Sustained release of hydroxycamptothecin after subcutaneous administration using a novel phospholipid complex—DepoFoam™ technology

Abstract

Objective: In order to prolong the duration of drug in the circulation, multivesicular liposome (MVL, namely DepoFoam™) was utilized as a sustained-release delivery system for hydroxycamptothecin (HCPT). Methods: HCPT is insoluble in both water and physiological acceptable organic solvents; therefore, HCPT–phospholipid complex (HCPT–PCC) was prepared by solvent evaporation method to improve its liposolubility. In this study, preparation, characterization, in vitro release, and in vivo pharmacokinetics of HCPT–phospholipid complex-loaded MVLs (HCPT-MVLs) were investigated. Results: The results showed that the average particle size of HCPT-MVL was 9 μm and the encapsulation efficiency was 90%. In addition, HCPT-MVLs could improve both in vitro release and in vivo pharmacokinetic behaviors of the original drug, with a sustained release of drugs over 5–6 days. Conclusion: These data suggested that by combined use of DepoFoam™ and phospholipid complex formation technique HCPT could be successfully entrapped into the MVLs, which might provide a paradigm for sustained release of insoluble drugs.

Keywords:

• Hydroxycamptothecin
• multivesicular liposomes
• phospholipid complex
• sustained release

Acknowledgments

We are thankful for financial support from the National S & T Major Project of China (grant no.: 2009ZX09310–002) and the 973 program of Chinese government (no. 2007CB935801).

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.