title: Polyion complex micelles composed of pegylated polyasparthydrazide derivatives for siRNA delivery to the brain.
abstract: In order to achieve efficient siRNA delivery to the brain, we designed a novel polyion complex (PIC) micelles composed of rabies virus glycoprotein (RVG) peptide tagged PEGylated polyasparthydrazide (PAHy) derivatives. The synthesized derivatives were characterized using (1)H NMR. The PIC micelles were formed by electrostatic attraction between the polymer and siRNA. Then the micelles were decorated with RVG using PEG as a linker. The physiochemical properties of micelles, such as gel retardation assay, zeta potential, particle size, morphology and serum stability, were investigated. Moreover, the cytotoxicity, cellular uptake, gene silencing efficiency and in vivo distribution of micelles were also evaluated systematically. Compared with unmodified micelles, RVG-modified micelles can be more easily internalized by the neuro2a cells and efficiently silence gene expression. In vivo animal experiments further confirmed that RVG modified micelles had brain targeting ability. These results demonstrated that RVG-modified micelles were promising carriers for siRNA delivery to the brain.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang 110122, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Huo
authors.affiliation: School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yikun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jinghai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110004, China.
authors.forename: Zhan-You
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: jiangtongyingspu@163.com.
authors.forename: Tongying
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: silingwang@syphu.edu.cn.
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D007477:Ions; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008823:Micelles; D009447:Neuroblastoma / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D006023:Glycoproteins; D006834:Hydrazines; D007477:Ions; D008823:Micelles; D010446:Peptide Fragments; D011108:Polymers; D034741:RNA, Small Interfering; D014764:Viral Proteins; C583075:rabies virus glycoprotein peptide; D011092:Polyethylene Glycols
keywords: Brain targeting; Polyasparthydrazide; Polyion complex micelles; RVG peptide; siRNA delivery