title: Polymer-drug interactions in tyrosine-derived triblock copolymer nanospheres: a computational modeling approach.
abstract: A combination of molecular dynamics (MD) simulations and docking calculations was employed to model and predict polymer-drug interactions in self-assembled nanoparticles consisting of ABA-type triblock copolymers, where A-blocks are poly(ethylene glycol) units and B-blocks are low molecular weight tyrosine-derived polyarylates. This new computational approach was tested on three representative model compounds: nutraceutical curcumin, anticancer drug paclitaxel and prehormone vitamin D3. Based on this methodology, the calculated binding energies of polymer-drug complexes can be correlated with maximum drug loading determined experimentally. Furthermore, the modeling results provide an enhanced understanding of polymer-drug interactions, revealing subtle structural features that can significantly affect the effectiveness of drug loading (as demonstrated for a fourth tested compound, anticancer drug camptothecin). The present study suggests that computational calculations of polymer-drug pairs hold the potential of becoming a powerful prescreening tool in the process of discovery, development and optimization of new drug delivery systems, reducing both the time and the cost of the process.
authors: New Jersey Center for Biomaterials and Department of Chemistry, Rutgers-The State University of New Jersey, 145 Bevier Road, Piscataway, New Jersey 08854, USA.
authors: Aurora D
authors: AD
authors: Costache
authors: Larisa
authors: L
authors: Sheihet
authors: Krishna
authors: K
authors: Zaveri
authors: Doyle D
authors: DD
authors: Knight
authors: Joachim
authors: J
authors: Kohn
mesh_terms: D001665:Binding Sites; D002762:Cholecalciferol / Q000008:administration & dosage / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D004347:Drug Interactions; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D054118:Nanospheres / Q000008:administration & dosage / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D013816:Thermodynamics; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D011108:Polymers; D002762:Cholecalciferol; D014443:Tyrosine; D003474:Curcumin; D017239:Paclitaxel