Polymeric nanoparticles for pulmonary protein and DNA delivery

Jyothi U. Menon, Priya Ravikumar, Amruta Pise, Dipendra Gyawali, Connie C W Hsia, Kytai T. Nguyen

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

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 <300 nm 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 5 days. 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 10 days while increasing YFP expression was observed for at least 7 days for both NPs. The overall results support both PLGA and gelatin NPs as promising carriers for pulmonary protein/DNA delivery.

Original languageEnglish (US)
Pages (from-to)2643-2652
Number of pages10
JournalActa Biomaterialia
Volume10
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • DNA
  • Nanoparticles
  • Nebulization
  • Protein
  • Pulmonary

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

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