Evaluating in-depth potential of Pluronic F127-tailored complex micellar systems of etodolac for the therapeutic management of uveitis: A comprehensive preclinical study.

Intraocular inflammation, commonly referred as uveitis, results from various viral and non-infectious agents. Corticosteroids remain the primary treatment option for such diseased conditions, though their long-term usage is not recommended owing to potential several adverse effects, including ocular hypertension and glaucoma. Of late, NSAIDs have become popular drugs of choice for treating uveitis. Etodolac is one of such potent NSAIDs, which has not yet been much explored in therapeutic treatment of uveitis. The current work, therefore, aims to formulate etodolac-loaded complex micellar systems, which consist of Pluronic F-127, coupled with phospholipid and a cosolvent blend for uveitis management. The micellar systems exhibited spherical shape and nanometric size (i.e., 75.20 ± 8.60 nm) with low PDI (0.263), high zeta potential (-23.10 ± 6.12 mV), osmolarity of 295 ± 10 mOsmol/L, and drug encapsulation of 87.29 ± 7.41 %. Ex vivo transcorneal permeation experiments on freshly excised goat eyeballs, demonstrated substantially higher drug penetration (i.e., 66.74 ± 3.10 %) from complex micelles (CMs) vis-à-vis etodolac suspension (i.e., 23.00 ± 2.60 %, p < 0.001). The cytokine assays, viz. TNF-α and IL-6, corroborated distinctly higher anti-inflammatory potential of the formulation than drug solution (p < 0.01). In vivo LPS-induced uveitis model in rat too indicated 1.40-folds superior effectiveness of the CMs to commercial formulation (p < 0.01). The HCF cell line studies and ocular compliance experiments using HET-CAM test construed the biocompatible nature of the CMs. The studies, overall, explicitly testify the therapeutic promise of CMs-based etodolac formulation in treating ocular inflammatory disorders like uveitis.