Liposome-polyethylenimine complexes (DPPC-PEI lipopolyplexes) for therapeutic siRNA delivery in vivo

Publication date: Available online 20 August 2016 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Alexander Ewe, Omkar Panchal, Shashank Reddy Pinnapireddy, Udo Bakowsky, Susanne Przybylski, Achim Temme, Achim Aigner Therapeutic applications of RNA interference (RNAi) require efficient siRNA delivery strategies in vivo. Combining lipid-based carriers with polymeric nanoparticles offers the favourable 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 analysed 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 a~65% survivin knockdown in the tumors. We thus demonstrate that PEI-based lipopolyplexes represent an efficient platform for therapeutic u...

Source: Nanomedicine: Nanotechnology, Biology and Medicine - August 20, 2016 Category: Nanotechnology Source Type: research