Loteprednol etabonate loaded lyotropic liquid crystalline nanoparticles in-situ ophthalmic gel: Qbd driven optimization and in-vitro, ex-vivo evidence of sustained precorneal residence time

Ophthalmic treatment is challenging due to the numerous physiological barriers present in the eye. Loteprednol Etabonate (LE) is a corticosteroid used to treat ophthalmic inflammation. LE is currently available in the form of ointment, gel, and suspension drops. In this study, LE lyotropic liquid crystalline nanoparticles (LCNP) in-situ ophthalmic gel was formulated to get over the drawbacks of conventional drug delivery systems like low penetration, retention, and bioavailability of the drug through the cornea's surface. The objective of the proposed study was to develop LE-LCNP using a three-factor, five-level Central Composite Design of Response Surface Methodology. The optimized batch of LE-LCNP exhibited a particle size of 102.5 +/- 10.19 nm, PDI of 0.319 +/- 0.120, and entrapment efficiency of 57.32 +/- 3.44%. The in-vitro results revealed 99.99% drug release from LE-LCNP in 18 h. Further, the optimized LE-loaded LCNP formulation was incorporated into in-situ gelling systems to formulate and characterize a temperature-sensitive and ion-activated in-situ ophthalmic gel using Poloxamer 407 (P407) and Gellan gum (GG). The rheological study showed that the viscosity of LE-LCNP P407 and LE-LCNP GG in-situ ophthalmic gel formulation was 4.7 and 3.9-fold higher than marketed LE suspension, respectively, at 25 degrees C. The higher viscous characteristics of the LE-loaded LCNP in-situ ophthalmic gel led to improved ocular retention, efficacy, and patient compliance. The ex-vivo corneal permeation study of LE-LCNP P407 and LE-LCNP GG in-situ ophthalmic gel showed 7 and 2.5-fold higher ocular permeation when compared with the marketed LE suspension, respectively. The results suggested that LE-loaded LCNP in-situ ophthalmic gel has the potential to become an effective carrier system for the treatment of inflammatory disorders of the eyes.