Research Article For reprint orders, please contact: reprints@futuremedicine.com Transfection of pulmonary cells by stable pDNA-polycationic hybrid nanostructured particles Diana P Gaspar 1,2 , Joana Vital 3 , Mar´ ıa C Leiva 4,5,6 , L´ ıdia MD Gonc ¸alves 1 , Pablo Taboada 7 , Carmen Remu ˜ n´ an-L ´ opez 2 , Jorge V´ ıtor 8 & Ant ´ onio J Almeida* ,1 1 Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal 2 Nanobiofar Group, Department of Pharmacology, Pharmacy & Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain 3 CQBFarma,1500-592 Lisbon, Portugal 4 Institute of Biopatology & Regenerative Medicine (IBIMER), Biomedical Research Center (CIBM), 18071 Granada, Spain 5 Department of Anatomy & Embryology, University of Granada, 18071 Granada, Spain 6 Biosanitary Institute of Granada (ibs.GRANADA), SAS - University of Granada, 18071 Granada, Spain 7 Colloids & Polymers Physics Group, Department of Condensed Matter Physics, Faculty of Physics, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain 8 Department of Biochemistry & Human Biology, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal *Author for correspondence: Tel.: +351 217 946 400; aalmeida@ff.ulisboa.pt Aim: Cationically modifed solid lipid nanoparticles (SLN) were investigated as plasmid DNA (pDNA) carri- ers and transfection agents for the pulmonary route. Materials & methods: pDNA-loaded SLN were pro- duced using glyceryl dibehenate or tristearate as matrix lipids and chitosan as surface charge modifer, 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 confrmed 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. Graphical abstract: CS layer pDNA layer Spray- drying Redispersability into nanoparticles pDNA integrity Transfection studies In vitro viability studies Nanomedicine (Lond.) (Epub ahead of print) ISSN 1743-5889 10.2217/nnm-2018-0270 C  2019 Future Medicine Ltd