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

J Chem Theory Comput. 2015 Jun 9;11(6):2705-13. doi: 10.1021/ct501152a. Epub 2015 May 27.

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 anticancer 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 computationally efficient multiscale methodology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Dexamethasone / analogs & derivatives
  • Dexamethasone / chemistry*
  • Models, Molecular
  • Nanoparticles / chemistry*
  • Polyesters / chemistry*
  • Solvents / chemistry

Substances

  • Antineoplastic Agents
  • Polyesters
  • Solvents
  • poly(glycerol-adipate)
  • Dexamethasone