Development of Lutein Based Liposomal Formulation for The Treatment of Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is a painless eye disorder in which the macula is damaged, causing visual loss. Pathophysiology starting with the oxidative stress which further leads to inflammation of macula and neovascularization. Oxidative stress, inflammation, neovascularization in the onset and progression of AMD. Carotenoids were studied as an essential dietary substance which reduces the risk of diseases and build up immune system. Lutein is a carotenoid of the xanthophyll class that is abundant in the fibrous layers of the fovea, where it forms the macular pigment. It functions as an antioxidant and protects the body from photooxidative damage. To macula making a potential candidate in reducing risk of AMD. The usage of lutein is restricted due to its low oral bioavailability, which is caused by its poor water solubility and stability. The research shown that for enhancement of bioavailability and stability liposomes are preferred carriers. Liposomes are non-toxic and biocompatible vesicular nanocarriers which can be used to encapsulate Lutein to enhance its solubility and deliver in a sustained manner with potential targeted delivery. The main purpose of thiswork was to develop and optimize systemically lutein loaded liposomal formulation for the treatment of AMD. In excipients selection L-alpha Phosphatidylcholine as Lipid, Cholesterol as Stabilizer and Phosphate buffer saline 7.4 pH as a solvent were selected. For the ocular drug delivery of lutein liposome ideal particle size was targeted as less than 200 nm. Thin film hydration and Ethanol injection were used for development of liposomes. From that ethanol injection method was chosen as it showed good results for achieving particle size less than 200nm. %Cholesterol to L-alpha phosphatidylcholine and % Drug to L-alpha phosphatidylcholine were selected as the critical parameters based on preliminary trails. The design of experiment (DOE) methodology was used for further optimization. For the evaluation of the design batches, hydrodynamic size, ZETA potential, PDI, and percent entrapment efficiency were employed as criteria for selecting the optimal batch. When compared to pure API, optimized formulations were further evaluated by DSC, SEM, TEM, and in-vitro drug diffusion. The optimized batch yielded hydrodynamic size around 120-130nm, zeta potential was found to be in the range of -15 to -23mV, PDI was less than 0.300 and % entrapment efficiency 45 to 55%. The in-vitro drug diffusion of formulation showed better drug release and solubility enhancement compared with the pure lutein API. These characterizations identify that Lutein liposomal formulation shows good hydrodynamic behavior, stability, and drug release compared to the conventional formulation.