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 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.
| Original language | English |
|---|---|
| Journal | A C S Nano |
| Volume | 6 |
| Issue | 6 |
| Pages (from-to) | 4835-4844 |
| Number of pages | 10 |
| ISSN | 1936-0851 |
| DOIs | |
| Publication status | Published - 26 Jun 2012 |
Keywords
- nanofibers
- chitosan
- siRNA
- electrospinning
- release
- gene silencing