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Programmable Codelivery of Doxorubicin and Apatinib Using an Implantable Hierarchical-Structured Fiber Device for

Yang He1, Xilin Li1, Junkai Ma2

  • 1Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.

Small (Weinheim an Der Bergstrasse, Germany)
|January 25, 2019
PubMed

Insights

A novel implantable fiber device delivers doxorubicin and apatinib to combat multidrug-resistant (MDR) cancer. This localized therapy enhances drug accumulation in tumors, improving efficacy and reducing systemic toxicity.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Multidrug resistance (MDR) in cancer is a significant barrier to chemotherapy effectiveness.
  • P-glycoprotein (P-gp) overexpression is a primary mechanism driving MDR, pumping therapeutic agents out of cancer cells.
  • Developing strategies to overcome P-gp mediated drug efflux is crucial for improving cancer treatment outcomes.

Purpose of the Study:

  • To develop an implantable device for localized co-delivery of doxorubicin (DOX) and apatinib (AP) to overcome MDR.
  • To investigate the controlled release kinetics of DOX and AP from the device.
  • To evaluate the in vivo efficacy and biodistribution of the dual-drug delivery system in MDR tumors.

Main Methods:

  • Fabrication of a hierarchical-structured ultrafine fiber device using microfluidic-electrospinning technology.
  • Encapsulation of doxorubicin (DOX) and apatinib (AP) with high efficiency (≈99%).
  • In vitro characterization of drug release profiles and in vivo assessment of drug biodistribution and antitumor effects in MDR tumor models.

Main Results:

  • The fiber device achieved high encapsulation efficiency for both DOX and AP.
  • A programmable release model was observed, with rapid release of DOX and sustained release of AP.
  • In vivo studies showed significantly enhanced DOX accumulation in tumor tissues (6.36-fold increase) and potent antitumor activity with low systemic toxicity.

Conclusions:

  • The developed implantable fiber device offers a promising strategy for localized co-delivery of chemotherapy drugs.
  • Sustained release of apatinib effectively inhibits P-gp, enhancing intracellular doxorubicin concentration and overcoming MDR.
  • This approach demonstrates significant potential for improving the therapeutic efficacy of chemotherapy against MDR cancers.
Keywords:
codeliveryelectrospun fiberslocalized administrationmicellesmultidrug resistance

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