title: Polymeric nanoparticles for pulmonary protein and DNA delivery.
abstract: Polymeric nanoparticles (NPs) are promising carriers of biological agents to the lung due to advantages including biocompatibility, ease of surface modification, localized action and reduced systemic toxicity. However, there have been no studies extensively characterizing and comparing the behavior of polymeric NPs for pulmonary protein/DNA delivery both in vitro and in vitro. We screened six polymeric NPs: gelatin, chitosan, alginate, poly(lactic-co-glycolic) acid (PLGA), PLGA-chitosan and PLGA-poly(ethylene glycol) (PEG), for inhalational protein/DNA delivery. All NPs except PLGA-PEG and alginate were <300nm in size with a bi-phasic core compound release profile. Gelatin, PLGA NPs and PLGA-PEG NPs remained stable in deionized water, serum, saline and simulated lung fluid (Gamble's solution) over 5days. PLGA-based NPs and natural polymer NPs exhibited the highest cytocompatibility and dose-dependent in vitro uptake, respectively, by human alveolar type-1 epithelial cells. Based on these profiles, gelatin and PLGA NPs were used to encapsulate plasmid DNA encoding yellow fluorescent protein (YFP) or rhodamine-conjugated erythropoietin (EPO) for inhalational delivery to rats. Following a single inhalation, widespread pulmonary EPO distribution persisted for up to 10days while increasing YFP expression was observed for at least 7days for both NPs. The overall results support both PLGA and gelatin NPs as promising carriers for pulmonary protein/DNA delivery.
authors: Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, USA; Graduate Biomedical Engineering Program, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors: Jyothi U
authors: JU
authors: Menon
authors: Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors: Priya
authors: P
authors: Ravikumar
authors: Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, USA; Graduate Biomedical Engineering Program, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors: Amruta
authors: A
authors: Pise
authors: Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, USA; Graduate Biomedical Engineering Program, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors: Dipendra
authors: D
authors: Gyawali
authors: Graduate Biomedical Engineering Program, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. Electronic address: Connie.Hsia@utsouthwestern.edu.
authors: Connie C W
authors: CC
authors: Hsia
authors: Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, USA; Graduate Biomedical Engineering Program, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. Electronic address: knguyen@uta.edu.
authors: Kytai T
authors: KT
authors: Nguyen
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D008168:Lung / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage*; D011108:Polymers / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011108:Polymers; D004247:DNA
keywords: DNA; Nanoparticles; Nebulization; Protein; Pulmonary