Physicochemical and Biological Evaluation of siRNA Polyplexes Based on PEGylated Poly(amido amine)s

Abstract

PurposeUse of RNA interference as novel therapeutic strategy is hampered by inefficient delivery of its mediator, siRNA, to target cells. Cationic polymers have been thoroughly investigated for this purpose but often display unfavorable characteristics for systemic administration, such as interactions with serum and/or toxicity.MethodsWe report the synthesis of a new PEGylated polymer based on biodegradable poly(amido amine)s with disulfide linkages in the backbone. Various amounts of PEGylated polymers were mixed with their unPEGylated counterparts prior to polyplex formation to alter PEG content in the final complex.ResultsPEGylation effectively decreased polyplex surface charge, salt- or serum-induced aggregation and interaction with erythrocytes. Increasing amount of PEG in formulation also reduced its stability against heparin displacement, cellular uptake and subsequent silencing efficiency. Yet, for polyplexes with high PEG content, significant gene silencing efficacy was found, which was combined with almost no toxicity.ConclusionsPEGylated poly(amido amine)s are promising carriers for systemic siRNA delivery in vivo.

Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: Effect of reversing primary and secondary face modifications

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Therapeutic efficiency of folated poly(ethylene glycol)-chitosan-graft-polyethylenimine-Pdcd4 complexes in H-ras12V mice with liver cancer

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Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery

“…Two parallel transfection series -one for the qualitative analysis of transfection efficiency using fluorescence microscopy (FM) and the other for the quantitative analysis using flow cytometry (FCM) -were established. MCF-7 cells were seeded in six-well plates at a density of 1 …”

“…1 Carriers for gene delivery can be divided into two classes: viral and nonviral. Viral carriers are modified viruses that can deliver exogenous genes to the cells.…”