Delivery of pDNA polyplexes to bronchial and alveolar epithelial cells using a mesh nebulizer

Larissa Gomes Dos Reis, Maree Svolos, Lyn M. Moir, Rima Jaber, Norbert Windhab, Paul M. Young, Daniela Traini

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Purpose: In this study, a cell penetrating peptide was used as an uptake enhancer for pDNA delivery to the lungs.

Methods: Polyplexes were prepared between pDNA and CPP. Intracellular delivery of pDNA was assessed in both alveolar (A549) and bronchial (Calu-3) epithelial cells. Aerosol delivery was investigated using a mesh nebulizer.

Results: Efficient intracellular delivery of pDNA occurs in both A549 and Calu-3 cells when delivered as polyplexes. Protection against nucleases and endosomal escape mechanism occurs when pDNA is formulated within the polyplexes. For aerosol delivery, 1% (w/v) mannitol was able to protect naked DNA structure during nebulization with a significant increase in fine particle fraction (particles <5 μm). The structure of polyplexes when delivered via a mesh nebulizer using 1% (w/v) mannitol could partially withstand the shear forces involved in aerosolization. Although some loss in functionality occurred after nebulization, membrane-associated fluorescence was observed in A549 cells. In Calu-3 cells mucus entrapment was a limiting factor for polyplex delivery.

Conclusions: The presence of CPP is essential for efficient intracellular delivery of pDNA. The polyplexes can be delivered to lung epithelial cells using mesh nebulizer. The use of different excipients is essential for further optimization of these delivery systems.

Original languageEnglish
Article number14
Pages (from-to)1-16
Number of pages16
JournalPharmaceutical Research
Volume36
Issue number1
Early online date15 Nov 2018
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

Keywords

  • aerosol
  • cell-penetrating peptide
  • gene delivery
  • lung
  • nebulization

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