Investigation of Galactosylated Low Molecular Weight Chitosan-Coated Liposomes for Cancer Specific Drug Delivery

摘要

Purpose: To assess the hepatocyte targeting potential of galactosylated low molecular weight chitosan (Gal-LMWCs)-coated liposomes bearing doxorubicin hydrochloride (DOX). Methods: Chitosan (CS) was depolymerized and lactobionic acid (LA) containing a galactose group was coupled with low molecular weight chitosan (LMWC) using carbodiimide chemistry. Two types of galactosylated polymers with variable degree of substitution were synthesized. Liposomes were prepared using film casting method, coated with the synthesized polymers and characterized for vesicle shape and size, polydispersity, zeta potential, drug entrapment, coating efficiency, in vitro drug release and cytotoxicity on human hepatoma cell line (HepG₂). Results: Coating efficiency was greater for the polymer with a lower degree of substitution. The liposomes formed were spherical in shape with a size range of 110 - 160 nm, drug entrapment of 92.14 - 96.37 % and zeta potential of 20.6 - 29.4 mV. Gal-LMWC(s)-coated liposomes exhibited a maximum of 65 % in vitro drug release in 24 h in a sustained fashion. The 50 % inhibitory concentration (IC₅₀) values for liposomal formulations and drug solution were 2.81 and 5.98 μg/ml, respectively. Conclusion: Gal-LMWC (s) coated liposomes containing DOX that demonstrate targetability to human hepatocellular carcinoma cell line ( in vitro ) have been successfully developed.