title: Neutrophil targeted nano-drug delivery system for chronic obstructive lung diseases.
abstract: The success of drug delivery to target airway cell(s) remains a significant challenge due to the limited ability of nanoparticle (NP) systems to circumvent protective airway-defense mechanisms. The size, density, surface and physical-chemical properties of nanoparticles are the key features that determine their ability to navigate across the airway-barrier. We evaluated here the efficacy of a PEGylated immuno-conjugated PLGA-nanoparticle (PINP) to overcome this challenge and selectively deliver drug to specific inflammatory cells (neutrophils). We first characterized the size, shape, surface-properties and neutrophil targeting using dynamic laser scattering, transmission electron microscopy and flow cytometry. Next, we assessed the efficacy of neutrophil-targeted PINPs in transporting through the airway followed by specific binding and release of drug to neutrophils. Finally, our results demonstrate the efficacy of PINP mediated non-steroidal anti-inflammatory drug-(ibuprofen) delivery to neutrophils in murine models of obstructive lung diseases, based on its ability to control neutrophilic-inflammation and resulting lung disease.
authors.affiliation: Department of Pediatric Respiratory Science, The Johns Hopkins University School of Medicine, Baltimore, MD; College of Medicine, Central Michigan University, Mt Pleasant, MI. Electronic address: neeraj.vij@cmich.edu.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Vij
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD; Genentech, 1 DNA Way, San Francisco, CA.
authors.forename: Taehong
authors.initials: T
authors.lastname: Min
authors.affiliation: Department of Pediatric Respiratory Science, The Johns Hopkins University School of Medicine, Baltimore, MD; College of Medicine, Central Michigan University, Mt Pleasant, MI.
authors.forename: Manish
authors.initials: M
authors.lastname: Bodas
authors.affiliation: Department of Pediatric Respiratory Science, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Aakruti
authors.initials: A
authors.lastname: Gorde
authors.affiliation: Department of Chemistry, State University of New York, Buffalo, NY.
authors.forename: Indrajit
authors.initials: I
authors.lastname: Roy
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D019344:Lactic Acid; D051379:Mice; D053758:Nanoparticles; D009504:Neutrophils / Q000187:drug effects*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: COPD; Cystic fibrosis; Drug delivery; Emphysema; Lungs; NFκB; Nanoparticle; Neutrophils