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Poly(L-lactide) Nanoparticles Reduce Amphotericin B Cytotoxicity and Maintain Its In Vitro Antifungal Activity

Diani Meza Casa, Talita Cristina Moreira Moraes Carraro, Luciana Erzinger Alves de Camargo

    Journal of Nanoscience and Nanotechnology
    |September 3, 2015
    PubMed

    Insights

    Poly(L-lactide) nanoparticles effectively deliver amphotericin B, reducing toxicity to red blood cells while maintaining antifungal efficacy against Candida species.

    Area of Science:

    • Biomaterials Science
    • Pharmaceutical Sciences
    • Mycology

    Background:

    • Amphotericin B (AmB) is a potent antifungal agent but exhibits significant toxicity, particularly hemolysis.
    • Developing effective drug delivery systems is crucial to mitigate AmB's side effects and improve therapeutic outcomes.
    • Poly(L-lactide) (PLA) nanoparticles offer a promising platform for encapsulating and delivering therapeutic agents.

    Purpose of the Study:

    • To develop and characterize poly(L-lactide) (PLA) nanoparticles loaded with amphotericin B (AmB).
    • To evaluate the in vitro cytotoxicity of AmB-loaded PLA nanoparticles on human erythrocytes.
    • To assess the antifungal efficacy of AmB-loaded PLA nanoparticles against Candida species and their release profile.

    Main Methods:

    • Nanoparticles were prepared using an emulsion/solvent evaporation method.
    • Characterization included particle size, size distribution, AmB encapsulation efficiency, aggregation state, and in vitro release kinetics.
    • Cytotoxicity was assessed by measuring the hemolysis index, and antifungal activity was tested against Candida spp.

    Main Results:

    • PLA nanoparticles exhibited a mean particle size of 225 nm with an AmB encapsulation efficiency exceeding 69%.
    • A burst release of ~10% AmB occurred within 24 hours, followed by sustained release (~30%) over 30 days.
    • AmB-loaded PLA nanoparticles showed significantly reduced hemolysis compared to free AmB, with comparable antifungal efficacy against Candida strains.

    Conclusions:

    • PLA nanoparticles provide a viable strategy for formulating AmB with diminished erythrocyte toxicity.
    • The sustained release profile of AmB from PLA nanoparticles maintains antifungal activity.
    • PLA nanoparticles represent a promising delivery system for improving the therapeutic index of amphotericin B.

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