Quo vadis polyplex?

Olivia M Merkel; Thomas Kissel

doi:10.1016/j.jconrel.2014.06.009

Quo vadis polyplex?

J Control Release. 2014 Sep 28:190:415-23. doi: 10.1016/j.jconrel.2014.06.009. Epub 2014 Jun 13.

Authors

Olivia M Merkel¹, Thomas Kissel²

Affiliations

¹ Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA; Department of Oncology, Wayne State University, Detroit, MI 48201, USA. Electronic address: olivia.merkel@wayne.edu.
² Department of Pharmaceutics and Biopharmacy, Philipps-Universität Marburg, Ketzerbach 63, 35037 Marburg, Germany.

PMID: 24933599
DOI: 10.1016/j.jconrel.2014.06.009

Abstract

Polymeric siRNA delivery has been an important field for the Journal of Controlled Release since the early 2000s. With currently about 1600 publications on this topic that can be found in Scopus, we have to ask ourselves why the clinical translation has been so slow. In this review we address the importance of in vivo studies, the problem of biocompatibility of the carrier systems, intracellular entrapment and endosomal release, as well as stability issues in the presence of serum. Most of all, we ask the question: Quo vadis? Where do polymeric carriers go inside the cell and inside the body and how does this affect repeated administration? We show that the gap of knowledge on polymer biodistribution and excretion has not been closed yet and needs to be addressed to develop safe RNAi therapeutics.

Keywords: Biodegradation; Biodistribution; Nanocarrier; Polymer; Stability; siRNA.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Biocompatible Materials
Biological Availability
Drug Carriers*
Humans
Nanoparticles
Pharmacokinetics
Polymers*
RNA, Small Interfering*

Substances

Biocompatible Materials
Drug Carriers
Polymers
RNA, Small Interfering