Lipase-Responsive Amphotericin B Loaded PCL Nanoparticles for Antifungal Therapies

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Abstract

Amphotericin B is an antifungal drug used for the treatment of invasive fungal infections. However, its clinical use is limited due to its serious side effects, such as renal and cardiovascular toxicity. Furthermore, amphotericin B is administered in high doses due to its poor water solubility. Hence, it is necessary to develop an on-demand release strategy for the delivery of amphotericin B to reduce cytotoxicity. The present report describes a novel encapsulation of amphotericin B into lipase-sensitive polycaprolactone to form a nanocomposite. Nanocomposites were produced by the oil-in-water method and their physicochemical properties such as size, hydrodynamic diameter, drug loading, and zeta potential were determined. The in vitro release of amphotericin B was characterized in the presence and absence of lipase. The antifungal activity of the nanocomposites was verified against lipase-secreting Candida albicans, and cytotoxicity was tested against primary human dermal fibroblasts. In the absence of lipase, the release of amphotericin B from the nanocomposites was minimal. However, in the presence of lipase, an enzyme that is abundant at infection sites, a fungicidal concentration of amphotericin B was released from the nanocomposites. The antifungal activity of the nanocomposites showed an enhanced effect against the lipase-secreting fungus, Candida albicans, in comparison to the free drug at the same concentration. Furthermore, nanoencapsulation significantly reduced amphotericin B-related cytotoxicity compared to the free drug. The synthesized nanocomposites can serve as a potent carrier for the responsive delivery of amphotericin B in antifungal applications.

Original languageEnglish
Article number155
Number of pages14
JournalNanomaterials
Volume13
Issue number1
Early online date29 Dec 2022
DOIs
Publication statusPublished - 1 Jan 2023

Keywords

  • amphotericin B
  • antifungal activity
  • cytocompatible
  • drug delivery
  • lipase
  • polycaprolactone (PCL)

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