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Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
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Development of Polymersomes Co-Delivering Doxorubicin and Melittin to Overcome Multidrug Resistance

Eunkyung Han1, Doyeon Kim1, Youngheun Cho1

  • 1Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea.

Molecules (Basel, Switzerland)
|February 11, 2023
PubMed

Insights

This study developed a novel polymersome to overcome multidrug resistance (MDR) in cancer chemotherapy. By co-delivering doxorubicin and melittin, it effectively downregulates P-glycoprotein (P-gp) and enhances treatment efficacy.

Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Cancer Biology

Background:

  • Multidrug resistance (MDR) is a significant challenge in chemotherapy, often caused by P-glycoprotein (P-gp) overexpression.
  • P-gp efflux pumps reduce the intracellular concentration of anticancer drugs, leading to treatment failure.
  • Activated PI3K/Akt and NF-kB signaling pathways are implicated in P-gp-mediated MDR.

Purpose of the Study:

  • To develop a novel polymersome for co-delivery of doxorubicin and melittin.
  • To overcome P-gp-mediated MDR and enhance chemotherapeutic efficacy.
  • To investigate the role of melittin in downregulating MDR-related pathways.

Main Methods:

  • Fabrication of a polymersome using a poly(lactic acid)-hyaluronic acid (PLA-HA) di-block copolymer.
  • Encapsulation of doxorubicin (anticancer drug) and melittin (bee venom component) within the polymersome.
  • Evaluation of the polymersome's efficacy in overcoming MDR in relevant cancer models.

Main Results:

  • The developed polymersome successfully co-delivered doxorubicin and melittin.
  • Simultaneous delivery inhibited PI3K/Akt and NF-kB pathways, crucial in MDR.
  • Downregulation of P-gp expression was observed, leading to enhanced chemotherapeutic efficacy.

Conclusions:

  • A polymersome co-delivering an anticancer drug and melittin is a promising strategy to overcome MDR.
  • This approach effectively targets P-gp overexpression pathways.
  • The developed nanocarrier enhances chemotherapy effectiveness against resistant cancers.
Keywords:
PI3K/Akt/NF-kBdoxorubicinmelittinmultidrug resistancepolymersome

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