Multiscale modelling of drug-polymer nanoparticle assembly identifies parameters influencing drug encapsulation efficiency

Mackenzie, Robert; Booth, Jonathan; Alexander, Cameron; Garnett, Martin; Laughton, Charles A.

Abstract

Using a multiscale (dual resolution) approach combining an atomistic (GROMOS96) and coarse-grain (MARTINI) force field, we have been able to simulate the process of drug-polymer nanoparticle assembly by nanoprecipitation from mixed solvents. Here we present the development and application of this method to the interaction of three poly(glycerol adipate) polymer variants with the anti-cancer drug dexamethasone phosphate. Differences in encapsulation efficiency and drug loading between the polymers are in agreement with the experimental trend. Reference atomistic simulations at key points along the predicted aggregation pathway support the accuracy of the much more compute-efficient multiscale methodology.

Citation

Mackenzie, R., Booth, J., Alexander, C., Garnett, M., & Laughton, C. A. (2015). Multiscale modelling of drug-polymer nanoparticle assembly identifies parameters influencing drug encapsulation efficiency. Journal of Chemical Theory and Computation, 11(6), https://doi.org/10.1021/ct501152a

• Journal Article Type: Article
• Publication Date: May 27, 2015
• Deposit Date: Aug 25, 2015
• Publicly Available Date: Aug 25, 2015
• Journal: Journal of Chemical Theory and Computation
• Print ISSN: 1549-9618
• Electronic ISSN: 1549-9626
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 6
• DOI: https://doi.org/10.1021/ct501152a
• Keywords: Nanoprecipitation, Poly(glycerol adipate), Multiscale Modelling, Drug Delivery
• Public URL: https://nottingham-repository.worktribe.com/output/751239
• Publisher URL: http://pubs.acs.org/doi/full/10.1021/ct501152a
• Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Theory and Computation, copyright © American Chemical Society after peer review and technical editing by the publisher.; To access the final edited and published work see [insert ACS Articles on Request author-directed link to; Published Work, see http://pubs.acs.org/page/policy/articlesonrequest/index.html].