Physicochemical and Biological Evaluation of Curdlan-Poly(Lactic-Co-Glycolic Acid) Nanoparticles as a Host-Directed Therapy Against Mycobacterium Tuberculosis

J Pharm Sci. 2022 Feb;111(2):469-478. doi: 10.1016/j.xphs.2021.09.012. Epub 2021 Sep 14.


Nanoparticles (NPs) that can activate macrophages infected with the tuberculosis causative pathogen Mycobacterium tuberculosis, could be an effective host directed therapy for the disease. In this study, curdlan was conjugated to poly(lactic-co-glycolic acid) (PLGA) to produce immunotherapeutic NPs. Various physicochemical characterizations were used to evaluate the curdlan-PLGA copolymer and the NPs. Molecular dynamics and simulation studies were used to characterize the interaction between curdlan, on the polymer and on NPs, with the Dectin-1 macrophage receptor. NPs with varying curdlan densities were evaluated for their effects on the production of pro- and anti-inflammatory cytokines in M. tuberculosis infected RAW264.7 macrophages. The killing efficacy of the NPs against intracellular M. tuberculosis was assessed. Physicochemical characterization of the curdlan-PLGA copolymer and NPs indicated successful formation of curdlan-PLGA copolymer and NPs of varying curdlan density (0-8% w/w) had sizes between 330 and 453 nm. Modelling studies showed curdlan to have a strong affinity for Dectin-1. Cytotoxicity assays showed the NPs to be non-toxic over 72 h. The proinflammatory cytokine TNF-α was found to be significantly upregulated by the NPs. The NPs reduced intracellular M. tuberculosis burden over 72 h. These NPs are a promising host directed therapy for intracellular eradication of M. tuberculosis.

Keywords: Host-directed therapy and nanoparticles; Immunotherapy and tuberculosis; PLGA immunotherapeutic nanoparticles; PLGA nanoparticles and tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Carriers / chemistry
  • Glycols
  • Lactic Acid / chemistry
  • Mycobacterium tuberculosis*
  • Nanoparticles* / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • beta-Glucans


  • Drug Carriers
  • Glycols
  • beta-Glucans
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • curdlan