Tripalmitin nanoparticle formulations significantly enhance paclitaxel antitumor activity against breast and lung cancer cells in vitro

María Carmen Leiva,Francisco Sarabia,Consolación Melguizo,Iryna Mayevych,Rafael Contreras-Cáceres,Jose Manuel Baeyens,Juan Manuel López-Romero,Jose Prados,Gloria Perazzoli,Raúl Ortiz

doi:10.1038/s41598-017-13816-z

María Carmen Leiva, Francisco Sarabia + Show 8 more

Open Access

https://doi.org/10.1038/s41598-017-13816-z

Copy DOI

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.

Highlights

Paclitaxel (PTX) has been proved to have excellent antitumor properties against breast and lung cancer
Our results showed that the new PTX-loaded solid lipid NPs improve the PTX effect in comparison to the free drug in culture cells and multicellular tumor spheroids (MTS) and in cancer stem cells (CSCs) derived from both type of tumors
Tripalm-NPs-PTX were able to significantly reduce the PTX IC50 on breast and lung cancer cells, providing a greater cytotoxic effect. This increased antitumor activity was corroborated using MTS, where Tripalm-NPs-PTX significantly decreased the volume of both breast and lung MTS

Summary

Introduction

Paclitaxel (PTX) has been proved to have excellent antitumor properties against breast and lung cancer. Baek and Cho[23] modified solid lipid PTX-loaded NPs through the incorporation of 2-hydroxypropyl-βCD resulting in an increased drug internalization and cell death in the resistant MCF-7/ADR breast cancer cell line and a decrease in drug toxicity after intravenous injection. Our work represent the first study of a glyceryltripalmitate solid lipid NPs designed as a paclitaxel delivery system (Tripalm-NPs-PTX) to the breast and lung cancer treatment including assays in culture cells, multicellular tumor spheroids and cancer stem cells. The main objective of this study was to develop, characterize and assay PTX-loaded glyceryl tripalmitate solid lipid NPs (Tripalm-NPs-PTX) to significantly increase their antitumor effect and permeability in comparison to the free drug in both breast and lung human cancer cells cultures and multicellular tumor spheroids (MTS), an experimental system that mimics tumours in vivo. Our results showed that the new PTX-loaded solid lipid NPs improve the PTX effect in comparison to the free drug in culture cells and MTS and in CSCs derived from both type of tumors

Objectives

Methods

Results

Conclusion