title: Liposome-polyethylenimine complexes (DPPC-PEI lipopolyplexes) for therapeutic siRNA delivery in vivo.
abstract: Therapeutic applications of RNA interference (RNAi) require efficient siRNA delivery strategies in vivo. Combining lipid-based carriers with polymeric nanoparticles offers the favorable properties of both systems. This is the first study to explore polyethylenimine-based lipopolyplexes comprising a low-molecular weight PEI and the phospholipid DPPC for therapeutic siRNA use. Lipopolyplex structures are analyzed by electron microscopy. Biological efficacies are demonstrated in vitro by cellular uptake, knockdown of the target oncogene survivin, and concomitant cell growth inhibition. Upon systemic administration in tumor-bearing mice, here performed by intraperitoneal (i.p.) injection, radioactive biodistribution assays show lipopolyplex-mediated delivery of intact siRNAs. Absence of blood serum parameter alterations, erythrocyte aggregation or immunostimulation, and the observation of animal well-being and stable body weight confirm biocompatibility. Exploring therapeutic efficacies in a preclinical model, a considerable inhibition of prostate carcinoma xenograft growth is achieved, paralleled by an ~65% survivin knockdown in the tumors. We, thus, demonstrate that PEI-based lipopolyplexes represent an efficient platform for therapeutic use of small RNAs.
authors.affiliation: Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ewe
authors.affiliation: Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Germany.
authors.forename: Omkar
authors.initials: O
authors.lastname: Panchal
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Philipps-University Marburg, Germany.
authors.forename: Shashank Reddy
authors.initials: SR
authors.lastname: Pinnapireddy
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Philipps-University Marburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Bakowsky
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Przybylski
authors.affiliation: Department of Neurosurgery, University Hospital Carl Gustav Carus, Technical University, Dresden, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Temme
authors.affiliation: Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Germany. Electronic address: achim.aigner@medizin.uni-leipzig.de.
authors.forename: Achim
authors.initials: A
authors.lastname: Aigner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011094:Polyethyleneimine / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000628:therapy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D034741:RNA, Small Interfering; D011094:Polyethyleneimine
keywords: Lipopolyplex; Liposome; Polyethlyenimine; RNAi; Survivin; siRNA delivery; siRNA therapy