A Systematic Study on the Physicochemical Interactions Between Polymeric Micelles and Mucin: Toward the Development of Optimal Drug Delivery Nanocarriers

Matteo Tollemeto*, Isidro Badillo-Ramírez, Lasse Højlund Eklund Thamdrup, Yudong Li, Mahdi Ghavami, Tania Patiño Padial, Jørn B. Christensen, Jan van Hest, Anja Boisen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

The optimal performance of drug delivery formulations, including polymeric nanoparticles, relies on particle distribution throughout the body and the interactions with biological barriers, particularly mucosal layers, which often limit their potential. A systematic and comprehensive study is presented through a multidisciplinary approach combining conventional and novel techniques for in vitro studies to understand the key molecular interactions between polymeric micelles and mucin. The results shows that polymeric micelles are integrates within the mucin layer, mirroring its viscoelastic properties, evidenced as a dissipation difference of 0.1 ± 0.44, measured by quartz crystal microbalance with dissipation. Surface-enhanced Raman scattering reveals predominant hydrogen bonding within the mucin's hydrophilic core, while the isothermal titration calorimetry method confirms multiple non-specific binding sites on the protein backbone. By performing the periodic acid-Schiff stain assay, a binding amount of 0.20 mg of mucin per milligram of nanoparticles is quantified. Furthermore, motility studies show the surface binding of mucin on the polymeric nanoparticles influencing their Brownian motion. This study sheds light toward the improvement for a better drug delivery formulation and fabrication of optimal nanoparticle colloidal systems, which can advance translational drug delivery technologies into clinical application while enriching the field of surface and colloidal chemistry.

Original languageEnglish
Article number2400107
JournalAdvanced Materials Interfaces
Volume11
Issue number19
Number of pages12
ISSN2196-7350
DOIs
Publication statusPublished - 2024

Keywords

  • Mucoadhesion
  • Mucosal barriers
  • Nanomedicine
  • Oral delivery
  • Polymeric micelles

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