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The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on Poorly Absorbable Drugs.
Molecules. 2018 Aug 10; 23(8)M

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.

Authors+Show Affiliations

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. jlu@implad.ac.cn.Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. linan837@163.com. Research Center on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, China. linan837@163.com.Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. 17801085365@163.com.Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. 17801080758@163.com.Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. yfguo@implad.ac.cn. 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. yfguo@implad.ac.cn.Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. htliu@implad.ac.cn. 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. htliu@implad.ac.cn.Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. chenx_implad@163.com.Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. cyzhu@implad.ac.cn. 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. cyzhu@implad.ac.cn.Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. zqdong@implad.ac.cn. 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. zqdong@implad.ac.cn.Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. yamamoto@mb.kyoto-phu.ac.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30103462

Citation

Lu, Juan, et al. "The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer On Poorly Absorbable Drugs." Molecules (Basel, Switzerland), vol. 23, no. 8, 2018.
Lu J, Li N, Gao Y, et al. The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on Poorly Absorbable Drugs. Molecules. 2018;23(8).
Lu, J., Li, N., Gao, Y., Li, N., Guo, Y., Liu, H., Chen, X., Zhu, C., Dong, Z., & Yamamoto, A. (2018). The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on Poorly Absorbable Drugs. Molecules (Basel, Switzerland), 23(8). https://doi.org/10.3390/molecules23082001
Lu J, et al. The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer On Poorly Absorbable Drugs. Molecules. 2018 Aug 10;23(8) PubMed PMID: 30103462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on Poorly Absorbable Drugs. AU - Lu,Juan, AU - Li,Nannan, AU - Gao,Yaochun, AU - Li,Nan, AU - Guo,Yifei, AU - Liu,Haitao, AU - Chen,Xi, AU - Zhu,Chunyan, AU - Dong,Zhengqi, AU - Yamamoto,Akira, Y1 - 2018/08/10/ PY - 2018/07/18/received PY - 2018/08/02/revised PY - 2018/08/06/accepted PY - 2018/8/15/entrez PY - 2018/8/15/pubmed PY - 2018/11/9/medline KW - PAMAM dendrimer KW - absorption-enhancement KW - fluorescein isothiocyanate-dextrans KW - mechanism JF - Molecules (Basel, Switzerland) JO - Molecules VL - 23 IS - 8 N2 - 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. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/30103462/The_Effect_of_Absorption_Enhancement_and_the_Mechanism_of_the_PAMAM_Dendrimer_on_Poorly_Absorbable_Drugs_ L2 - https://www.mdpi.com/resolver?pii=molecules23082001 DB - PRIME DP - Unbound Medicine ER -