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

Cationically modified solid lipid nanoparticles (SLN) were investigated as plasmid DNA (pDNA) carriers and transfection agents for the pulmonary route. pDNA-loaded SLN were produced using glyceryl dibehenate or tristearate as matrix lipids and chitosan as surface charge modifier, and encapsulated by...

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Bibliographic Details
Published in:Nanomedicine (London, England) England), 2019-02, Vol.14 (4), p.407-429
Main Authors: Gaspar, Diana P, Vital, Joana, Leiva, María C, Gonçalves, Lídia Md, Taboada, Pablo, Remuñán-López, Carmen, Vítor, Jorge, Almeida, António J
Format: Article
Language:English
Subjects:
Biocompatibility
Cytomegalovirus
Deoxyribonucleic acid
DNA
Gene therapy
Genetic engineering
Nanoparticles
Proteins
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Summary:Cationically modified solid lipid nanoparticles (SLN) were investigated as plasmid DNA (pDNA) carriers and transfection agents for the pulmonary route. 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. 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. Microencapsulated SLN are a promising safe and effective carrier system for pulmonary gene delivery following pulmonary administration.
ISSN:1743-5889
1748-6963
DOI:10.2217/nnm-2018-0270