High-Capacity Dexamethasone-Loaded Poly(2-Oxazoline) Micelles for Ocular Surface Applications

The clinical efficacy of dexamethasone (DEX) in ocular therapy remains limited by its low aqueous solubility and restricted epithelial permeability. To address these limitations, we developed high-capacity micellar formulations by a modified thin-film hydration method utilizing two poly(2-oxazoline) (POx)-based ABA triblock copolymers (A-pBuOx-A and A-pPentOx-A). We achieved drug loading capacities of up to 33 wt.%. The DEX loaded nanoformulations were characterized by differential scanning calorimetry and powder X-ray diffraction confirming the amorphous nature of DEX in lyophilized formulations. The micelles had a hydrodynamic diameter of Dh ≈ 18-24 nm. Both polymers were well tolerated and did not show any toxicity in primary human conjunctival fibroblasts and epithelial cells up to 50 g/L. Furthermore, the A-pBuOx-A/DEX formulation increased the apparent permeability of DEX approximately 12.2-fold across a primary human conjunctival epithelial barrier compared with Dexa EDO, without evidence of compromised barrier integrity or cell viability. These findings establish the POx polymer platform as a promising approach for enhancing epithelial delivery of poorly water-soluble ophthalmic drugs.