title: Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine.
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.
authors.affiliation: Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, London, UK; Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Mina, Egypt.
authors.forename: Hamdy
authors.initials: H
authors.lastname: Abdelkader
authors.affiliation: Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, London, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Longman
authors.affiliation: Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, London, UK; School of Pharmacy, The University of Auckland, Auckland, New Zealand.
authors.forename: Raid G
authors.initials: RG
authors.lastname: Alany
authors.affiliation: Vision Cognition and Neuroscience Theme, Faculty of Science, Engineering and Computing, Kingston University London, Kingston Upon Thames, London, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pierscionek
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002241:Carbohydrates / Q000494:pharmacology; D002336:Carnosine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D005123:Eye / Q000187:drug effects*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007908:Lens, Crystalline / Q000187:drug effects; D008081:Liposomes; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013500:Surface Tension / Q000187:drug effects; D034421:Sus scrofa; D014783:Viscosity / Q000187:drug effects; D014961:X-Ray Diffraction
chemical_list: D002241:Carbohydrates; D008081:Liposomes; D012997:Solvents; D002336:Carnosine; D006820:Hyaluronic Acid
keywords: L-carnosine; cataract; hyaluronate sodium; lipoid S 75; ocular delivery; phytosomes