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  Gemcitabine treatment of rat soft tissue sarcoma with phosphatidyldiglycerol-based thermosensitive liposomes.

Limmer, S., Hahn, J., Schmidt, R., Wachholz, K., Zengerle, A., Lechner, K., et al. (2014). Gemcitabine treatment of rat soft tissue sarcoma with phosphatidyldiglycerol-based thermosensitive liposomes. Pharmaceutical Research, 31(9), 2276-2286. doi:10.1007/s11095-014-1322-6.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0024-301C-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CDD3-2
Genre: Journal Article

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 Creators:
Limmer, S., Author
Hahn, J., Author
Schmidt, R., Author
Wachholz, K., Author
Zengerle, A., Author
Lechner, K., Author
Eibl, H. J.1, Author              
Issels, R. D., Author
Hossann, M., Author
Lindner, L. H., Author
Affiliations:
1Research Group of Phospholipids, MPI for biophysical chemistry, Max Planck Society, ou_578562              

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Free keywords: drug delivery; gemcitabine; hyperthermia; phosphatidyloligoglycerol; thermosensitive liposomes
 Abstract: The pyrimidine analogue gemcitabine (dFdC) is frequently used in the treatment of patients with solid tumors. However, after i.v. application dFdC is rapidly inactivated by metabolization. Here, the potential of thermosensitive liposomes based on 1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol (DPPG(2)-TSL) were investigated as carrier and targeting system for delivery of dFdC in combination with local hyperthermia (HT). DPPG(2)-TSL were prepared by the lipid film hydration and extrusion method and characterized by dynamic light scattering, thin layer chromatography, phosphate assay and HPLC. In vivo experiments were performed in Brown Norway rats with a syngeneic soft tissue sarcoma. Local HT treatment was performed by light exposure. DPPG(2)-TSL were stable at 37A degrees C in serum and showed a temperature dependent dFdC release > 40A degrees C. Plasma half-life of dFdC was strongly increased from 0.07 h (non-liposomal) to 0.53 h (liposomal, vesicle size 105 nm) or 2.59 h (liposomal, 129 nm). Therapy of BN175 tumors with dFdC encapsulated in DPPG(2)-TSL + HT showed significant improvement in tumor growth delay compared to non-liposomal dFdC without HT (p < 0.05), non-liposomal dFdC with HT (p < 0.01), and liposomal dFdC without HT (p < 0.05), respectively. Gemcitabine encapsulated in DPPG(2)-TSL in combination with local HT is a promising tool for the treatment of solid tumors. Therefore, these encouraging results ask for further investigation and evaluation.

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Language(s): eng - English
 Dates: 2014-03-062014-09
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1007/s11095-014-1322-6
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Title: Pharmaceutical Research
Source Genre: Journal
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Pages: - Volume / Issue: 31 (9) Sequence Number: - Start / End Page: 2276 - 2286 Identifier: -