title: Pegylated poly-l-arginine derivatives of chitosan for effective delivery of siRNA.
abstract: For delivery of siRNA, chitosan (CS) was derivatized with poly-l-arginine (PLR) and polyethylene glycol (PEG). The formation of polyplexes with siRNA was confirmed by gel retardation. The PLR-grafted CS formed nanosized particles with siRNA. PLR-grafted CS showed higher cellular delivery efficiency of siRNA than did CS, pegylated CS, PLR, or pegylated PLR. The extent of reduction in the expression of fluorescent proteins was highest following treatment of the cells using PLR derivatives of CS in complexes with specific siRNAs. Cell viability was greater in populations treated with pegylated CS-PLR than in those treated with PLR. Hemolysis of erythrocytes was reduced upon conjugation of PLR with CS. The delivery of siRNAs via pegylated CS-PLR revealed little dependence on serum. Molecular imaging techniques revealed that the intratumoral administration of red fluorescent protein-specific siRNA in complexes with pegylated CS-PLR significantly silenced the expression of red fluorescent proteins in tumor tissues in vivo. These results indicate that pegylated CS-PLR might be useful for in vivo delivery of therapeutic siRNAs.
authors.affiliation: College of Pharmacy, Seoul National University, Sinlim-dong, Gwanak-gu, Seoul, South Korea.
authors.forename: Sang Myoung
authors.initials: SM
authors.lastname: Noh
authors.forename: Myung Ok
authors.initials: MO
authors.lastname: Park
authors.forename: Gayong
authors.initials: G
authors.lastname: Shim
authors.forename: Su Eun
authors.initials: SE
authors.lastname: Han
authors.forename: Han Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Jun Hyuk
authors.initials: JH
authors.lastname: Huh
authors.forename: Myoung Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Jin Joo
authors.initials: JJ
authors.lastname: Choi
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Baek
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy; D051379:Mice; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D011108:Polymers; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D048271:Chitosan; D001120:Arginine