PEGylated hyaluronic acid-coated liposome for enhanced in vivo efficacy of sorafenib via active tumor cell targeting and prolonged systemic exposure

• Published in: Nanomedicine 2018-02, Vol.14 (2), p.557-567
• Main Authors: Mo, Lingxuan, Song, Jae Geun, Lee, Hankyu, Zhao, Mengjia, Kim, Hyeon Young, Lee, Yoon Ji, Ko, Hyuk Wan, Han, Hyo-Kyung
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Survival; Drug Carriers - chemistry; Drug Delivery Systems; Female; Hemolysis - drug effects; Humans; Hyaluronic acid; Hyaluronic Acid - chemistry; Liposome; Liposomes - chemistry; Mice; Polyethylene Glycols - chemistry; Prolonged circulation; Rats; Rats, Sprague-Dawley; Sorafenib; Sorafenib - administration & dosage; Sorafenib - chemistry; Sorafenib - pharmacology; Tumor Cells, Cultured; Tumor targeting; Xenograft Model Antitumor Assays
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2017.12.003

This study aimed to design an effective formulation for enhancing the tumor-targeted delivery of sorafenib. Three sorafenib-loaded liposomal formulations including uncoated liposome (SF-Lip), hyaluronic acid-coated liposome (HA-SF-Lip), and PEGylated hyaluronic acid-coated liposome (PEG-HA-SF-Lip) were developed with narrow size distribution and high encapsulation efficiency. The cellular uptake and cytotoxicity of HA-SF-Lip and PEG-HA-SF-Lip were greater than those of SF-Lip in MDA-MB-231 cells overexpressing CD44, whereas there were no significant differences in MCF-7 cells with low CD44 expression, indicating the CD44-mediated cellular uptake of coated liposomes. In comparison with sorafenib solution, PEG-HA-SF-Lip increased the systemic exposure and plasma half-life in rats by 3-fold and 2-fold, respectively. Consistently, PEG-HA-SF-Lip was the most effective for tumor growth inhibition through CD44 targeting in the MDA-MB-231 tumor xenograft mouse model. Taken together, the present study suggests that PEG-HA-SF-Lip might be effective for the tumor-targeted delivery of sorafenib with enhanced systemic exposure and longer blood circulation. PEG-HA-SF-Lip was developed with narrow size distribution and high encapsulation efficiency. It exhibited higher cellular uptake in MDA-MB-231 cells overexpressing CD44 and consequently higher cytotoxicity. Furthermore, it achieved higher systemic exposure and longer blood circulating time after intravenous administration. Consistently, PEG-HA-SF-Lip increased the effectiveness of the tumor-targeted delivery of sorafenib and enhanced anticancer activity in tumor-bearing mice. [Display omitted]