Campus Units

Chemical and Biological Engineering, Materials Science and Engineering, Ames Laboratory

Document Type

Article

Research Focus Area

Health Care Technology and Biomedical Engineering

Publication Version

Accepted Manuscript

Publication Date

11-15-2018

Journal or Book Title

Biochemical Engineering Journal

Volume

139

First Page

8

Last Page

14

DOI

10.1016/j.bej.2018.08.003

Abstract

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.

Comments

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.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Copyright Owner

Elsevier B.V.

Language

en

File Format

application/pdf

Available for download on Friday, November 15, 2019

Published Version

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