Hemocompatibility Assessment of two siRNA Nanocarrier Formulations

Afrouz Yousefi, Marianne Lauwers, Reka Nemes, Thijs van Holten, Negar Babae, Mark Roest, Gert Storm, Raymond Schiffelers, Enrico Mastrobattista*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose Since the discovery of RNAi and its therapeutic potential, carrier systems have been developed to deliver small RNAs (particularly siRNA) for modulation of gene expression at the post-transcriptional level. An important factor determining the fate and usability of these systems in vivo is interaction with blood components, blood cells, and the immune system. In this study, a lipid-based and a polymer-based carrier system containing siRNA have been investigated in vitro in terms of their hemocompatibility. Methods The nanocomplexes studied were Angiplex, a targeted lipid-based system, and pHPMA-MPPM polyplex, a formulation based on a cationic polymer. siVEGFR-2 was encapsulated in both carriers and activation of platelets, coagulation, and complement cascade as well as induction of platelet aggregation were evaluated in vitro. Results Both systems had been shown before to cause significant silencing in vitro. Our findings indicated that pHPMA-MPPM polyplex triggered high platelet activation and aggregation although it did not stimulate coagulation substantially. Angiplex, on the other hand, provoked insignificant activation and aggregation of platelets and activated coagulation minimally. Complement system activation by Angiplex was in general low but stronger than pHPMA-MPPM polyplex. Conclusions Taken together, these in vitro assays may help the selection of suitable carriers for systemic delivery of siRNA in early preclinical investigations and reduce the use of laboratory animals significantly.

Original languageEnglish
Pages (from-to)3127-3135
Number of pages9
JournalPharmaceutical Research
Volume31
Issue number11
DOIs
Publication statusPublished - 20 May 2014

Fingerprint

Dive into the research topics of 'Hemocompatibility Assessment of two siRNA Nanocarrier Formulations'. Together they form a unique fingerprint.

Cite this