Plasma Protein Association with High Drug-Loaded Polymer Micelles: An Atomistic Molecular Dynamics Study

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Abstract
Polymeric micelles are widely studied drug delivery platforms whose interactions with plasma proteins influence in vivo performance. However, the combined effects of non-pEG hydrophilic coronas and high drug loading on protein adsorption remain poorly understood. We performed all-atom molecular dynamics (MD) simulations to investigate the association of three plasma proteins: apolipoprotein E (ApoE), human serum albumin (HSA), and immunoglobulin G (IgG), with curcumin-loaded ABA triblock copolymer micelles. To isolate corona effects, micelles shared an hydrophobic core chemistry and differed only in the hydrophilic A-block: poly(ethylene glycol) (pEG), poly(N,N-dimethylacrylamide) (pDMAA), or poly(sarcosine) (pSAR). Two drug loadings (20% and 60% drug/polymer mass ratio) were examined. Binding was assessed via contact areas, hydrogen bonds, and interaction energies. pEG micelles showed the strongest protein association. pDMAA and pSAR exhibited weaker, surface-limited interactions. These simulations provide molecular-level insight into protein adsorption on drug-loaded polymeric micelles and compare alternative hydrophilic A-blocks to pEG.
Funding Information
  • Research Council of Finland (359499)
  • Research Council of Finland Flagship of Advanced Mathematics for Sensing Imaging and Modelling (358944)
  • CSC - IT Center for Science, Finland (2001680)
  • CSC - IT Center for Science, Finland (2006027)
  • CSC - IT Center for Science, Finland (462000354)
  • CSC - IT Center for Science, Finland (462000998)
  • Foundation PS

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