Title |
2'-(2-bromohexadecanoyl)-paclitaxel conjugate nanoparticles for the treatment of non-small cell lung cancer in an orthotopic xenograft mouse model
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Published in |
International Journal of Nanomedicine, July 2014
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DOI | 10.2147/ijn.s66040 |
Pubmed ID | |
Authors |
Lei Peng, Allison N Schorzman, Ping Ma, Andrew J Madden, William C Zamboni, Soumya Rahima Benhabbour, Russell J Mumper |
Abstract |
A nanoparticle (NP) formulation with 2'-(2-bromohexadecanoyl)-paclitaxel (Br-16-PX) conjugate was developed in these studies for the treatment of non-small cell lung cancer (NSCLC). The lipophilic paclitaxel conjugate Br-C16-PX was synthesized and incorporated into lipid NPs where the 16-carbon chain enhanced drug entrapment in the drug delivery system and improved in vivo pharmacokinetics. The electron-withdrawing bromine group was used to facilitate the conversion of Br-C16-PX to paclitaxel at the tumor site. The developed system was evaluated in luciferase-expressing A549 cells in vitro and in an orthotopic NSCLC mouse model. The results demonstrated that the Br-C16-PX NPs had a higher maximum tolerated dose (75 mg/kg) than Taxol (19 mg/kg) and provided significantly longer median survival (88 days versus 70 days, P<0.05) in the orthotopic NSCLC model. An improved pharmacokinetic profile was observed for the Br-C16-PX NPs at 75 mg/kg compared to Taxol at 19 mg/kg. The area under the concentration versus time curve (AUC)₀₋₉₆ h of Br-C16-PX from the NPs was 91.7-fold and 49.6-fold greater than Taxol in plasma and tumor-bearing lungs, respectively, which provided sustained drug exposure and higher antitumor efficacy in the NP-treated group. |
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Geographical breakdown
Country | Count | As % |
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Unknown | 21 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 5 | 24% |
Student > Master | 4 | 19% |
Student > Doctoral Student | 2 | 10% |
Student > Bachelor | 1 | 5% |
Other | 1 | 5% |
Other | 2 | 10% |
Unknown | 6 | 29% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 2 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 10% |
Agricultural and Biological Sciences | 2 | 10% |
Chemistry | 2 | 10% |
Other | 0 | 0% |
Unknown | 8 | 38% |