Back to Journals » International Journal of Nanomedicine » Volume 9 » Issue 1

2'-(2-bromohexadecanoyl)-paclitaxel conjugate nanoparticles for the treatment of non-small cell lung cancer in an orthotopic xenograft mouse model

Authors Peng L, Schorzman AN, Ma P, Madden AJ, Zamboni WC, Benhabbour SR, Mumper RJ

Received 12 April 2014

Accepted for publication 15 May 2014

Published 30 July 2014 Volume 2014:9(1) Pages 3601—3610

DOI https://doi.org/10.2147/IJN.S66040

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Lei Peng,1 Allison N Schorzman,2 Ping Ma,1 Andrew J Madden,2 William C Zamboni,2–4 Soumya Rahima Benhabbour,1 Russell J Mumper1,4

1Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 2Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 3Center for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, 4UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina, NC, USA

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.

Keywords: tubulin polymerization, pharmacokinetic, maximum tolerated dose, efficacy, pleural fluid, bioluminescence imaging, A549 cell tumor model

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other article by this author:

Lipid nanoparticles with accessible nickel as a vaccine delivery system for single and multiple his-tagged HIV antigens

Weili Yan, Anekant Jain, Ronan O’Carra,  Jerold G Woodward, et al.

HIV/AIDS - Research and Palliative Care 2009, 1:1-11

Published Date: 17 July 2009

Readers of this article also read:

Real-world evaluation of compliance and preference in Alzheimer’s disease treatment

Pai MC, Aref H, Bassil N, Kandiah N, Lee JH, Srinivasan AV, diTommaso S, Yuksel O

Clinical Interventions in Aging 2015, 10:1779-1788

Published Date: 3 November 2015

Improving access to shared decision-making for Hispanics/Latinos with inadequately controlled type 2 diabetes mellitus

Davidson JA, Rosales A, Shillington AC, Bailey RA, Kabir C, Umpierrez GE

Patient Preference and Adherence 2015, 9:619-625

Published Date: 30 April 2015

Efficacy of intensity-modulated radiotherapy combined with chemotherapy or surgery in locally advanced squamous cell carcinoma of the head-and-neck

Yang H, Diao LQ, Shi M, Ma R, Wang JH, Li JP, Xiao F, Xue Y, Xu M, Zhou B

Biologics: Targets and Therapy 2013, 7:223-229

Published Date: 18 October 2013

The use of PEGylated liposomes in the development of drug delivery applications for the treatment of hemophilia

Rivka Yatuv, Micah Robinson, Inbal Dayan-Tarshish, et al

International Journal of Nanomedicine 2010, 5:581-591

Published Date: 6 August 2010

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010