title: Multimodal nanoparticles that provide immunomodulation and intracellular drug delivery for infectious diseases.
abstract: Infectious diseases are a worldwide health concern. For some infections, a common feature is the intracellular residence of the pathogen and evasion of the host immune response. In the case of tuberculosis (TB), Mycobacterium tuberculosis evades clearance within macrophages through suppression of intracellular reactive oxygen and nitrogen species (ROS/RNS) and pro-inflammatory cytokines. We propose new nanoparticle designs for infectious diseases, functionalized with ligands able to modulate the cellular immune response and concurrently deliver drug. We have designed 1,3-β-glucan functionalized chitosan shell, poly(lactide)co-glycolide core nanoparticles to stimulate ROS/RNS, pro-inflammatory cytokine secretion, and delivery of rifampicin inside human alveolar like macrophages (ALM). Nanoparticles significantly enhanced ALM secretion of IL-12p70 (2.9-fold), TNF-α (16-fold) and INF-γ (23-fold) compared to controls over 24h, and doubled ROS/RNS generation over 6h. Nanoparticles could deliver 4-fold greater rifampicin into ALM compared to rifampicin solution. These results provide proof-of-concept of multimodal nanoparticles and support their further development.
  
  
  BACKGROUND
  In this paper, a new nanoparticle design is proposed to address hard to treat infectious diseases such as TB, through the use of nanoparticles functionalized with ligands that are able to concurrently modulate the cellular immune response and deliver a drug. The authors have designed 1,3-β-glucan functionalized chitosan shell - poly(lactide)co-glycolide core nanoparticles to stimulate reactive oxygen and nitrogen species production, pro-inflammatory cytokine secretion, and delivery of rifampicin inside human alveolar-like macrophages.
authors: School of Pharmacy, University of Zimbabwe, Harare, Zimbabwe.
authors: Admire
authors: A
authors: Dube
authors: Department of Medicine, University at Buffalo, Buffalo NY, USA.
authors: Jessica L
authors: JL
authors: Reynolds
authors: The Institute for Lasers, Photonics and Biophotonics, University at Buffalo, Buffalo, NY, USA.
authors: Wing-Cheung
authors: WC
authors: Law
authors: School of Pharmacy, University of Zimbabwe, Harare, Zimbabwe.
authors: Charles C
authors: CC
authors: Maponga
authors: The Institute for Lasers, Photonics and Biophotonics, University at Buffalo, Buffalo, NY, USA; Department of Chemistry, Korea University, Seoul, South Korea. Electronic address: pnprasad@buffalo.edu.
authors: Paras N
authors: PN
authors: Prasad
authors: Translational Pharmacology Research Core, New York State Center of Excellence in Bioinformatics and Life Sciences; School of Pharmacy and Pharmaceutical Sciences; University at Buffalo, Buffalo, NY, USA. Electronic address: emorse@buffalo.edu.
authors: Gene D
authors: GD
authors: Morse
mesh_terms: D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D009000:Monocytes; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan
keywords: 1,3-β-glucan; Infectious diseases; Multimodal nanoparticles; Mycobacterium tuberculosis; PLGA