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

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.