The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on Poorly Absorbable Drugs.
The polyamidoamine (PAMAM) dendrimer is a highly efficient absorption promoter. In the present study, we studied the absorption-enhancing effects and the mechanism of PAMAM dendrimers with generation 0 to generation 3 (G0⁻G3) and concentrations (0.1⁻1.0%) on the pulmonary absorption of macromolecules. The absorption-enhancing mechanisms were elucidated by microarray, western blotting analysis, and PCR. Fluorescein isothiocyanate-labeled dextrans (FDs) with various molecular weights were used as model drugs of poorly absorbable drugs. The absorption-enhancing effects of PAMAM dendrimers on the pulmonary absorption of FDs were in a generation- and concentration-dependent manner. The G3 PAMAM dendrimer with high effectiveness was considered to the best absorption enhancer for improving the pulmonary absorption of FDs. G3 PAMAM dendrimers at three different concentrations were non-toxic to Calu-3 cells. Based on the consideration between efficacy and cost, the 0.1% G3 PAMAM dendrimer was selected for subsequent studies. The results showed that treatment with a 0.1% G3 PAMAM dendrimer could increase the secretion of organic cation transporters (OCTs), OCT1, OCT2, and OCT3, which might be related to the absorption-enhancing mechanisms of the pulmonary absorption of FDs. These findings suggested that PAMAM dendrimers might be potentially safe absorption enhancers for improving absorption of FDs by increasing the secretion of OCT1, OCT2, and OCT3.
['Lu|Juan|J|', 'Li|Nannan|N|', 'Gao|Yaochun|Y|', 'Li|Nan|N|', 'Guo|Yifei|Y|', 'Liu|Haitao|H|', 'Chen|Xi|X|', 'Zhu|Chunyan|C|', 'Dong|Zhengqi|Z|', 'Yamamoto|Akira|A|']
D000818:Animals D001692:Biological Transport D002460:Cell Line D002470:Cell Survival D050091:Dendrimers D003911:Dextrans D016650:Fluorescein-5-isothiocyanate D006801:Humans D007408:Intestinal Absorption D008168:Lung D012869:Skin Absorption D014018:Tissue Distribution
absorption-enhancement mechanism PAMAM dendrimer fluorescein isothiocyanate-dextrans