Think Beyond The Core: Computationally Decoding the Hydrophilic Corona of Drug-Loaded Polymer Micelles

Area of Science:

• Materials Science
• Biotechnology
• Computational Chemistry

Background:

• Polymeric micelles are crucial for delivering hydrophobic drugs.
• Understanding the molecular interactions within these micelles is essential for optimizing drug delivery.
• Poly(ethylene glycol) (pEG) coronas face challenges due to immunogenicity, necessitating alternative materials like poly(N,N-dimethylacrylamide) (pDMAA) and poly(sarcosine) (pSAR).

Purpose of the Study:

• To investigate the structure and drug interactions in ABA-type triblock copolymer micelles using all-atom molecular dynamics simulations.
• To compare the performance of pEG, pDMAA, and pSAR hydrophilic coronas in drug-loaded micelles.
• To examine the effect of curcumin loading (20% and 60%) on micelle behavior.

Main Methods:

• All-atom molecular dynamics simulations were employed.
• Three micellar formulations with varying hydrophilic coronas (pEG, pDMAA, pSAR) were simulated.
• Curcumin was used as a model hydrophobic drug at moderate and high loading percentages.

Main Results:

• pEG micelles showed higher hydration and looser coronas compared to pDMAA and pSAR micelles.
• Curcumin localized mainly in the core of pEG micelles, but was more distributed in pDMAA and pSAR micelles.
• pDMAA and pSAR micelles demonstrated enhanced stability, tighter curcumin packing, and stronger drug- A-block interactions, particularly pDMAA.

Conclusions:

• pDMAA and pSAR are promising alternatives to pEG for creating stable polymeric micelles with tunable drug interactions.
• Micelle corona composition significantly influences drug distribution, stability, and interactions.
• Molecular dynamics simulations provide valuable insights into the complex behavior of drug-loaded polymeric micelles.