Journal
NANOMEDICINE
Volume 11, Issue 15, Pages 1947-1955Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2016-0147
Keywords
acid-labile docetaxel prodrug; blood-brain barrier; Particle Replication in Non-wetting Templates (PRINT)(R) PLGA nanoparticle
Funding
- Novartis
- Sanofi
- toBBB
- GERON
- Angio-chem
- Merrimack
- PUMA
- Lily
- Merck
- Oncothyreon
- National Cancer Institute [K23CA157728]
- Breast Cancer Research Foundation-AACR Grant for Translational Breast Cancer Research [10-60-26-ANDE]
- Damon Runyon Cancer Research Foundation [CI-64-12]
- Lineberger Comprehensive Cancer Center University of North Carolina SPORE Career Development Award [5P50CA058223]
- University Cancer Research Fund
- Carolina Center for Cancer Nanotechnology Excellence [U54CA151652]
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Aim: Particle Replication in Nonwetting Templates (PRINT (R)) PLGA nanoparticles of docetaxel and acid-labile C2-dimethyl-Si-Docetaxel were evaluated with small molecule docetaxel as treatments for non-small-cell lung cancer brain metastases. Materials & methods: Pharmacokinetics, survival, tumor growth and mice weight change were efficacy measures against intracranial A549 tumors in nude mice. Treatments were administered by intravenous injection. Results: Intracranial tumor concentrations of PRINT-docetaxel and PRINT-C2-docetaxel were 13- and sevenfold greater, respectively, than SM-docetaxel. C2-docetaxel conversion to docetaxel was threefold higher in intracranial tumor as compared with nontumor tissues. PRINT-C2-docetaxel increased median survival by 35% with less toxicity as compared with other treatments. Conclusion: The decreased toxicity of the PRINT-C2-docetaxel improved treatment efficacy against non-small-cell lung cancer brain metastasis.
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