Liposomal drug delivery in multimodal cancer therapy
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AbstractEncapsulating cytostatics into lipid vesicles, i.e. liposomes, improves tumour drug accumulation and reduce adverse effects. Liposomal doxorubicin (DXR) has been used in the treatment of a variety of cancers and may also be suitable for combining with other treatment modalities. By modulating liposomal membranes, liposomes can be made ultrasound (US) sensitive releasing encapsulated drug in tumour tissue upon external US stimulation and may thereby improve therapeutic outcome. Moreover, as DXR is a potent radiosensitizer, liposomal DXR could enhance the effect of radiotherapy (RT) primarily in tumour tissue. This thesis evaluates multimodal cancer therapy combining liposomal DXR with US and RT in tumour-bearing mice. Also, the feasibility of using in vivo fluorescence optical imaging (OI) to study liposome tumour uptake was evaluated. Enhanced therapeutic effect of liposomal DXR was observed when combined with US applied to tumour. Liposomal DXR also improved therapeutic outcome of RT under radioresistant hypoxic conditions. The role of OI in quantitative assessment of liposome tumour uptake remains unresolved.
List of papers
|Paper I: Eirik Hagtvet, Tove J. Evjen, Dag Rune Olsen, Sigrid L. Fossheim, Esben A. Nilssen. Ultrasound enhanced antitumour activity of liposomal doxorubicin in mice. Journal of Drug Targeting, 2011:19(8):701-708. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.3109/1061186X.2010.551401|
|Paper II: Tove J. Evjen, Eirik Hagtvet, Esben A. Nilssen, Martin Brandl, Sigrid L. Fossheim. Sonosensitive dioleoylphosphatidylethanolamine-containing liposomes with prolonged blood circulation time of doxorubicin. European Journal of Pharmaceutical Sciences, 2011:43(4):318-324. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1016/j.ejps.2011.05.007|
|Paper III: Eirik Hagtvet, Tove J. Evjen, Esben A. Nilssen, Dag Rune Olsen. Assessment of liposome biodistribution by non-invasive optical imaging: A feasibility study in tumour-bearing mice. Journal of Nanoscience and Nanotechnology, 2012 Mar;12(3):2912-8. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1166/jnn.2012.5852|
|Paper IV: Eirik Hagtvet, Kathrine Røe, Dag Rune Olsen. Liposomal doxorubicin improves radiotherapy response in hypoxic prostate cancer xenografts. Manuscript, published in: Radiation Oncology 2011, 6:135. Published under a Creative Commons Attribution License. The published version of this paper is available at: https://doi.org/10.1186/1748-717X-6-135|