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

Gaspar, Diana P.; Vital, Joana; Leiva, María C.; Gonçalves, Lídia M. D.; Taboada, Pablo; Remuñán-López, Carmen; Vítor, Jorge M. B.; Almeida, António J.

http://hdl.handle.net/10451/57469

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Authors

Gaspar, Diana P.

Vital, Joana

Leiva, María C.

Gonçalves, Lídia M. D.

Taboada, Pablo

Remuñán-López, Carmen

Vítor, Jorge M. B.

Almeida, António J.

Abstract(s)

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.