title: Self-assembled biodegradable amphiphilic PEG-PCL-lPEI triblock copolymers at the borderline between micelles and nanoparticles designed for drug and gene delivery.
abstract: Amphiphilic PEG-PCL-PEI triblock copolymers self-assemble into nano-scaled, positively charged, multifunctional carriers, suitable for drug and gene delivery. A set of block copolymers with varying hydrophilic/hydrophobic ratio (systematically altered at the borderline of micelle and particle forming polymers) was synthesized, characterized and assembled into carriers. A detailed structural characterization in the liquid state of these assemblies was carried out: carrier size was determined using dynamic light scattering, cryogenic scanning electron microscopy and atomic force microscopy. Nuclear magnetic resonance analyses elucidated carrier's core-shell structure. ζ-potential and thickness of the hydrophilic outer polymer shell were determined by laser Doppler anemometry. Subsequently the impact of carrier's structure on its features (stability and toxicity) was investigated. Polymers hydrophilic in nature formed small (<40 nm) micelle-like carriers, whilst hydrophobic polymers aggregated to larger particle-like assemblies (>100 nm). Monitoring carrier size as a function of initial polymer concentration clarified different assembly mechanisms. Shell thickness, colloidal stability and toxicity were found to depend on the length of the hydrophilic polymer block. Due to controllable size, charge, stability and toxicity, this class of novel carriers is a promising candidate for prospective co-delivery of drugs and nucleic acids.
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps-Universitaet of Marburg, Ketzerbach 63, 35037 Marburg, Germany.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Endres
authors.forename: Moritz
authors.initials: M
authors.lastname: Beck-Broichsitter
authors.forename: Olga
authors.initials: O
authors.lastname: Samsonova
authors.forename: Thomas
authors.initials: T
authors.lastname: Renette
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Kissel
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D018014:Gene Transfer Techniques; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011091:Polyesters / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D013501:Surface-Active Agents / Q000737:chemistry* / Q000633:toxicity
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D013501:Surface-Active Agents; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); C016240:polycaprolactone; D011092:Polyethylene Glycols; D011094:Polyethyleneimine