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Microwave-assisted Functionalization of Polyethylene glycol and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation
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Reducing the toxicity of amphotericin B by encapsulation using methoxy poly(ethylene glycol)-b-poly(l-glutamic

Chenguang Yang1, Baiji Xue, Wantong Song

  • 1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China. ztang@ciac.ac.cn.

Biomaterials Science
|June 28, 2018
PubMed

Insights

This study developed a new nanoparticle formulation of Amphotericin B (AmB) to reduce its toxicity. The new formulation, l-AmB, demonstrated significantly lower side effects and improved therapeutic efficacy against fungal infections compared to free AmB.

Area of Science:

  • Nanomedicine
  • Pharmacology
  • Biochemistry

Background:

  • Amphotericin B (AmB) is a critical antifungal agent for severe infections.
  • High toxicity limits the clinical use of Amphotericin B.
  • Developing safer AmB formulations is crucial for effective treatment.

Purpose of the Study:

  • To develop a novel nanoparticle formulation of Amphotericin B (AmB).
  • To reduce the toxicity and improve the therapeutic index of AmB.
  • To evaluate the stability, safety, and efficacy of the new AmB formulation.

Main Methods:

  • Encapsulation of AmB into mPEG-b-P(Glu-co-Phe) nanoparticles (l-AmB).
  • Assessment of nanoparticle stability in PBS and plasma.
  • Evaluation of hemolysis, nephrotoxicity, and maximum tolerance dose (MTD).
  • In vivo efficacy testing against Aspergillus fumigatus infections in mice.

Main Results:

  • l-AmB nanoparticles exhibited excellent stability.
  • Significantly reduced hemolysis (17.1%) compared to free AmB (94.2%).
  • l-AmB showed substantially lower nephrotoxicity and a 3.75-fold higher MTD than free AmB.
  • l-AmB retained antimicrobial activity and provided superior protection against fungal infections in mice.

Conclusions:

  • The developed l-AmB nanoparticle formulation effectively reduces AmB toxicity.
  • l-AmB offers improved safety and enhanced therapeutic efficacy.
  • This formulation represents a promising strategy for treating serious fungal infections with reduced side effects.

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