Paclitaxel/hydroxypropyl-β-cyclodextrin complex-loaded liposomes for overcoming multidrug resistance in cancer chemotherapy

J Liposome Res. 2020 Mar;30(1):12-20. doi: 10.1080/08982104.2019.1579838. Epub 2019 Mar 14.

Abstract

Multidrug resistance (MDR) is the largest obstacle to the success of chemotherapy. The development of innovative strategies and safe sensitizers is required to overcome MDR. Paclitaxel (PTX) is a widely used chemotherapeutic drug, the application of which has been learn to understand MDR. However, the application and use are severely restricted because of this MDR. Cyclodextrins (CDs) of many carriers, additionally have shown anti-cancer capability in MDR cancer cells. In this study, novel paclitaxel/hydroxypropyl-β-cyclodextrin complex-loaded liposomes (PTXCDL) have been developed in an attempt to overcome MDR in a PTX-resistant human lung adenocarcinoma (A549/T) cell line. The in vitro application of PTXCDL exhibited pH-sensitive PTX release, potent cytotoxicity, and enhanced intracellular accumulation. In comparison to in vivo, PTXCDL also show a stronger inhibition of tumor growth. In comparison, these findings suggest that the PTXCDL provide a novel strategy for effective therapy of resistant cancers by overcoming the drug resistance.

Keywords: Cancer chemotherapy; hydroxypropyl-β-cyclodextrin; multidrug resistance; paclitaxel; paclitaxel/hydroxypropyl-β-cyclodextrin complex-loaded liposomes.

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin / chemistry*
  • 2-Hydroxypropyl-beta-cyclodextrin / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Membrane Permeability
  • Cell Survival / drug effects
  • Cyclodextrins / chemistry*
  • Drug Compounding
  • Drug Liberation
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • Hydrogen-Ion Concentration
  • Liposomes / chemistry*
  • Nanoparticles / chemistry*
  • Paclitaxel / chemistry*
  • Paclitaxel / pharmacology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Cyclodextrins
  • Liposomes
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Paclitaxel