Intestinal transport mechanism of HA-LOR microspheres with different molecular weights in the MDCK cell model

In this study, LOR microspheres with different molecular weights of hyaluronic acid (HA) were prepared by spray drying method using the second-generation antihistamine loratadine (LOR) as a model drug. A small intestinal transmembrane transport model was used to study the effect of HA molecular weight on small intestinal transmembrane transport and to explore the mechanism of HA molecular weight on intestinal absorption. The transmembrane transport of HA-LOR microspheres of different molecular weights was investigated by adding several inhibitors related to drug transmembrane transport and cellular function in the MDCK cell model. The results showed that low, medium and high molecular weight HA in HA-LOR microspheres had no effect on P-gp efflux and macrocytidine and had no effect on the transmembrane of LOR microspheres; medium molecular weight HA could affect Ca₂₊ channel and has an effect on the transmembrane transport of LOR microspheres; high molecular weight HA can affect clathrin-mediated endocytosis, lipid microcapsule-mediated endocytosis and endosomes, indicating that high molecular weight HA-LOR microspheres are effective in the intestinal tract. The uptake of LOR can be facilitated by the action of uptake enhancers, the action of Ca₂₊ channels and the uptake of ATP to LOR.