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Liposomal formulations of poorly soluble camptothecin: drug retention and biodistribution

Permanent link
https://hdl.handle.net/10037/8984
DOI
https://doi.org/10.3109/08982104.2012.742537
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Accepted manuscript version (PDF)
Date
2012-12-05
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Flaten, Gøril Eide; Chang, Ting-Tung; Phillips, William T.; Brandl, Martin; Bao, Ande; Goins, Beth
Abstract
Context: Camptothecin (CPT) represents a potent anticancer drug. Its therapeutic use however is impaired by both drug solubility, hydrolysis and protein interactions in vivo. Use of liposomes as drug formulation approach could overcome some of these challenges.

Objective: The objective of this study was to perform a mechanistic study of the incorporation and retention of the lipophilic parent CPT-compound in different liposome formulations using radiolabeled CPT and thus be able to identify promising CPT delivery systems. In this context we also wanted to establish an appropriate mouse tumor model, in vivo scintigraphic imaging and biodistribution methodology for testing the most promising formulation.

Materials and methods: CPT retention in various liposome formulations following incubation in buffer and serum was determined. The HT-29 mouse tumor model, 111In-labeled liposomes as well as 3H-labeled CPT were used to investigate the biodistribution of liposomes and drug.

Results and discussion: The ability of different liposome formulations to retain CPT in buffer was influenced by the lipid concentration and the drug:lipid ratio rather than lipid composition. The tested formulations were cleared from the blood in the following order:CPT-solutionCPTliposomes 111In-labeled liposomes, and liposomes mainly accumulated in liver.

Conclusion: Lipid composition did not influence CPT retention to the same extent as earlier observed in incorporation studies. The set up for the biodistribution study works well and is suited for future in vivo studies on CPT liposomes. The biodistribution study showed that liposomes circulated longer than free drug, but premature release of drug from liposomes occurred. Further studies to develop formulations with higher retention potential and prolonged circulation are desired.

Description
Accepted manuscript version. Published version available at http://dx.doi.org/10.3109/08982104.2012.742537
Publisher
Taylor & Francis
Citation
Journal of liposome research 2013, 23(1):70-81
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