TY - JOUR

T1 - A Systematic Study on the Physicochemical Interactions Between Polymeric Micelles and Mucin

T2 - Toward the Development of Optimal Drug Delivery Nanocarriers

AU - Tollemeto, Matteo

AU - Badillo-Ramírez, Isidro

AU - Thamdrup, Lasse Højlund Eklund

AU - Li, Yudong

AU - Ghavami, Mahdi

AU - Padial, Tania Patiño

AU - Christensen, Jørn B.

AU - van Hest, Jan

AU - Boisen, Anja

N1 - Funding Information: The authors would like to thank associate Prof. Leticia Hosta\u2010Rigau for the use of DLS, and Prof. Peter Westh, for facilitating the access to the ITC instrument. The authors would like to acknowledge the Danish National Research Foundation (DNRF122) and Villum Fonden (Grant No. 9301) for intelligent drug delivery and sensing using microcontainers and nanomechanics (IDUN) and the Novo Nordisk Foundation (NNF17OC0026910). Publisher Copyright: © 2024 The Authors. Advanced Materials Interfaces published by Wiley-VCH GmbH.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - mucoadhesion

KW - mucosal barriers

KW - nanomedicine

KW - oral delivery

KW - polymeric micelles

U2 - 10.1002/admi.202400107

DO - 10.1002/admi.202400107

M3 - Journal article

AN - SCOPUS:85192164720

VL - 11

JO - Advanced Materials Interfaces

JF - Advanced Materials Interfaces

SN - 2196-7350

IS - 19

M1 - 2400107

ER -