Lanthanum carbonate, a potent and selective phosphate binder, is transported and absorbed mainly via M cells in gastrointestinal tract

Abstract

Abstract This study aimed to investigate the transportation and absorption mechanism of lanthanum carbonate [La2(CO3)3] through the gastrointestinal (GI) tract using in vitro and in vivo models. The results demonstrated that La2(CO3)3 can be dissolved in gastric fluids and precipitated into lanthanum phosphate as the main transformed specie in intestinal fluid. Using Caco-2 cell monoculture and Caco-2/Raji B cell coculture models to simulate the intestinal epithelium and microfold (M) cells, it was found that the amount of lanthanum transported in Caco-2/Raji B coculture model was significantly higher than that in Caco-2 monoculture model (about 50 times higher), indicating that M cells play an important role in the intestinal absorption of La2(CO3)3. Furthermore, oral administration of La2(CO3)3 to Balb/c mice demonstrated that lanthanum can be absorbed by both Peyer's patches (PPs) and non-PPs intestinal epithelium, with a higher amount of absorption in the PPs per unit weight. This finding further confirmed that the lanthanum absorption in GI tract could be mainly due to the contribution of M cells. Meanwhile, the administration of La2(CO3)3 caused a marked lanthanum accumulation in liver, accompanied by the activation of Kupffer cells. This study clarified how La2(CO3)3 is absorbed through the GI tract to enter the body and would be helpful to evaluate its potential biological consequences of accumulation in human beings.