title: Multiscale modeling of drug-polymer nanoparticle assembly identifies parameters influencing drug encapsulation efficiency.
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.
authors.forename: R
authors.initials: R
authors.lastname: Mackenzie
authors.affiliation: Pharmaceutical Development, AstraZeneca , Macclesfield SK10 2NA, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Booth
authors.forename: C
authors.initials: C
authors.lastname: Alexander
authors.forename: M C
authors.initials: MC
authors.lastname: Garnett
authors.forename: C A
authors.initials: CA
authors.lastname: Laughton
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000737:chemistry*; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D011091:Polyesters; D012997:Solvents; C517626:poly(glycerol-adipate); D003907:Dexamethasone