Low Molecular Weight Chitosan Coated Liposomes For Ocular Drug Delivery

In this study low molecular weight chitosan coated liposomes (Litosome, LCHL) through electrostatic force and hydrogen bond was proposed and investigated its in vitro and in vivo properties, Its potential use as a novel biocompatible and bioadhesive ocular drug carrier with penetration enhancement and prolonged retention was evaluated.Diclofenac Sodium (DS) and Cyclosporin A (CsA) were chosen as model molecule each for hydrophilic and lipophilic candidates.LCH with different molecular weight was prepared and used as a coating polymer on the surface of liposome loaded with diclofenac sodium. The coating process was accomplished spontaneously by the interactions between the polycationic polymer and the negatively charged lipids. TEM, SEM, DSC, particle size and zeta potential measurements were carried out. The effects of molecular weight and concentration of low molecular weight chitosan on the liposomal coating process were studied. The numeric relations between coating variables and coating efficiency were established using mathematical model.DS was encapsulated into the LCHL by an innovative dynamic remote loading method, and the encapsulating efficiency was nearly 100%.After coating, the membrane permeability of liposome was decreased and resulted in a prolonged drug release profile in vitro. In 4℃storage LCH coated liposome demonstrated an improved physicochemical stability in terms of particle size and encapsulating efficiency. In the corneal penetration study, the apparent permeability coefficient of the drug was significantly promoted after coating, indicating the potential corneal penetration enhancing effect of LCH coating.The ocular bioadhesion property was evaluated by rabbit in vivo precorneal retention, and LCH coated liposome achieved a significantly prolonged retention compared to non-coated liposome or drug solution, which is attributed to the electrostatic force and hydrogen bond effect. In the ocular tolerance study, no irritation or toxicity was caused by continual administration of LCH coated liposome in a total period of 7 d. In vivo evaluation in rabbit aqueous humor, cornea and conjunctiva was carried, and improved bioavailability and MRT were demonstrated.CsA-LCHL was prepared by ethanol injection plus homogenization method and was characterized in vitro.In vitro drug release of LCHL was investigated, and it showed a delayed release profile comparing with non-coated liposome. Cytotoxicity and cell internalization of FITC-BSA labeled LCHL in rabbit conjunctival epithelium cell line were studied. LCHL demonstrated a very low toxicity to the cells, and the cell uptaking of the fluorescent marker was significantly facilitated in the presence of LCHL. In vivo study in rabbits showed that the concentrations of CsA in cornea, conjunctiva, sclera and iris were remarkably increased by LCHL.LCHL could perform the drug delivery mechanism of both liposome and LCH, therefore brought biocompatibility, bioadhesion, penetration enhancement and prolonged retention in ocular drug delivery by synergistic reaction. In conclusion, LCHL might be a potential ocular drug carrier with highly valued socioeconomic potential.