Publication
Journal of Physical Chemistry B
Paper

Dynamical Interactions of 5-Fluorouracil Drug with Dendritic Peptide Vectors: The Impact of Dendrimer Generation, Charge, Counterions, and Structured Water

View publication

Abstract

Molecular dynamics simulations are utilized to investigate the interactions between the skin cancer drug 5-fluorouracil (5FU) and peptide-based dendritic carrier systems. We find that these drug-carrier interactions do not conform to the traditional picture of long-time retention of the drug within a hydrophobic core of the dendrimer carrier. Rather, 5FU, which is moderately soluble in its own right, experiences weak, transient chattering interactions all over the dendrimer, mediated through multiple short-lived hydrogen bonding and close contact events. We find that charge on the periphery of the dendrimer actually has a negative effect on the frequency of drug-carrier interactions due to a counterion screening effect that has not previously been observed. However, charge is nevertheless an important feature since neutral dendrimers are shown to have a significant mutual attraction that can lead to clustering or agglomeration. This clustering is prevented due to charge repulsion for the titrated dendrimers, such that they remain independent in solution.

Date

20 Jun 2016

Publication

Journal of Physical Chemistry B

Authors

Share