Diffusions of β-cyclodextrins in mucus studied by 19F diffusion NMR

Abstract

β-Cyclodextrin (β-CD) based materials have been widely used as drug carriers for pharmaceutical applications. To understand the diffusion of β-CDs in mucus is important for selecting β-CD based drug carriers for applications targeting mucosal absorption because the surfaces of many biological membranes are covered with a highly viscous aqueous mucus layer which forms relatively effective diffusion barriers for drugs. In this study, 19F self-diffusion NMR technique has been applied to study the self-diffusions of β-CDs in mucus. The 19F NMR signals arose from 1-fluoroadamantane molecules entrapped in the cavities of β-CDs. The diffusive abilities of different β-CDs in mucus were assessed through analyzing the diffusion coefficients using the presented kinetic model, and Ogston’s and Renkin’s diffusion models for hydrogel systems. The kinetic results show that 2-hydroxypropyl-β-CD and 2-Carboxyethyl-β-CD have the smallest binding affinities to bovine submaxillary mucin and human nasal mucin among five tested β-CDs. The mesh sizes of the bovine submaxillary mucus at different concentrations and that of the human nasal mucus were evaluated using the diffusion models. We hope that this 19F diffusion method will be useful to study the diffusion of β-CD based materials in other biological systems.