Effect of the Structure of Therapeutic Adenosine Analogues on Stability and Surface Electrostatic Potential of their Complexes with Poly(propyleneimine) Dendrimers

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Michal Gorzkiewicz - , Lodz University of Technology (Author)
  • Dietmar Appelhans - , Leibniz Institute of Polymer Research Dresden (Author)
  • Susanne Boye - , Leibniz Institute of Polymer Research Dresden (Author)
  • Albena Lederer - , Leibniz Institute of Polymer Research Dresden, TUD Dresden University of Technology, University of Stellenbosch (Author)
  • Brigitte Voit - , Chair of Organic Chemistry of Polymers, Leibniz Institute of Polymer Research Dresden, TUD Dresden University of Technology (Author)
  • Barbara Klajnert-Maculewicz - , Lodz University of Technology (Author)

Abstract

Poly(propyleneimine) glycodendrimers are proposed as nanocarriers for triphosphate forms of anticancer adenosine analogues to improve the efficiency of chemotherapy and to overcome drug resistance mechanisms. This approach has proven successful for fludarabine administration-an autonomous way of cellular entry of a nucleotide-dendrimer noncovalent complex enables an increase in the intracellular accumulation and cytotoxic activity of the active metabolite of the drug. However, the attempt to apply an analogous strategy for clofarabine results in the inhibition of drug activity. To better understand this phenomenon, characterization and comparison of drug-dendrimer complexes were needed to indicate the differences in their surface properties and the strengths of fludarabine-dendrimer and clofarabine-dendrimer interactions. Here, zeta potential measurements, ultrafiltration, and asymmetric flow field-flow fractionation are applied to determine the surface electrostatic potential and stability of nucleotide-dendrimer formulations. This approach significantly extends the authors' research on the complexation potential of perfectly branched macromolecules, ultimately explaining previously observed differences and their consequences.

Details

Original languageGerman
Number of pages5
JournalMacromolecular rapid communications
Volume40
Issue number15
Publication statusPublished - Aug 2019
Peer-reviewedYes

External IDs

PubMed 31136015
Scopus 85068721050
ORCID /0000-0002-4531-691X/work/148608054

Keywords

Keywords

  • PPI glycodendrimers, Clofarabine, Complexation, Drug delivery systems, Fludarabine