Novel drug combination nanoparticles exhibit enhanced plasma exposure and dose-responsive effects on eliminating breast cancer lung metastasis.

PloS One
Qingxin MuRodney J Y Ho

Abstract

Early diagnosis along with new drugs targeted to cancer receptors and immunocheckpoints have improved breast cancer survival. However, full remission remains elusive for metastatic breast cancer due to dose-limiting toxicities of heavily used, highly potent drug combinations such as gemcitabine and paclitaxel. Therefore, novel strategies that lower the effective dose and improve safety margins could enhance the effect of these drug combinations. To this end, we developed and evaluated a novel drug combination of gemcitabine and paclitaxel (GT). Leveraging a simple and scalable drug-combination nanoparticle platform (DcNP), we successfully prepared an injectable GT combination in DcNP (GT DcNP). Compared to a Cremophor EL/ethanol assisted drug suspension in buffer (CrEL), GT DcNP exhibits about 56-fold and 8.6-fold increases in plasma drug exposure (area under the curve, AUC) and apparent half-life of gemcitabine respectively, and a 2.9-fold increase of AUC for paclitaxel. Using 4T1 as a syngeneic model for breast cancer metastasis, we found that a single GT (20/2 mg/kg) dose in DcNP nearly eliminated colonization in the lungs. This effect was not achievable by a CrEL drug combination at a 5-fold higher dose (i.e., 100/10 mg/kg ...Continue Reading

References

Aug 8, 2006·Nature Medicine·Patricia S Steeg
Apr 25, 2008·Current Protocols in Immunology·B A Pulaski, S Ostrand-Rosenberg
Aug 12, 2008·BMC Cancer·Kai TaoG Gary Sahagian
Aug 20, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kathy S AlbainJoyce O'Shaughnessy
Feb 27, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Donatella PaolinoMassimo Fresta
Oct 5, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick J LoehrerAl B Benson
Jun 2, 2012·Nature Reviews. Drug Discovery·Bedrich L EckhardtRobin L Anderson
Nov 25, 2014·Expert Opinion on Drug Metabolism & Toxicology·Omar M Rashid, Kazuaki Takabe
Jan 20, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Haiqiang CaoYaping Li
Dec 10, 2016·Cancer Metastasis Reviews·Bora Lim, Gabriel N Hortobagyi
Nov 9, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jing ZhangYi Jin
Jan 9, 2019·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal

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