Transport properties and aggregation phenomena of polyoxyethylene sorbitane monooleate (polysorbate 80) in pig gastrointestinal mucin and mucus.
The aqueous environment in the gastrointestinal tract frequently requires solubilization of hydrophobic drug molecules in appropriate drug delivery vehicles. An effective uptake/absorption and systemic exposure of a drug molecule entails many processes, one being transport properties of the vehicles through the mucus layer. The mucus layer is a complex mixture of biological molecules. Among them, mucin is responsible of the gel properties of this layer. In this study, we have investigated the diffusion of polyoxyethylene sorbitane monooleate (polysorbate 80), a commonly used nonionic surfactant, in aqueous solution, in mucin solutions at 0.25 and 5 wt %, and in mucus. These measurements were done by using the pulsed field gradient spin echo nuclear magnetic resonance (PGSE-NMR) technique. We conclude that polysorbate 80 is a mixture of non-surface-active molecules that can diffuse freely through all the systems investigated and of surface-active molecules that form micellar structures with transport properties strongly dependent on the environment. Polysorbate 80 micelles do not interact with mucin even though their diffusion is hindered by obstruction of the large mucin molecules. On the other hand, the transport is slowed down in mucus due to interactions with other components such as lipids depots. In the last part of this study, a hydrophobic NMR probe molecule has been included in the systems to mimic a hydrophobic drug molecule. The measurements done in aqueous solution revealed that the probe molecules were transported in a closely similar way as the polysorbate 80 micelles, indicating that they were dissolved in the micellar core. The situation was more complex in mucus. The probe molecules seem to dissolve in the lipid depots at low concentrations of polysorbate 80, which slows down their transport. At increasing concentration of polysorbate 80, the diffusion of the probe molecules increases indicating a continuous dissolution of hexamethyldisilane in the core of polysorbate 80 micelles.
Lafitte
G
G
Physical Chemistry 1, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden. geraldine.lafitte@fkem1.lu.se
Thuresson
K
K
Jarwoll
P
P
Nydén
M
M
D000818:Animals; D001693:Biological Transport, Active; D004058:Diffusion; D016503:Drug Delivery Systems; D041981:Gastrointestinal Tract / Q000378:metabolism; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D009077:Mucins / Q000737:chemistry / Q000378:metabolism*; D009093:Mucus / Q000737:chemistry / Q000378:metabolism*; D011136:Polysorbates / Q000737:chemistry / Q000493:pharmacokinetics*; D012996:Solutions; D013501:Surface-Active Agents / Q000737:chemistry / Q000493:pharmacokinetics; D013552:Swine; D014867:Water
D008823:Micelles; D009077:Mucins; D011136:Polysorbates; D012996:Solutions; D013501:Surface-Active Agents; D014867:Water