The Preparation, Determination of a Flexible Complex Liposome Co-Loaded with Cabazitaxel and β-Elemene, and Animal Pharmacodynamics on Paclitaxel-Resistant Lung Adenocarcinoma

卡巴他赛与β-榄香烯共载柔性复合脂质体的制备、含量测定及对紫杉醇耐药肺腺癌动物药效学研究

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作者:Yi-Ying Zeng, Yi-Jun Zeng, Na-Na Zhang, Chen-Xi Li, Tian Xie, Zhao-Wu Zeng0

Abstract

Paclitaxel is highly effective at killing many malignant tumors; however, the development of drug resistance is common in clinical applications. The issue of overcoming paclitaxel resistance is a difficult challenge at present. In this study, we developed nano drugs to treat paclitaxel-resistant lung adenocarcinoma. We selected cabazitaxel and β-elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, β-elemene liposome and cabazitaxel-β-elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and β-elemene in these liposomes were detected by precipitation microfiltration and microfiltration centrifugation methods, respectively. Their encapsulation efficiencies were all above 95%. The release rates were detected by a dialysis method. The release profiles of cabazitaxel and β-elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and β-elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and β-elemene flexible liposome were relatively good at overcoming paclitaxel resistance on paclitaxel-resistant lung adenocarcinoma. As the flexible complex liposome, the dosage of cabazitaxel could be reduced to 25% that of the cabazitaxel injection while retaining a similar therapeutic effect. It showed that β-elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.

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