Nanoparticles for cytosolic delivery of important biomolecular drugs such as DNA, RNA, peptides, and proteins

0437617 - ÚMCH 2015 RIV NL eng J - Journal Article
Sedlák, M. - Koňák, Čestmír - Dybal, Jiří
Nanoparticles for cytosolic delivery of important biomolecular drugs such as DNA, RNA, peptides, and proteins.
The Open Conference Proceedings Journal. Roč. 1, č. 2010 (2010), s. 87-90. ISSN 2210-2892
Institutional research plan: CEZ:AV0Z40500505
Keywords : cytosolic delivery * nanoparticle carriers * poly(ethylacrylic acid)
Subject RIV: CD - Macromolecular Chemistry
http://benthamopen.com/ABSTRACT/TOPROCJ-1-87

Taking advantage of the pH difference between an endosome and the cytosol (that of the endosome being lower by 1-2 units), it was proved that totally synthetic (exhibiting minimal antigenicity) pH-sensitive, membranedisrupting polymers such as poly(ethylacrylic acid) and poly(propylacrylic acid) significantly enhance in vivo transfections [1-3]. Their effect is based on the ability to disrupt membranes at the pH of the endosome but be non-lytic at pH 7.4. We have developed recently a new route to the preparation of poly(ethylacrylic acid) and poly(propylacrylic acid) nanoparticles based on the self-assembly mechanism of polymeric chains, i.e. via action of physical bonds [4,5]. Ideas behind this new route are reviewed together with the technical realization. Possible applications in drug delivery are discussed. We anticipate that these nanoparticles will also enable to utilize the EPR (Enhanced Permeability and Retention) effect in tumor tissues, meaning that certain sizes of large particles tend to accumulate in tumor tissue much more than they do in normal tissues. Nanoparticles have well controllable size, posses a mild acceptable degree of polydispersity, are stable over long periods of time (excellent shelf-life) and are stable in a broad range of salt concentrations including physiological. Nanoparticles have low density (loose and open internal structure) which is advantageous for loading with drugs. The developed self-assembly mechanism [4] is promising also with respect to the preparation of nanoparticles from other similar polymers.
Permanent Link: http://hdl.handle.net/11104/0241135