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

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

Authors

Robert Mackenzie paxrm@exmail.nottingham.ac.uk

Jonathan Booth jonathan.booth@astrazeneca.com

Martin Garnett m.garnett@nottingham.ac.uk

CHARLES LAUGHTON CHARLES.LAUGHTON@NOTTINGHAM.AC.UK
Professor of Computational Pharmaceutical Science



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.

Journal Article Type Article
Publication Date May 27, 2015
Journal Journal of Chemical Theory and Computation
Print ISSN 1549-9618
Electronic ISSN 1549-9618
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 11
Issue 6
APA6 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), doi:10.1021/ct501152a
DOI https://doi.org/10.1021/ct501152a
Keywords Nanoprecipitation, Poly(glycerol adipate), Multiscale Modelling, Drug Delivery
Publisher URL http://pubs.acs.org/doi/full/10.1021/ct501152a
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
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/pag...sonrequest/index.html].

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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