| Title | Effect of altered temperature storage on the in vitro cellular uptake of liposome drug products. | | Author(s) | Volpe DA, Shaw AB, Chen XH, Zhou L, Chen ML | | Institution | Office of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA. | | Source | J Liposome Res 2009 Oct 22. | | Abstract | The aim of this study was to evaluate whether temperature stress conditions affect the cellular uptake of liposomal doxorubicin, Doxil((R)) (DXL; Ortho Biotech, Raritan, New Jersey, USA), and liposomal daunorubicin, DaunoXome((R)) (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 degrees C, as compared to storage in their buffered formulations at the labeled temperature of 4 degrees 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 degrees C. Exposure of DXL to 22 degrees C stress decreased its uptake by SKOV-3 cells, when compared to exposure of DXL to 4 degrees 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19848447 |
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