Impact of digestion on the transport of dextran-loaded self-emulsified nanoemulsion through MDCK epithelial cell monolayer and rat intestines.

Many of the lipids and surfactants used to prepare the self-emulsified nanoemulsion (SEN) are subjected to the gastro-intestinal enzymatic digestion, which may affect the absorption of the loaded drug. The present study was to investigate the impact of such digestion on the transport of hydrophilic macromolecules (10-kDa dextran as the model compound) loaded in SEN through the MDCK cell monolayer and ex-vivo rat intestines. FITC-labeled dextran (FD) was loaded inside the inner oil phase of SEN by the formation of FD-phospholipid solid dispersion (FDPS). After digestion, the droplet size increased from 31.06 ± 2.10 nm to 494.6 ± 22.1 nm, and the FD content in the external aqueous phase increased from 41.6 ± 4.2% to 61.1 ± 4.4%. Compared to the FD solution, SEN without digestion enhanced the transport of FD through MDCK cell monolayer 4.1 times and through rat intestines 3.0-7.4 times. However, the digestion reduced the transport of FD 3.5 times through MDCK cell monolayer and 1.3-2.0 times through rat intestines, compared to that without digestion. This reduction was due to the destruction of lipid nano-droplets and release of FD to the external aqueous phase of SEN. This finding should be considered when SEN is used as a delivery system for hydrophilic macromolecules.