Effects of surface charge of low molecular weight heparin-modified cationic liposomes on drug efficacy and toxicity

Abstract

Cationic liposome is a potential nanocarrier to deliver drugs to solid tumor with proven efficiency in targeting tumor tissues. However, the major limitation is their charge-related instability and blood toxicity via intravenous injection. In order to overcome these problems and to maintain tumor targeting potency, we modified the cationic liposomes with low molecular weight heparin (LMWH) to obtain series of liposomes with different surface charges. Both in vitro and in vivo studies including serum stability, blood hemolysis, cellular uptake, cytotoxicity and in vivo biodistribution were evaluated. The results indicated the cationic liposome with surface charge of 5 mV (denoted as LLip-C) had the similar stability in serum and mild hemocytolysis compared with that of anionic liposome (LLip-D), but better cellular uptake owing to electrostatic interaction between cationic liposomes and cell membranes. Furthermore, we prepared curcumin-loaded liposomes to investigate the therapy efficiency. The intracellular distribution of curcumin-loaded LLip-C (Curcumin-LLip-C) was inclined to locate in cytoplasm and nuclei than curcumin-loaded LLip-D (Curcumin-LLip-D). In vitro cytotoxicity of Curcumin-LLip-C also exhibited higher inhibition of tumor cells than that of Curcumin-LLip-D. These results certified that a slightly positive surface charge of nanocarriers could achieve the balance between well antitumor efficiency and mild adverse effects.

Keywords:

• Cationic liposome
• low molecular weight heparin
• surface charge
• blood toxicity
• tumor targeting

Disclosure statement

The authors report no conflicts of interest of any nature in this work.

Additional information

Funding

This work was financial supported by National Natural Science Foundation of China (grant No. 81603048), Natural Science Foundation of Jiangsu Province (grant No. BK20160752), Fundamental Research Funds for the Central Universities (grant No. 2016ZPY014) and program of the "333 high-level personnel training project (No. BRA2015392)" young leaders in science and technology of Jiangsu Province and Public Technology Service Center of Nano drug Preparation and Evaluation of Jiangsu Province.