Preparation and In Vitro Evaluation of Thermosensitive Liposomes Targeting Ovarian Cancer

Abstract

Introduction: Liposomes have been widely used in drug delivery systems because the encapsulation of liposomes changes the biological distribution profile and improves the therapeutic indices of various drugs. Thermosensitive liposomes have been proven to be a precise and effective method for cancer therapy in many preclinical studies. However, the lack of specific targeting ability to cancer cells limited their application in safe and efficient chemotherapy.

Methods: In the present study, an ovarian targeting ligand namely WSGFPGVWGASVK (WSG) screened by phage display in vivo was grafted on the thermosensitive phospholipids to prepare the liposomes targeting ovarian cancer cells. WSG was first grafted onto the hydrophilic terminal of DSPEPEG2000 molecules, and then the WSG modified thermosensitive liposomes (WSG-Lipo) were prepared by thin-film hydration method. Doxorubicin hydrochloride (DOX) was used as a model drug to investigate the drug release behavior of liposomes at different temperatures. The specificity of liposomes to SKOV-3 cells was studied by cell uptake in vitro.

Results: The WSG-Lipo-DOX could release more DOX at 42°C than at 37°C, showing stronger specificity to SKOV-3 cells and thus selectively inhibiting SKOV-3 cells activity in vitro.

Conclusion: The active targeting liposome showed potential in improving the specificity of thermosensitive liposomes and would be applied in the chemotherapy combined with a thermotherapy.

Keywords: Thermosensitivity; cellular specificity; controlled drug release; liposomes; ovarian cancer; tumor targeting.