Abstract

Synthetic polymers of a specific shape and size play major role in drug delivery systems. Dendrimers are unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape with potential applications in gene and drug delivery. We examine the interaction of several dendrimers of different compositions mPEG-PAMAM (G3), mPEG-PAMAM (G4) and PAMAM (G4) with hydrophilic and hydrophobic drugs cisplatin, resveratrol, genistein and curcumin at physiological conditions. FTIR and UV-visible spectroscopic methods as well as molecular modeling were used to analyse drug binding mode, the binding constant and the effects of drug complexation on dendrimer stability and conformation. Structural analysis showed that cisplatin binds dendrimers in hydrophilic mode via Pt cation and polymer terminal NH2 groups, while curcumin, genistein and resveratrol are located mainly in the cavities binding through both hydrophobic and hydrophilic contacts. The overall binding constants of durg-dendrimers are ranging from 102 M-1 to 103 M-1. The affinity of dendrimer binding was PAMAM-G4>mPEG-PAMAM-G4>mPEG-PAMAM-G3, while the order of drug-polymer stability was curcumin>cisplatin>genistein>resveratrol. Molecular modeling showed larger stability for genisten-PAMAM-G4 (ΔG = -4.75 kcal/mol) than curcumin-PAMAM-G4 ((ΔG = -4.53 kcal/mol) and resveratrol-PAMAM-G4 ((ΔG = -4.39 kcal/mol). Dendrimers might act as carriers to transport hydrophobic and hydrophilic drugs.

Department(s)

Chemistry

Document Type

Article

DOI

https://doi.org/10.1371/journal.pone.0033102

Rights Information

© 2012 Abderrexak et al. This is an open access article distributedunder the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproductionin any medium, provided the original author and source are credited.

Keywords

polymers, vibration, drug delivery, drug synthesis, absorption spectroscopy, infrared spectroscopy, molecular structure, cations

Publication Date

2012

Recommended Citation

Abderrezak, Amine, Philippe Bourassa, Jean-Sebastian Mandeville, Reza Sedaghat-Herati, and Heidar-Ali Tajmir-Riahi. "Dendrimers bind antioxidant polyphenols and cisplatin drug." PloS one 7, no. 3 (2012).

Journal Title

PLOS ONE

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