title: Chitosan/siRNA nanoparticles encapsulated in PLGA nanofibers for siRNA delivery.
abstract: Composite nanofibers of biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) encapsulating chitosan/siRNA nanoparticles (NPs) were prepared by electrospinning. Acidic/alkaline hydrolysis and a bulk/surface degradation mechanism were investigated in order to achieve an optimized release profile for prolonged and efficient gene silencing. Thermo-controlled AFM in situ imaging not only revealed the integrity of the encapsulated chitosan/siRNA polyplex but also shed light on the decreasing T(g) of PLGA on the fiber surfaces during release. A triphasic release profile based on bulk erosion was obtained at pH 7.4, while a triphasic release profile involving both surface erosion and bulk erosion was obtained at pH 5.5. A short alkaline pretreatment provided a homogeneous hydrolysis and consequently a nearly zero-order release profile. The interesting release profile was further investigated for siRNA transfection, where the encapsulated chitosan/siRNA NPs exhibited up to 50% EGFP gene silencing activity after 48 h post-transfection on H1299 cells.
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark. menglin@inano.au.dk
authors.forename: Menglin
authors.initials: M
authors.lastname: Chen
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Mingdong
authors.initials: M
authors.lastname: Dong
authors.forename: Jie
authors.initials: J
authors.lastname: Song
authors.forename: Chuanxu
authors.initials: C
authors.lastname: Yang
authors.forename: Kenneth Alan
authors.initials: KA
authors.lastname: Howard
authors.forename: Jørgen
authors.initials: J
authors.lastname: Kjems
authors.forename: Flemming
authors.initials: F
authors.lastname: Besenbacher
mesh_terms: D000818:Animals; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis*; D004058:Diffusion; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D020099:Coated Materials, Biocompatible; D053769:Nanocapsules; D034741:RNA, Small Interfering; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid