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RESEARCH PAPER

Preparation and Evaluation of Cubosomes/Cubosomal Gels for Ocular Delivery of Beclomethasone Dipropionate for Management of Uveitis Sherif A. Gaballa 1 & Omar H. El Garhy 1 & Hossam Moharram 2 & Hamdy Abdelkader 1,3

Received: 5 April 2020 / Accepted: 10 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

ABSTRACT 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 conjunctivalscleral) 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 topdown 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 BDPsuspension. * Hamdy Abdelkader [email protected] 1

Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt

2

Department of Ophthalmology, Faculty of Medicine, Minia University, Minia, Egypt

3

Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, Minia, New Minia City, Egypt

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 BDPsuspension 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 . beclomethasone dipropionate . Cubosomes . ocular drug delivery . residence time . uveitis

ABBREVIATIONS AUC BCOP BDP CMC EE% GMO Papp TEM

Area under the curve Bovine corneal opacity and permeability assay Beclomethasone dipropionate Carboxymethylcellulose Entrapment efficiency percentage Glyceryl monooleate Apparent permeability coefficient Transmission electron microscopy

INTRODUCTION Corticosteroids are widely used in the treatment of numerous ophthalmic diseases including those affecting the anterior and posterior segments of the eye. Topical, systemic, and intraocu