Session Speaker

Nanoparticles for Cytosolic Delivery of Important Biomolecular Drugs Such as DNA, RNA, Peptides, and Proteins
Marian Sedlak, Cestmir Konak, Jiri Dybal
Slovak Republic

One of the challenges in the drug delivery area is the intracellular delivery via endocytosis followed by endosomal escape due to the disruption of the endosomal membrane and release of important biomolecular drugs such as DNA, RNA, peptides, and proteins to the cytoplasm before they are trafficked to lysosomes and degraded by lysosomal enzymes. 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 polymers such as poly(ethylacrylic acid) and especially poly(propylacrylic acid) significantly enhance in vivo transfections (1,2). 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 (3,4). 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 (3) is promising also with respect to the preparation of nanoparticles from other similar polymers.

References

1. A. S. Hoffman et al., Journal of Controlled Release 78 (2002), 295-303, 295-303.

2. A. S. Hoffman et al., Polym. Adv. Technol. 13 (2002), 992-999

3. M. Sedlák, C. Koňák, Macromolecules (2009), in press.

4. M. Sedlák, Č. Ko 8;ák, J. Dybal, Macromolecules (2009), in press.

This work was realized within the frame of the project "Centre of Excellence for Advanced Materials with Nano- and Submicron Structure", which is supported by the Operational Program "Research and Development" financed through the European Regional Development Fund.