Preparation and characterisation of the colistin-entrapped liposome driven by electrostatic interaction for intravenous administration

Abstract

Potential use of liposome for polycationic colistin is hindered by their phospholipid membrane permeability. In this study, liposomes were modified with sodium cholesteryl sulphate (Chol-SO₄⁻) for improving the colistin loading by enhancing the colistin-bilayer electrostatic attraction. We have evaluated two liposomes: colistin-entrapped liposome of Chol-SO₄⁻ (CCL) and coated Chol-SO₄⁻/colistin complex liposome (CCCL). In comparison with CCL which formed large aggregates at Chol-SO₄⁻/colistin charge ratio below 2:1, CCCL showed a smaller size less dependent on the charge ratio, probably arising from more colistin entrapped on the inner leaflet of bilayer. Both liposomes exhibited significantly increased entrapment efficiency as compared with the liposome without Chol-SO4⁻. But colistin released upon dilution, implying free transfer of colistin through bilayers. Pharmacokinetics results showed the approximately four-fold increase in the plasma AUC_0–8 h for CCCL and CCL as compared with colistin solution, showing potential benefit for infectious target localisation by prolonging the systemic circulation of colistin.

Keywords:

• Liposome
• electrostatic interaction
• colistin
• pharmacokinetics
• sodium cholesteryl sulphate

Acknowledgements

The authors are grateful to the Electron Microscopy Service from Shenyang University of Technology for providing the TEM equipment.

Disclosure statement

The authors report that they have no conflicts of interests. This work was supported by the Project of Innovation Team of University from the Education Department of Liaoning, China (LT201023) and the Programme of Personnel Training from the National Basic Science Foundation, China (J1103606).