The studies of N-Octyl-N-Arginine-Chitosan coated liposome as an oral delivery system of Cyclosporine A

Abstract

OBJECTIVES: An amphiphilic polymer N-Octyl-N-Arginine-Chitosan (OACS) was synthesized to coat the Cyclosporine A (CsA) liposomes (CL) to decrease the destruction of liposomes in gastrointestinal tract (GI) tract and improve its oral absorption. METHODS: CL and OACS-CsA liposomes (OACS-CL) were prepared by rotary-film evaporation method, and characterized by dynamic light scattering, transmission electron microscopy, atomic force microscope and releasing properties. In-situ single pass perfusion experiment and in-vivo studies in rats were carried out to verify its absorption enhancement. KEY FINDINGS: The characterization results showed that its particle size, zeta potential and morphology changed before and after polymer coating. Release experiment indicated that OACS could slow down drug release and protect its degradation in the stomach. In-situ single pass perfusion proved that the absorption of OACS-CL at the jejunum was enhanced about 3 and 22 times compared with commercial preparation of microemulsions (Tianke) and CsA suspensions, respectively. In vivo, AUC0→∞ of three different OACS-CL groups (93.48 ± 2.54, 100.98 ± 13.08 and 99.01 ± 19.02 h·μg/ml, respectively) were higher than those of Tianke (69.34 ± 7.93 h·μg/ml), CL group (54.31 ± 6.70 h·μg/ml) and suspensions (31.14 ± 1.30 h·μg/ml). CONCLUSIONS: Therefore, OACS coated liposomes can be an effective strategy to promote drug's absorption and further reduce the anaphylactic reaction of abundant surfactants in commercial preparations.