Purpose: Topical corticosteroids administration is commonly used for management of various ocular conditions especially those affecting the anterior segment of the eye. Poor solubility and limited pre-corneal residence time result in insufficient drug penetration to the outer (cornea and conjunctival-scleral) coats of the eye. This study aimed to prepare and evaluate cubosomes for prolonging residence time and enhancing ocular bioavailability of BDP.
Methods: GMO-cubosomes were prepared using the top-down technique. Two stabilizers were investigated: poloxamer 407 and solulan C24. Particle size, EE %, polarized-light microscopy, TEM, in vitro release, transcorneal permeation, BCOP, histopathology and in vivo evaluation for treatment of uveitis in a rabbits' model were studied.
Results: The prepared cubosomes were of nano-sizes (100 nm - 278 nm); EE% was around 94%. The cubosomes were confirmed by visualizing the "Maltese crosses" textures. Transcorneal permeation was significantly (p < 0.05) improved, compared to BDP-suspension (the control formulation). The optimized cubosomes F1P was incorporated in CMC gel (Cubo-gel). The prepared Cubo-gel formulations showed better rheological characteristics and high ocular tolerability. Superior anti-inflammatory properties were recorded for the Cubo-gel for treatment of endotoxin-induced uveitis in the rabbit model when compared to the control BDP-suspension.
Conclusions: Transcorneal permeation parameters Papp and flux and AUC0-10h markedly enhanced by up to 4-, 5.8-and 5.5-fold respectively, compared to the control BDP-suspension formulation. This study suggested that cubosomes/Cubo-gel could be an auspicious ocular delivery system for BDP that was able to effectively treat uveitis (a disease of the posterior segment of the eye).
Keywords: BCOP assay; Cubosomes; beclomethasone dipropionate; ocular drug delivery; residence time; uveitis.