Preparation of bromfenac-loaded liposomes modified with chitosan for ophthalmic drug delivery and evaluation of physicochemical properties and drug release profile

Abstract

The purpose of this study was to design a submicron-sized liposomal non-steroidal anti-inflammatory drug (NSAID) preparation that targets the retina via topical instillation of eye drops. Bromfenac (BRF)-loaded liposomes were prepared using the calcium acetate gradient method. Liposome sizes and encapsulation efficiencies were optimized by screening several liposome formulations of lipid, drug concentration, and buffer solution. BRF entrapment efficiency was greater than 90% using this method, and was low using conventional hydration methods. High initial BRF loading using the pH gradient method caused aggregation of liposomes. To circumvent aggregation, the negatively charged lipid dicetylphosphate was incorporated into liposomes, which formed anion layer preventing coalescence. Release of BRF from liposomes was sustained for several hours depending on lipid concentration, inner water phase, initial drug amounts, and surface properties. Surface modification with chitosan (CS), a mucoadhesive cationic polymer, was achieved using electrostatic interactions of negatively charged liposomes. The optimal concentration of CS for evasion of liposome aggregation was 0.15%.