Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma

Minyan Wei,1,2 Xiucai Guo,1,3 Liuxiao Tu,1 Qi Zou,1 Qi Li,1 Chenyi Tang,1 Bao Chen,1 Yuehong Xu,1 Chuanbin Wu1 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Guangzhou Medical University, 3Department of Pharmacy, 12th People’s Hospital of Guangzhou City, Guangzhou, People’s Republic of China Abstract: Lactoferrin (Lf) is a potential-targeting ligand for hepatocellular carcinoma (HCC) cells because of its specific binding with asialoglycoprotein receptor (ASGPR). In this present work, a doxorubicin (DOX)-loaded, Lf-modified, polyethylene glycol (PEG)ylated liposome (Lf-PLS) system was developed, and its targeting effect and antitumor efficacy to HCC was also explored. The DOX-loaded Lf-PLS system had spherical or oval vesicles, with mean particle size approximately 100 nm, and had an encapsulation efficiency of 97%. The confocal microscopy and flow cytometry indicated that the cellular uptake of Lf-PLS was significantly higher than that of PEGylated liposome (PLS) in ASGPR-positive cells (P0.05). Cytotoxicity assay by MTT demonstrated that DOX-loaded Lf-PLS showed significantly stronger antiproliferative effects on ASGPR-positive HCC cells than did PLS without the Lf modification (P