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

Molecules. 2019 Apr 30;24(9):1697. doi: 10.3390/molecules24091697.

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.

Keywords: cabazitaxel; liposome; lung adenocarcinoma; paclitaxel resistance; β-elemene.

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / pathology
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols
  • Cell Line, Tumor
  • Disease Models, Animal
  • Drug Resistance, Neoplasm*
  • Humans
  • Liposomes* / chemistry
  • Mice
  • Molecular Structure
  • Paclitaxel / pharmacology
  • Particle Size
  • Sesquiterpenes / administration & dosage*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacokinetics*
  • Taxoids / administration & dosage*
  • Taxoids / chemistry
  • Taxoids / pharmacokinetics*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Liposomes
  • Sesquiterpenes
  • Taxoids
  • beta-elemene
  • cabazitaxel
  • Paclitaxel