Paclitaxel- and lapatinib-loaded lipopolymer micelles overcome multidrug resistance in prostate cancer

Drug Delivery and Translational Research
Feng LiRam I Mahato

Abstract

Paclitaxel is a potent chemotherapeutic agent for treating refractory prostate cancer. However, its prolonged treatment develops multidrug resistance. Since lapatinib interacts with and inhibits P-gp activity, our objective was to determine whether the combination therapy of these two drugs can synergistically treat resistant prostate cancer. Our recently synthesized lipopolymer, poly(ethylene glycol)-block-poly(2-methyl-2-carboxylpropylene carbonate-graft-dodecanol) (PEG-PCD), was used to efficiently load both drugs into PEG-PCD micelles since they are hydrophobic. Lapatinib inhibited P-gp function but not its expression. Co-treatment of DU145-TXR cells with 0.5 μM paclitaxel and 5 μM lapatinib resulted in up to 138-fold reversal compared to paclitaxel alone. These formulations killed almost 70% and 80% of DU145-TXR cells when 0.5 μM paclitaxel was combined with lapatinib at a dose of 1 and 5 μM, respectively, while monotherapy had no effect. Combination therapy induced apoptosis and cell cycle arrest at mitotic phase. Xenograft tumor growth in athymic nude mice was significantly regressed when PEG-PCD micelles carrying lapatinib and paclitaxel were given intravenously twice a week. Furthermore, this combination therapy synerg...Continue Reading

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Citations

Mar 28, 2012·Pharmaceutical Research·Michael DanquahRam I Mahato
Oct 18, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hongxiang HuQiang Zhang
Mar 22, 2015·Drug Delivery and Translational Research·Dwayne Koot, Duncan Cromarty
Nov 1, 2016·Drug Development and Industrial Pharmacy·Pouya DehghankelishadiFarid Abedin Dorkoosh
Mar 4, 2017·Materials Science & Engineering. C, Materials for Biological Applications·Rezvan MobasseriSeeram Ramakrishna
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Sep 23, 2020·Advanced Healthcare Materials·Jason V GregoryJoerg Lahann
Jun 10, 2016·International Journal of Oncology·Jing LiJian Zhang
Dec 10, 2020·International Journal of Molecular Sciences·Shani L LevitChristina Tang
Mar 17, 2020·Asian Journal of Pharmaceutical Sciences·Xiaohan ZhouZhiyong Qian
Jan 11, 2014·Molecular Pharmaceutics·Huiyuan WangYongzhuo Huang

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