Transfection of pulmonary cells by stable pDNA-polycationic hybrid nanostructured particles

Nanomedicine (Lond). 2019 Feb;14(4):407-429. doi: 10.2217/nnm-2018-0270. Epub 2019 Jan 30.

Abstract

Aim: Cationically modified solid lipid nanoparticles (SLN) were investigated as plasmid DNA (pDNA) carriers and transfection agents for the pulmonary route.

Materials & methods: pDNA-loaded SLN were produced using glyceryl dibehenate or tristearate as matrix lipids and chitosan as surface charge modifier, and encapsulated by spray-drying in mannitol and trehalose microspheres.

Results: Nanoparticles of 200 nm, and zeta potential around +15 mV were produced. Electrophorectic analysis confirmed plasmid stability and integrity. The pDNA-loaded SLN were able to transfect the Calu-3 and A549 pulmonary cell lines, while showing low cytotoxicity. Microencapsulation of SLN yielded dry powders suitable for inhalation that protected pDNA from degradation.

Conclusion: Microencapsulated SLN are a promising safe and effective carrier system for pulmonary gene delivery following pulmonary administration.

Keywords: chitosan; gene delivery; inhalation; microencapsulation; plasmid; solid lipid nanoparticles; spray-drying.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chitosan / chemistry
  • Drug Carriers / chemistry
  • Gene Transfer Techniques
  • Lipids / chemistry
  • Nanoparticles / chemistry*
  • Plasmids / genetics
  • Transfection / methods

Substances

  • Drug Carriers
  • Lipids
  • Chitosan