title: Biophysical characterization of hyper-branched polyethylenimine-graft-polycaprolactone-block-mono-methoxyl-poly(ethylene glycol) copolymers (hy-PEI-PCL-mPEG) for siRNA delivery.
abstract: A library of mono-methoxyl-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) modified hyperbranched PEI copolymers (hy-PEI-PCL-mPEG) was synthesized to establish structure function relationships for siRNA delivery. These amphiphilic block-copolymers were thought to provide improved colloidal stability and endosomal escape of polyplexes containing siRNA. The influence of the mPEG chain length, PCL segment length, hy-PEI molecular weight and the graft density on their biophysical properties was investigated. In particular, buffer capacity, complex formation constants, gene condensation, polyplex stability, polyplex size and zeta-potential were measured. It was found that longer mPEG chains, longer PCL segments and higher graft density beneficially affected the stability and formation of polyplexes and reduced the zeta-potential of siRNA polyplexes. Significant siRNA mediated knockdown was observed for hy-PEI25k-(PCL900-mPEG2k)(1) at N/P 20 and 30, implying that the PCL hydrophobic segment played a very important role in siRNA transfection. These gene delivery systems merit further investigation under in vivo conditions.
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps-Universität Marburg, Ketzerbach 63, D-35037 Marburg, Germany.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Olga
authors.initials: O
authors.lastname: Samsonova
authors.forename: Brian
authors.initials: B
authors.lastname: Sproat
authors.forename: Olivia
authors.initials: O
authors.lastname: Merkel
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
mesh_terms: D055592:Biophysical Phenomena; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014162:Transfection
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D034741:RNA, Small Interfering; C016240:polycaprolactone; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; C028210:monomethoxypolyethylene glycol