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Molecules 2018, 23(8), 2001; https://doi.org/10.3390/molecules23082001

The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on Poorly Absorbable Drugs

1,†
,
1,2,†
,
1
,
1
,
1,3
,
1,3
,
1
,
1,3
,
1,3,* and 4,*
1
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China
2
Research Center on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, China
3
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China
4
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 18 July 2018 / Revised: 2 August 2018 / Accepted: 6 August 2018 / Published: 10 August 2018
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Abstract

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. View Full-Text
Keywords: PAMAM dendrimer; fluorescein isothiocyanate-dextrans; absorption-enhancement; mechanism PAMAM dendrimer; fluorescein isothiocyanate-dextrans; absorption-enhancement; mechanism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Lu, J.; Li, N.; Gao, Y.; Li, N.; Guo, Y.; Liu, H.; Chen, X.; Zhu, C.; Dong, Z.; Yamamoto, A. The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on Poorly Absorbable Drugs. Molecules 2018, 23, 2001.

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