Self-assembled liquid crystalline nanoparticles as a novel ophthalmic delivery system for dexamethasone: Improving preocular retention and ocular bioavailability

The object of this study was to design novel self-assembled liquid crystalline nanoparticles (cubosomes) as an ophthalmic delivery system for dexamethasone (DEX) to improve its preocular retention and ocular bioavailability DEX cubosome particles were produced by fragmenting a cubic crystalline phase of monoolein and water in the presence of stabilizer Poloxamer 407. Small angle X-ray diffraction (SAXR) profiles revealed its internal structure as Pn3m space group, indicating the diamond cubic phase. In vitro, the apparent permeability coefficient of DEX administered in cubosomes exhibited a 4.5-fold (F1) and 3 5-fold (F2) increase compared to that of Dex-Na phosphate eye drops Preocular retention studies revealed that the retention of cubosomes was significantly longer than that of solution and carbopol gel, with AUC(0 -> 180min) of Rh B cubosomes being 2-3-fold higher than that of the other two formulations In vivo pharmacokinetics in aqueous humor was evaluated by microdialysis, which indicated a 1 8-fold (F1) increase in AUC(0 -> 240min) of DEX administered in cubosomes relative to that of Dex-Na phosphate eye drops, with about an 8-fold increase compared to that of DEX suspension Corneal cross-sections after incubation with DEX cubosomes demonstrated an unaffected corneal structure and tissue integrity, which indicated the good biocompatibility of DEX cubosomes In conclusion, self-assembled liquid crystalline nanoparticles might represent a promising vehicle for effective ocular drug delivery Crown Copyright (C) 2010 Published by Elsevier B V. All rights reserved