaded micelles exhibited lower toxicity compared to free CUR at higher concentrations. In vitro drug release showed sustained CUR release (∼23%) over 7 days, and ex vivo drug permeation studies revealed higher CUR retention in both the cornea and sclera of porcine eyes with CUR-loaded PF127 micelles compared to the control group of free CUR after 6 h. The ex vivo tissue uptake study also indicated enhanced permeation of CUR when delivered via PF127 micelles, showing stronger fluorescence signals within the tissue compared to free CUR. Therefore, this study demonstrates an interesting proof of concept for developing CUR-loaded PF127 micelles as an innovative and effective strategy for treating eye diseases in OcDD application.