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Cyclodextrin polymer improves atherosclerosis therapy and reduces ototoxicity.

Heegon Kim1, Junhee Han1, Ji-Ho Park1

  • 1Department of Bio and Brain Engineering and KAIST Institute for Health Science and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|December 18, 2019
PubMed
Summary

Polymerizing cyclodextrin (CD) into cyclodextrin polymer (CDP) improves drug delivery for atherosclerosis treatment. CDP shows better pharmacokinetics and reduced toxicity compared to monomeric CD, offering a promising therapeutic approach.

Keywords:
AtherosclerosisCyclodextrin polymerOtotoxicityPlaque therapy

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cardiovascular Research

Background:

  • Cyclodextrin (CD) shows potential for treating atherosclerotic plaques by solubilizing cholesterol.
  • However, poor pharmacokinetics and ototoxicity limit CD's therapeutic application.
  • Previous attempts to overcome these limitations are lacking.

Purpose of the Study:

  • To investigate the therapeutic potential of cyclodextrin polymer (CDP) as an alternative to monomeric CD for atherosclerosis.
  • To evaluate CDP's pharmacokinetics, plaque targeting, cytotoxicity, and efficacy in an atherosclerosis mouse model.

Main Methods:

  • Synthesis of cyclodextrin polymer (CDP) with a ~10 nm diameter.
  • Comparison of CDP and monomeric hydroxypropyl-beta-cyclodextrin (HPβCD) in vitro and in vivo.
  • Assessment of pharmacokinetics, plaque targeting, cytotoxicity, hemolytic activity, and ototoxicity in a mouse model of atherosclerosis.

Main Results:

  • CDP demonstrated superior pharmacokinetics and plaque targeting compared to monomeric CD.
  • CDP did not induce plasma membrane disruption, eliminating cytotoxicity and hemolytic activity.
  • Beta-cyclodextrin polymer (βCDP) significantly inhibited plaque growth in mice and showed no significant ototoxicity at high doses.

Conclusions:

  • Polymerization of cyclodextrin effectively overcomes the limitations of monomeric CD therapy.
  • CDP presents a promising, safer, and more effective therapeutic strategy for atherosclerosis treatment.