Research Article
Liposome formulation of co-encapsulated vincristine and quercetin enhanced antitumor activity in a trastuzumab-insensitive breast tumor xenograft model
Graphical Abstract
In vivo antitumor effects of various treatment groups against JIMT-1 xenografts.
Section snippets
Materials
All lipids were obtained from Avanti Polar Lipids (Alabaster, Alabama). JIMT-1 cells were obtained from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (Braunschweig, Germany). The materials 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), dimethylsulfoxide (DMSO) and chloroform were purchased from MP Biomedicals Asia Pacific Pte Ltd (Singapore). Balb/c mice were supplied via the Centre for Animal Resources, National University of Singapore (Singapore), and SCID
In vitro combination effects of free vincristine and quercetin
Previously, we showed that the most synergistic molar ratio of vincristine and quercetin was 2:1 in MDA-MB-231 cells.15 Given that it is important to demonstrate consistent display of synergy across different cell lines for a specific ratio of chemotherapeutic agents,24 it was our aim to assess if a similar trend could be observed in JIMT-1 cells. The in vitro combination effects of vincristine and quercetin were compared among the molar drug ratios of 4:1, 2:1, 1:1 and 1:2. Figure 1 shows the
Discussion
We will discuss our work from the formulation and clinical perspectives. From the formulation perspective, we have demonstrated that the administration of free drug combination in the absence of a drug carrier led to antagonistic CI values in vivo. This highlights the need for a delivery vehicle to attain optimal antitumor efficacy for the vincristine/quercetin combination. Liposomal co-encapsulation of vincristine and quercetin maintained the optimal synergistic drug ratio in plasma to be
References (32)
- et al.
ER-negative and triple negative breast cancer: molecular features and potential therapeutic approaches
Biochim Biophys Acta - Rev Cancer
(2009) - et al.
In vivo maintenance of synergistic cytarabine:daunorubicin ratios greatly enhances therapeutic efficacy
Leuk Res
(2009) - et al.
Coencapsulation of irinotecan and floxuridine into low cholesterol-containing liposomes that coordinate drug release in vivo
Biochim Biophys Acta (BBA) - Biomembranes
(2007) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays
J Immunol Methods
(1983)- et al.
A simple generalized equation for the analysis of multiple inhibitions of Michaelis-Menten kinetic systems
J Biol Chem
(1977) - et al.
Characterization of liposomal systems containing doxorubicin entrapped in response to pH gradients
Biochim Biophys Acta
(1990) - et al.
Ionophore-mediated uptake of ciprofloxacin and vincristine into large unilamellar vesicles exhibiting transmembrane ion gradients
Biochim Biophys Acta (BBA) - Biomembranes
(1998) - et al.
Preparation, characterization, and biological analysis of liposomal formulations of vincristine
- et al.
Dual agents loaded PLGA nanoparticles: systematic study of particle size and drug entrapment efficiency
Eur J Pharm Biopharm
(2008) - et al.
Relationships between tumor responsiveness, vincristine pharmacokinetics and arrest of mitosis in human tumor xenografts
Biochem Pharmacol
(1988)
Global Cancer Statistics, 2002
CA Cancer J Clin
Adjuvant therapy for breast cancer
Minerva Ginecol
Current and emerging treatment options in triple-negative breast cancer
Oncol Rev
Definition of an optimal first-line chemotherapy in metastatic breast cancer
Breast Cancer Res Treat
Diffusion of univalent ions across the lamellae of swollen phospholipids
J Mol Biol
Liposomal, Nanoparticle, and conjugated formulations of anticancer agents
Clin Cancer Res
Cited by (0)
-
This work was supported by the Singapore Ministry of Education via the National University of Singapore Academic Research Fund (grant # R-148-050-077-101 & R-148-050-077-133). Man-Yi Wong is a recipient of a research scholarship from Singapore Ministry of Education.
-
There are no conflicts of interest in connection with this article.