NDLI: Biodistribution and Efficacy of Low Temperature-Sensitive Liposome Encapsulated Docetaxel Combined with Mild Hyperthermia in a Mouse Model of Prostate Cancer

Content Provider	Springer Nature Link
Author	Ranjan, Ashish Benjamin, Compton J. Negussie, Ayele H. Chokshi, Saurin Chung, Paul H. Volkin, Dmitry Yeram, Nitin Linehan, W. Marston Dreher, Matthew R. Pinto, Peter A. Wood, Bradford J.
Copyright Year	2016
Abstract	Low temperature sensitive liposome (LTSL) encapsulated docetaxel were combined with mild hyperthermia (40–42°C) to investigate in vivo biodistribution and efficacy against a castrate resistant prostate cancer.Female athymic nude mice with human prostate PC-3 M-luciferase cells grown subcutaneously into the right hind leg were randomized into six groups: saline (+/− heat), free docetaxel (+/− heat), and LTSL docetaxel (+/− heat). Treatment (15 mg docetaxel/kg) was administered via tail vein once tumors reached a size of 200-300 mm$^{3}$. Mice tumor volumes and body weights were recorded for up to 60 days. Docetaxel concentrations of harvested tumor and organ/tissue homogenates were determined by LC-MS. Histological evaluation (Mean vessel density, Ki67 proliferation, Caspase-3 apoptosis) of saline, free Docetaxel and LTSL docetaxel (+/− heat n = 3–5) was performed to determine molecular mechanism responsible for tumor cell killing.LTSL/heat resulted in significantly higher tumor docetaxel concentrations (4.7-fold greater compared to free docetaxel). Adding heat to LTSL Docetaxel or free docetaxel treatment resulted in significantly greater survival and growth delay compared to other treatments (p < 0.05). Differences in body weight between all Docetaxel treatments were not reduced by >10% and were not statistically different from each other. Molecular markers such as caspase-3 were upregulated, and Ki67 expression was significantly decreased in the chemo-hyperthermia group. Vessel density was similar post treatment, but the heated group had reduced vessel area, suggesting thermal enhancement in efficacy by reduction in functional perfusion.This technique of hyperthermia sensitization and enhanced docetaxel delivery has potential for clinical translation for prostate cancer treatment.
Starting Page	2459
Ending Page	2469
Page Count	11
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	33
Issue Number	10
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2016-06-24
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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