title: Amphipathic homopolymers for siRNA delivery: probing impact of bifunctional polymer composition on transfection.
abstract: In this study, we systematically explore the influence of the lipophilic group on the siRNA transfection properties of the polycationic-based delivery vectors. For this, a novel and modular synthetic strategy was developed for the preparation of polymers carrying a cationic site and a lipophilic group at each polymer repeat unit. These bifunctional polymers could form a complex with siRNA and deliver it to human colon carcinoma cells (HT-29-luc). In general, transfection capability increased with an increase in the chain length of the lipophilic moiety. The best transfection agent, a polymer containing ammonium groups and pentyl side chains, exhibited lower toxicity and higher transfection efficiency than branched and linear polyethylenimines (PEI). Moreover, as opposed to PEI, the transfection efficiency of polymer/siRNA complexes remained unchanged in the presence of bafilomycin A1, a proton pump inhibitor, suggesting that the present system did not rely on the "proton sponge" effect for siRNA delivery.
authors.affiliation: Department of Materials and §Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH-Zürich , CH-8093, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Buerkli
authors.forename: Soo Hyeon
authors.initials: SH
authors.lastname: Lee
authors.forename: Elena
authors.initials: E
authors.lastname: Moroz
authors.forename: Mihaiela C
authors.initials: MC
authors.lastname: Stuparu
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
authors.forename: Anzar
authors.initials: A
authors.lastname: Khan
mesh_terms: D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018942:Macrolides / Q000494:pharmacology; D015394:Molecular Structure; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D014162:Transfection / Q000379:methods*
chemical_list: D004337:Drug Carriers; D018942:Macrolides; D034741:RNA, Small Interfering; C040929:bafilomycin A1; D011094:Polyethyleneimine