title: Proteinase K-containing lipid nanoparticles for therapeutic delivery of siRNA LOR-1284.
abstract: BACKGROUND
  The objective of the present study was to develop an efficient delivery vehicle for siRNA LOR-1284 through incorporation of proteinase K (PrK) as a means of preventing siRNA degradation by serum nucleases. Lipid nanoparticle-PrK-siRNA (LN-PrK-siRNA) complexes were synthesized and characterized.
  
  
  METHODS
  siRNA complexed with PrK and liposomes composed of dimethyldioctadecyl ammonium bromide/cholesterol/Tween 80 (60:35:5 molar ratio) were investigated for down-regulation of R2 mRNA activity in KB human carcinoma cells.
  
  
  RESULTS
  Treatment with LN-PrK-siRNA (30:0.3:1 molar ratio) significantly reduced levels of R2 mRNA compared to siRNA-liposomes without PrK in serum-containing medium. LN-PrK-siRNA complexes showed increased stability in serum and reduced toxicity in KB cells relative to LN-siRNA complexes.
  
  
  CONCLUSIONS
  LN-PrK-siRNA complexes are promising delivery vehicles for siRNA.
authors: Department of Pathology, Graduate School of Medicine, Gyeongsang National University, Jinju, South Korea.
authors: Dong Chul
authors: DC
authors: Kim
authors: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.
authors: Young Ah
authors: YA
authors: Cho
authors: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.
authors: Hong
authors: H
authors: Li
authors: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.
authors: Bryant C
authors: BC
authors: Yung
authors: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A. lee.1339@osu.edu.
authors: Robert J
authors: RJ
authors: Lee
mesh_terms: D000818:Animals; D015536:Down-Regulation; D016503:Drug Delivery Systems; D019286:Endopeptidase K / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007624:KB Cells; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012264:Ribonucleotide Reductases / Q000235:genetics; D014162:Transfection / Q000379:methods
chemical_list: D008081:Liposomes; D034741:RNA, Small Interfering; D012264:Ribonucleotide Reductases; C108427:ribonucleotide reductase R2 subunit; D019286:Endopeptidase K
keywords: Lipid nanoparticle; cancer; proteinase K; ribonucleotide reductase; siRNA