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Multimodal nanoparticles that provide immunomodulation and intracellular drug delivery for infectious diseases

Admire Dube1, Jessica L Reynolds2, Wing-Cheung Law3

  • 1School of Pharmacy, University of Zimbabwe, Harare, Zimbabwe.

Nanomedicine : Nanotechnology, Biology, and Medicine
|December 17, 2013
PubMed

Insights

New nanoparticles combat tuberculosis by stimulating immune responses and delivering drugs directly to infected cells. This approach enhances the body's natural defenses and improves drug efficacy against Mycobacterium tuberculosis.

Area of Science:

  • Biomaterials Science
  • Immunology
  • Nanotechnology
  • Infectious Diseases

Background:

  • Infectious diseases, particularly tuberculosis (TB), pose a global health challenge, often involving intracellular pathogens like Mycobacterium tuberculosis that evade host immune responses.
  • Mycobacterium tuberculosis evades macrophage clearance by suppressing reactive oxygen and nitrogen species (ROS/RNS) and pro-inflammatory cytokines.
  • Current treatments face challenges due to pathogen intracellular residence and immune evasion mechanisms.

Purpose of the Study:

  • To propose and evaluate novel nanoparticle designs for treating infectious diseases, specifically TB.
  • To functionalize nanoparticles with ligands that modulate cellular immune responses and concurrently deliver antimicrobial drugs.
  • To investigate the efficacy of 1,3-β-glucan functionalized chitosan-poly(lactide)co-glycolide nanoparticles in stimulating immune responses and delivering rifampicin to macrophages.

Main Methods:

  • Design of 1,3-β-glucan functionalized chitosan shell, poly(lactide)co-glycolide core nanoparticles.
  • Functionalization with ligands to modulate immune response and deliver rifampicin.
  • In vitro testing using human alveolar-like macrophages (ALM) to assess ROS/RNS generation, cytokine secretion (IL-12p70, TNF-α, INF-γ), and intracellular drug delivery.

Main Results:

  • Nanoparticles significantly enhanced ALM secretion of IL-12p70 (2.9-fold), TNF-α (16-fold), and INF-γ (23-fold) over 24 hours compared to controls.
  • Nanoparticles doubled ROS/RNS generation in ALM over 6 hours.
  • Nanoparticles delivered 4-fold greater rifampicin into ALM compared to free rifampicin solution.

Conclusions:

  • The developed multimodal nanoparticles demonstrate proof-of-concept for stimulating immune responses and delivering drugs intracellularly.
  • These nanoparticles show significant potential for enhancing the treatment of intracellular infections like tuberculosis.
  • Further development of these functionalized nanoparticles is supported by the promising in vitro results.
Keywords:
1,3-β-glucanInfectious diseasesMultimodal nanoparticlesMycobacterium tuberculosisPLGA

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