International Journal of Nanomedicine (Jun 2016)
Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine
Abstract
Hamdy Abdelkader,1,2 Michael R Longman,1 Raid G Alany,1,3 Barbara Pierscionek4 1Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, London, UK; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Mina, Egypt; 3School of Pharmacy, The University of Auckland, Auckland, New Zealand; 4Vision Cognition and Neuroscience Theme, Faculty of Science, Engineering and Computing, Kingston University London, Kingston Upon Thames, London, UK Abstract: This study reports on L-carnosine phytosomes as an alternative for the prodrug N-acetyl-L-carnosine as a novel delivery system to the lens. L-carnosine was loaded into lipid-based phytosomes and hyaluronic acid (HA)-dispersed phytosomes. L-carnosine-phospholipid complexes (PC) of different molar ratios, 1:1 and 1:2, were prepared by the solvent evaporation method. These complexes were characterized with thermal and spectral analyses. PC were dispersed in either phosphate buffered saline pH 7.4 or HA (0.1% w/v) in phosphate buffered saline to form phytosomes PC1:1, PC1:2, and PC1:2 HA, respectively. These phytosomal formulations were studied for size, zeta potential, morphology, contact angle, spreading coefficient, viscosity, ex vivo transcorneal permeation, and cytotoxicity using primary human corneal cells. L-carnosine-phospholipid formed a complex at a 1:2 molar ratio and phytosomes were in the size range of 380–450 nm, polydispersity index of 0.12–0.2. The viscosity of PC1:2 HA increased by 2.4 to 5-fold compared with HA solution and PC 1:2, respectively; significantly lower surface tension, contact angle, and greater spreading ability for phytosomes were also recorded. Ex vivo transcorneal permeation parameters showed significantly controlled corneal permeation of L-carnosine with the novel carrier systems without any significant impact on primary human corneal cell viability. Ex vivo porcine lenses incubated in high sugar media without and with L-carnosine showed concentration-dependent marked inhibition of lens brunescence indicative of the potential for delaying changes that underlie cataractogenesis that may be linked to diabetic processes. Keywords: lipoid S 75, phytosomes, L-carnosine, cataract, hyaluronate sodium, ocular delivery
