PMID- 22800573 OWN - NLM STAT- MEDLINE DCOM- 20130131 LR - 20181201 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 162 IP - 2 DP - 2012 Sep 10 TI - Prolonged gene silencing by siRNA/chitosan-g-deoxycholic acid polyplexes loaded within biodegradable polymer nanoparticles. PG - 407-13 LID - 10.1016/j.jconrel.2012.07.006 [doi] AB - Recently, small interfering RNA (siRNA) has received much attention for therapeutic applications; however, low transfection efficiency and intrinsic instability limit effective gene silencing. Here we show a new approach based on the incorporation of siRNA/polyelectrolyte complexes into biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles to stabilize siRNA within a hydrophobic solid matrix for prolonged gene silencing. To solubilize siRNA in organic media, chitosan oligosaccharides grafted with deoxycholic acids are synthesized and complexed with siRNA, generating a self-assembled polyelectrolyte complex of 123.9 +/- 56.8 nm in diameter. The complex is mixed with PLGA solution and emulsified in water to prepare siRNA-loaded PLGA nanoparticles having a diameter of about 230 nm. The excellent structural stability of the prepared nanoparticles leads to efficient cellular uptake followed by effective gene silencing even in the presence of serum proteins. These results suggest that the encapsulation of siRNA into biodegradable polymer matrix can be an effective means of improving the structural stability of siRNA for prolonged therapeutic efficacy. CI - Copyright (c) 2012 Elsevier B.V. All rights reserved. FAU - Lee, Jeong Yu AU - Lee JY AD - Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea. FAU - Lee, Soo Hyeon AU - Lee SH FAU - Oh, Mi Hwa AU - Oh MH FAU - Kim, Jee Seon AU - Kim JS FAU - Park, Tae Gwan AU - Park TG FAU - Nam, Yoon Sung AU - Nam YS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120716 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (Oligosaccharides) RN - 0 (RNA, Small Interfering) RN - 005990WHZZ (Deoxycholic Acid) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) RN - 9012-76-4 (Chitosan) SB - IM MH - Biological Transport MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Chitosan/*administration & dosage/chemistry MH - Deoxycholic Acid/*administration & dosage/chemistry MH - Gene Silencing MH - Green Fluorescent Proteins/genetics MH - Humans MH - Lactic Acid/*administration & dosage/chemistry MH - Nanoparticles/administration & dosage/chemistry MH - Oligosaccharides/*administration & dosage/chemistry MH - Polyglycolic Acid/*administration & dosage/chemistry MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - RNA, Small Interfering/*administration & dosage/genetics MH - Transfection EDAT- 2012/07/18 06:00 MHDA- 2013/02/01 06:00 CRDT- 2012/07/18 06:00 PHST- 2012/03/28 00:00 [received] PHST- 2012/06/14 00:00 [revised] PHST- 2012/07/04 00:00 [accepted] PHST- 2012/07/18 06:00 [entrez] PHST- 2012/07/18 06:00 [pubmed] PHST- 2013/02/01 06:00 [medline] AID - S0168-3659(12)00546-9 [pii] AID - 10.1016/j.jconrel.2012.07.006 [doi] PST - ppublish SO - J Control Release. 2012 Sep 10;162(2):407-13. doi: 10.1016/j.jconrel.2012.07.006. Epub 2012 Jul 16.