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

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 ?-elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, ?-elemene liposome and cabazitaxel-?-elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and ?-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 ?-elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and ?-elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and ?-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 ?-elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.

SUBMITTER: Zeng YY

PROVIDER: S-EPMC6539285 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Zeng Yi-Ying YY Zeng Yi-Jun YJ Zhang Na-Na NN Li Chen-Xi CX Xie Tian T Zeng Zhao-Wu ZW

Molecules (Basel, Switzerland) 20190430 9

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 comp ...[more]

PMID: 31052317

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Project description:Background:Breast cancer is the leading cause of cancer death in women. Chemotherapy to inhibit the proliferation of cancer cells is considered to be the most important therapeutic strategy. The development of long-circulating PEG and targeting liposomes is a major advance in drug delivery. However, the techniques used in liposome preparation mainly involve conventional liposomes, which have a short half-life, high concentrations in the liver and spleen reticuloendothelial system, and no active targeting. Methods:Four kinds of paclitaxel liposomes were prepared and characterized by various analytical techniques. The long-term targeting effect of liposomes was verified by fluorescence detection methods in vivo and in vitro. Pharmacokinetic and acute toxicity tests were conducted in ICR mice to evaluate the safety of different paclitaxel preparations. The antitumor activity of ES-SSL-PTX was investigated in detail using in vitro and in vivo human breast cancer MCF-7 cell models. Results:ER-targeting liposomes had a particle size of 137.93±1.22 nm and an acceptable encapsulation efficiency of 88.07±1.25%. The liposome preparation is best stored at 4°C, and is stable for up to 48 hrs. Cytotoxicity test on MCF-7 cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. We used the near-infrared fluorescence imaging technique to confirm that ES-SSL-PTX was effectively targeted and could quickly and specifically identify the tumor site. Pharmacokinetics and acute toxicity in vivo experiments were carried out. The results showed that ES-SSL-PTX could significantly prolong the half-life of the drug, increase its circulation time in vivo, improve its bioavailability and reduce its toxicity and side effects. ES-SSL-PTX can significantly improve the pharmacokinetic properties of paclitaxel, avoid allergic reaction of the original solvent, increase antitumor efficacy and reduce drug toxicity and side effects. Conclusion:ES-SSL-PTX has great potential for improving the treatment of breast cancer, thereby improving patient prognosis and quality of life.

Dataset Information

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

Publications

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

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