Polymer-drug interactions in tyrosine-derived triblock copolymer nanospheres: A computational modeling approach

Aurora D. Costache, Larisa Sheihet, Krishna Zaveri, Doyle D. Knight, Joachim Kohn

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1620-1627
Number of pages8
JournalMolecular Pharmaceutics
Issue number5
StatePublished - Oct 5 2009

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Molecular Medicine
  • Pharmaceutical Science


  • Ab initio
  • Computational modeling
  • Docking
  • Drug delivery
  • Drug-polymer interactions
  • Molecular dynamics
  • Nanoparticles
  • Paclitaxel
  • Vitamin D3


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