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Paper   IPM / Nano-Sciences / 14372
School of Nano Science
  Title:   Effects of cholesterol concentration on the interaction of cytarabine with lipid membranes: a molecular dynamics simulation study
1.  Leila Karami
2.  Seifollah Jalili
  Status:   Published
  Journal: J. Biomolecular Structure and Dynamics
  No.:  6
  Vol.:  33
  Year:  2015
  Pages:   1254-1268
  Publisher(s):   Taylor & Francis
  Supported by:  IPM
Liposomal cytarabine, DepoCyt, is a chemotherapy agent which is used in cancer treatment. This form of cytarabine has more efficacy and fewer side effects relative to the other forms. Since DepoCyt contains the cytarabine encapsulated within phosphatidylcholine and the sterol molecules, we modeled dioleoylphosphatidylcholine (DOPC)/cholesterol bilayer membrane as a carrier for cytarabine to study drug�??bilayer interactions. For this purpose, we performed a series of united-atom molecular dynamics (MD) simulations for 25 ns to investigate the interactions between cytarabine and cholesterol-containing DOPC lipid bilayers. Only the uncharged form of cytarabine molecule was investigated. In this study, different levels of the cholesterol content (0, 20, and 40cytarabine molecule inside the bilayer membrane. Properties such as membrane thickness, area per lipid, diffusion coefficient, mass density, bilayer packing, order parameters, and intermolecular interactions were examined. The results show that by increasing the cholesterol concentration in the lipid bilayers, the bilayer thickness increases and area per lipid decreases. Moreover, in accordance with the experiments, our calculations show that cholesterol molecules have ordering effect on the hydrocarbon acyl chains. Furthermore, the cytarabine molecule preferentially occupies the polar region of the lipid head groups to form specific interactions (hydrogen bonds). Our results fully support the experimental data. Our finding about drug�??bilayer interaction is crucial for the liposomal drug design.

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