open access publication

Article, 2024

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

Advanced Materials Interfaces, ISSN 2196-7350, Volume 11, 19, 10.1002/admi.202400107

Contributors

Tollemeto, Matteo 0000-0002-6220-2877 (Corresponding author) [1] Badillo-Ramírez, Isidro 0000-0002-9153-7158 [1] Thamdrup, Lasse Højlund Eklund 0000-0002-9498-1529 [1] Li, Yudong 0009-0006-9140-5733 [2] Ghavami, Mahdi 0000-0003-2965-588X [1] Padial, Tania Patiño [2] Christensen, Jørn Bolstad 0000-0002-7641-8302 [3] Van Hest, Jan C M 0000-0001-7973-2404 [2] Boisen, Anja [1]

Affiliations

  1. [1] Danish National Research Foundation
  2. [NORA names: Danish National Research Foundation; Non-Profit Organisations; Denmark; Europe, EU; Nordic; OECD];
  3. [2] Eindhoven University of Technology
  4. [NORA names: Netherlands; Europe, EU; OECD];
  5. [3] University of Copenhagen
  6. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD]

Abstract

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.

Keywords

Brownian motion, Raman scattering, amount, applications, approach, assay, backbone, barriers, binding, binding amount, binding of mucin, binding sites, biological barriers, body, bonds, calorimetry method, chemistry, clinical application, colloidal chemistry, colloidal systems, comprehensive study, core, crystal microbalance, delivery formulations, delivery nanocarriers, delivery technologies, development, differences, dissipation, distribution, drug, drug delivery formulations, drug delivery nanocarriers, drug delivery technology, fabrication, field, field of surface, formulation, hydrogen bonds, hydrophilic core, improvement, in vitro studies, interaction, isothermal titration calorimetry methods, layer, method, micelles, microbalance, molecular interactions, motility, motility studies, motion, mucin, mucin layer, mucosal layer, multidisciplinary approach, nanocarriers, nanoparticles, novel techniques, optimal performance, particle distribution, particles, physicochemical interactions, polymeric micelles, polymeric nanoparticles, polymerization, potential, predominant hydrogen bonding, properties, protein, protein backbone, quartz, quartz crystal microbalance, results, scattering, sites, staining assay, study, surface, surface binding, surface-enhanced Raman scattering, system, systematic study, technique, technology, viscoelastic properties

Funders

  • Danish National Research Foundation
  • Novo Nordisk Foundation
  • The Velux Foundations

Data Provider: Digital Science