Effects of arginine-based surface modifications of liposomes for drug delivery in Caco-2 colon carcinoma cells

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2018-11-15
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Neuberger, Kendall
Boddupalli, Anuraag
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Bratlie, Kaitlin
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Ames National Laboratory

Ames National Laboratory is a government-owned, contractor-operated national laboratory of the U.S. Department of Energy (DOE), operated by and located on the campus of Iowa State University in Ames, Iowa.

For more than 70 years, the Ames National Laboratory has successfully partnered with Iowa State University, and is unique among the 17 DOE laboratories in that it is physically located on the campus of a major research university. Many of the scientists and administrators at the Laboratory also hold faculty positions at the University and the Laboratory has access to both undergraduate and graduate student talent.

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Materials Science and Engineering

The Department of Materials Science and Engineering teaches the composition, microstructure, and processing of materials as well as their properties, uses, and performance. These fields of research utilize technologies in metals, ceramics, polymers, composites, and electronic materials.

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The Department of Materials Science and Engineering was formed in 1975 from the merger of the Department of Ceramics Engineering and the Department of Metallurgical Engineering.

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1975-present

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Chemical and Biological Engineering

The function of the Department of Chemical and Biological Engineering has been to prepare students for the study and application of chemistry in industry. This focus has included preparation for employment in various industries as well as the development, design, and operation of equipment and processes within industry.Through the CBE Department, Iowa State University is nationally recognized for its initiatives in bioinformatics, biomaterials, bioproducts, metabolic/tissue engineering, multiphase computational fluid dynamics, advanced polymeric materials and nanostructured materials.

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The Department of Chemical Engineering was founded in 1913 under the Department of Physics and Illuminating Engineering. From 1915 to 1931 it was jointly administered by the Divisions of Industrial Science and Engineering, and from 1931 onward it has been under the Division/College of Engineering. In 1928 it merged with Mining Engineering, and from 1973–1979 it merged with Nuclear Engineering. It became Chemical and Biological Engineering in 2005.

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1913 - present

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  • Department of Chemical Engineering (1913–1928)
  • Department of Chemical and Mining Engineering (1928–1957)
  • Department of Chemical Engineering (1957–1973, 1979–2005)
    • Department of Chemical and Biological Engineering (2005–present)

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Liposomal encapsulation of chemotherapeutics improves circulation time and decreases off-target effects through the enhanced permeability and retention (EPR) effect. Improving the efficacy of these drug carriers through surface modification could benefit patients. A library of arginine derivatives was conjugated to liposomes through carbodiimide chemistry. Both unmodified and modified liposomes were loaded with doxorubicin and exposed to Caco-2 colon carcinoma cells to measure the half maximal inhibitory concentration (IC50). Most of the modifications improved the toxicity of doxorubicin. Principal component analysis (PCA) was used to uncover correlations between physicochemical properties (lipophilicity (log P), partition coefficient (log D), number of hydrogen bond donors, number of hydrogen bond acceptors, freely rotating bonds, surface tension, polarization surface area, and isoelectric point) and the IC50 of encapsulated doxorubicin. Generalized rules for improved toxicity were also developed, which stated that improved drug carriers should have at least 4 hydrogen bond donors, between 4 and 6 freely rotating bonds, an isoelectric point above 5.5, and a log P between -2 and -1. Using these relationships along with previously obtained correlations for macrophages, selective targeting and the understanding of how to rationally design such drug carriers can be improved.

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This is a manuscript of an article published as Neuberger, Kendall, Anuraag Boddupalli, and Kaitlin M. Bratlie. "Effects of arginine-based surface modifications of liposomes for drug delivery in Caco-2 colon carcinoma cells." Biochemical Engineering Journal 139 (2018): 8-14. doi: 10.1016/j.bej.2018.08.003. Posted with permission.

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Mon Jan 01 00:00:00 UTC 2018
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