Chitosan/siRNA nanoparticles encapsulated in PLGA nanofibers for siRNA delivery

ACS Nano. 2012 Jun 26;6(6):4835-44. doi: 10.1021/nn300106t. Epub 2012 May 31.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coated Materials, Biocompatible / chemical synthesis*
  • Diffusion
  • Lactic Acid / chemistry*
  • Materials Testing
  • Mice
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Particle Size
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / chemistry*
  • Transfection / methods*


  • Coated Materials, Biocompatible
  • Nanocapsules
  • RNA, Small Interfering
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid