title: New gene delivery system based on oligochitosan and solid lipid nanoparticles: 'in vitro' and 'in vivo' evaluation.
abstract: In the present work, we evaluated the potential utility for gene delivery of three oligochitosans (OligoCh) that differs in the M(n) (OligoChA: 6.1 kDa, OligoChB: 11.5 kDa, and OligoChC: 13.7 kDa), with deacetylation degree of 85%. OligoCh were complexed directly with the pCMS-EGFP plasmid to form OligoCh-DNA carriers. Taking into account the features and benefits of both Ch and SLNs, we also combined the OligoCh with SLNs. The three OligoCh presented a great ability to condense and protect the DNA. The OligoCh of highest M(n) (OligoChC) complexed with SLNs at a OligoChC:DNA:SLN ratio 2.5:1:5 induced the highest transfection level in HEK-293 cells at day 3; being transfection 2-fold higher at day 7. After the intravenous administration to mice, OligoChC-DNA and OligoChC-DNA-SLN vectors were able to induce the expression of EGFP in the spleen, lung and liver, which was maintained for at least 7 days. In spite of the difference in the "in vitro" transfection levels between both vectors, no difference was detected in transfection after "in vivo" administration. Moreover, the OligoChC improved the "in vivo" transfection efficacy of the DNA-SLN vector. This work shows the potential utility of the combination of SLNs and OligoCh for the development of new non-viral vectors for gene therapy.
authors: Pharmacokinetics, Nanotechnology and Gene Therapy Group, Pharmacy and Pharmaceutical Technology Laboratory, Pharmacy Faculty, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Spain.
authors: Diego
authors: D
authors: Delgado
authors: Ana
authors: A
authors: del Pozo-Rodríguez
authors: M
authors: M
authors: Angeles Solinís
authors: Artur
authors: A
authors: Bartkowiak
authors: Alicia
authors: A
authors: Rodríguez-Gascón
mesh_terms: D000818:Animals; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D004075:Diglycerides / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009844:Oligosaccharides; D010957:Plasmids; D011136:Polysorbates / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013154:Spleen / Q000378:metabolism; D014162:Transfection / Q000379:methods*
chemical_list: D004075:Diglycerides; D005229:Fatty Acids, Monounsaturated; D009844:Oligosaccharides; D011136:Polysorbates; D000644:Quaternary Ammonium Compounds; C485184:enhanced green fluorescent protein; C493484:oligochitosan; D002686:Chitin; D049452:Green Fluorescent Proteins; D004247:DNA; D048271:Chitosan; C009032:precirol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
keywords: Ch; EGFP; Gene therapy; MM; Non-viral vector; OligoCh; Oligochitosan; RT; SLN; Solid lipid nanoparticles; chitosan; green fluorescent protein; molar mass; oligochitosan; room temperature; solid lipid nanoparticle; ‘In vivo’ transfection