Effect of altered temperature storage on the in vitro cellular uptake of liposome drug products

Abstract

The aim of this study was to evaluate whether temperature stress conditions affect the cellular uptake of liposomal doxorubicin, Doxil^® (DXL; Ortho Biotech, Raritan, New Jersey, USA), and liposomal daunorubicin, DaunoXome^® (DXM; Gilead Sciences, San Dimas, California, USA). Uptake of these cytotoxic compounds is essential for their pharmacological effect. Commercially available DXL and DXM were stressed for 6 days under altered temperature conditions of 22 and 50°C, as compared to storage in their buffered formulations at the labeled temperature of 4°C. The cellular uptake of the liposomal drugs was measured by fluorescence intensity in human ovarian SKOV-3 and murine macrophage J774A.1 cell lines following a 4-hour exposure to DXL or DXM. There was a 5- to 10-fold increase in the cellular uptake of DXL and DXM in both cell lines after stress exposure to 50°C. Exposure of DXL to 22°C stress decreased its uptake by SKOV-3 cells, when compared to exposure of DXL to 4°C control conditions. A cell-based uptake assay may provide a means to assess changes in the functional activity of liposomes in conjunction with evaluation of their physicochemical properties in order to evaluate the stability and integrity of liposomes.

Keywords::

• Liposomes
• uptake
• stress
• temperature

Acknowledgements

The authors wish to thank Sylvia Colson and William Doub for their technical assistance during this study. The opinions expressed in this article are those of the authors and do not necessarily represent the views or policies of the FDA.

Declaration of interest: The authors declare no conflict of interest.