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

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• 作者：Sergio De Luca ; Prasenjit Seal ; Defang Ouyang ; Harendra S. Parekh ; Sridhar Kumar Kannam ; Sean C. Smith
• 刊名：Journal of Physical Chemistry B
• 出版年：2016
• 出版时间：June 30, 2016
• 年：2016
• 卷：120
• 期：25
• 页码：5732-5743
• 全文大小：718K
• 年卷期：0
• ISSN：1520-5207

文摘

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.