Abstract

Paclitaxel (PTX) is one of the drugs of choice in the treatment of breast and lung cancer. However, its severe side effects, including mielosuppression, cardiotoxicity and neurotoxicity, frequently cause treatment to be discontinued. Solid lipid nanoparticles (NPs) of glyceril tripalmitate (tripalmitin) loaded with PTX (Tripalm-NPs-PTX) including modifications by the addition of hexa(ethylene glycol), β-cyclodextrin and macelignan were developed. All NPs-PTX formulations displayed excellent hemocompatibility and significantly enhanced PTX antitumor activity in human breast (MCF7, MDAMB231, SKBR3 and T47D) and lung (A549, NCI-H520 and NCI-H460) cancer cells. Tripalm-NPs-PTX decreased PTX IC50 by as much as 40.5-fold in breast and 38.8-fold in lung cancer cells and Tripalm-NPs-PTX macelignan inhibited P-glycoprotein in resistant tumor cells. In addition, Tripalm-NPs-PTX significantly decreased the volume of breast and lung multicellular tumor spheroids that mimics in vivo tumor mass. Finally, Tripalm-NPs-PTX decreased the PTX IC50 of cancer stem cells (CSCs) derived from both lung and breast cancer cells (6.7- and 14.9-fold for MCF7 and A549 CSCs, respectively). These results offer a new PTX nanoformulation based on the use of tripalmitin which improves the antitumor activity of PTX and that may serve as an alternative PTX delivery system in breast and lung cancer treatment.

Details

Title
Tripalmitin nanoparticle formulations significantly enhance paclitaxel antitumor activity against breast and lung cancer cells in vitro
Author
Leiva, María Carmen 1 ; Ortiz, Raúl 2 ; Contreras-Cáceres, Rafael 3 ; Perazzoli, Gloria 4 ; Mayevych, Iryna 3 ; López-Romero, Juan Manuel 3 ; Sarabia, Francisco 3 ; Baeyens, Jose Manuel 5 ; Melguizo, Consolación 1 ; Prados, Jose 1 

 Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs. GRANADA), SAS-Universidad de Granada, Granada, Spain 
 Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Department of Health Science, University of Jaén, Jaén, Spain 
 Department of Organic Chemistry, Faculty of Science. University of Málaga, Málaga, Spain 
 Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain 
 Department of Pharmacology, Institute of Neuroscience, Biomedical Research Center (CIBM), University of Granada, Granada, Spain 
Pages
1-15
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2121473050
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.