Chitosan/siRNA Nanoparticles Encapsulated in PLGA Nanofibers for siRNA Delivery
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- 作者：Menglin Chen ; Shan Gao ; Mingdong Dong ; Jie Song ; Chuanxu Yang ; Kenneth Alan Howard ; J酶rgen Kjems ; Flemming Besenbacher
- 刊名：ACS Nano
- 出版年：2012
- 出版时间：June 26, 2012
- 年：2012
- 卷：6
- 期：6
- 页码：4835-4844
- 全文大小：533K
- 年卷期：v.6,no.6(June 26, 2012)
- ISSN：1936-086X
文摘
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 Tg 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.