title: Hydrodynamic delivery of chitosan-folate-DNA nanoparticles in rats with adjuvant-induced arthritis.
abstract: 50 kDa chitosan was conjugated with folate, a specific tissue-targeting ligand. Nanoparticles such as chitosan-DNA and folate-chitosan-DNA were prepared by coacervation process. The hydrodynamic intravenous injection of nanoparticles was performed in the right posterior paw in normal and arthritic rats. Our results demonstrated that the fluorescence intensity of DsRed detected was 5 to 12 times more in the right soleus muscle and in the right gastro muscle than other tissue sections. β-galactosidase gene expression with X-gal substrate and folate-chitosan-plasmid nanoparticles showed best coloration in the soleus muscle. Treated arthritic animals also showed a significant decrease in paw swelling and IL-1β and PGE₂ concentration in serum compared to untreated rats. This study demonstrated that a nonviral gene therapeutic approach using hydrodynamic delivery could help transfect more efficiently folate-chitosan-DNA nanoparticles in vitro/in vivo and could decrease inflammation in arthritic rats.
authors.affiliation: Orthopaedics Research Laboratory, Research Centre, Sacré-Coeur Hospital, University of Montreal, 5400 West Gouin Boulevard, Montreal, QC, Canada. qin.shi@umontreal.ca
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
authors.forename: Huijie
authors.initials: H
authors.lastname: Wang
authors.forename: Covi
authors.initials: C
authors.lastname: Tran
authors.forename: Xingping
authors.initials: X
authors.lastname: Qiu
authors.forename: Françoise M
authors.initials: FM
authors.lastname: Winnik
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
authors.forename: Kerong
authors.initials: K
authors.lastname: Dai
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benderdour
authors.forename: Julio C
authors.initials: JC
authors.lastname: Fernandes
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D048271:Chitosan / Q000008:administration & dosage*; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006651:Histocytochemistry; D006801:Humans; D007275:Injections, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D013643:Tarsus, Animal / Q000473:pathology; D014018:Tissue Distribution; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D058726:Nanoconjugates; D004247:DNA; D005620:Freund's Adjuvant; D048271:Chitosan; D005492:Folic Acid; D001616:beta-Galactosidase; D015232:Dinoprostone