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Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages

Susana P Mejía1,2, Daniela López2, Luz Elena Cano2

  • 1Max Planck Tandem Group in Nanobioengineering, Institute of Chemistry, Faculty of Natural and Exact Sciences, University of Antioquia, Complejo Ruta N, Calle 67 N° 52-20, Medellin 050010, Colombia.

Pharmaceutics
|September 23, 2022
PubMed

Insights

Targeted nanoparticles carrying Itraconazole (ITZ) effectively eliminated the intracellular fungus Histoplasma capsulatum in macrophages. This novel approach enhances drug delivery and antifungal response, offering a promising strategy for infectious disease treatment.

Area of Science:

  • Nanomedicine
  • Infectious Diseases
  • Immunology

Background:

  • Infectious diseases caused by intracellular microorganisms like Histoplasma capsulatum pose global health challenges.
  • Drug encapsulation in nanoparticles (NPs) improves drug delivery, bioavailability, and targeted action.

Purpose of the Study:

  • To develop and evaluate anti-F4/80 antibody-functionalized polymeric nanoparticles (NPs) for targeted delivery of Itraconazole (ITZ) to macrophages.
  • To assess the efficacy of ITZ-loaded NPs against H. capsulatum in vitro and their impact on macrophage inflammatory responses.

Main Methods:

  • Core-shell polymeric NPs were synthesized encapsulating Itraconazole (ITZ).
  • NPs were functionalized with anti-F4/80 antibodies for macrophage targeting.
  • In vitro assays evaluated NP uptake, antifungal activity against H. capsulatum, and cytotoxicity in macrophages.
  • Gene expression of inflammatory cytokines (IL-1, INF-Y, IL-6, IL-10) was analyzed.

Main Results:

  • Functionalized NPs showed significantly higher uptake by macrophages compared to bare NPs.
  • Anti-F4/80 antibody-functionalized NPs loaded with 0.007 µg/mL ITZ effectively eliminated H. capsulatum without macrophage cytotoxicity.
  • Encapsulated ITZ modulated the expression of anti-inflammatory and pro-inflammatory cytokines.
  • Antibody functionalization enhanced the natural antifungal response and exerted a synergistic effect, inhibiting intracellular fungal growth.

Conclusions:

  • Anti-F4/80 antibody-functionalized NPs offer a promising strategy for targeted macrophage therapy against intracellular pathogens like H. capsulatum.
  • This approach enhances NP endocytosis and intracellular drug concentration, leading to improved therapeutic outcomes.
  • The synergistic effect of targeted drug delivery and enhanced host response presents a novel avenue for infectious disease treatment.
Keywords:
F4/80 receptorHistoplasma capsulatumItraconazolePLGAfunctionalized nanoparticlemacrophage

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