| Polyamidoamine dendrimers can improve the pulmonary absorption of insulin and calcitonin in rats. | |
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MedLine Citation:
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PMID: 21374620 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The absorption-enhancing effects of polyamidoamine (PAMAM) dendrimers with various generations (G0-G3) and concentrations [0.1%-1.0% (w/v)] on the pulmonary absorption of peptide and protein drugs were studied in rats. Insulin and calcitonin were chosen as models of peptide and protein drugs, and their pulmonary absorption with or without PAMAM dendrimers was examined by in vivo pulmonary absorption studies. PAMAM dendrimers significantly increased the pulmonary absorption of insulin and calcitonin in rats, and their absorption-enhancing effects were generation dependent. The rank order of absorption enhancement effect of these PAMAM dendrimers was G3 > G2 > G1 > G0. For the same generation, the absorption-enhancing effects of PAMAM dendrimers were shown to be concentration dependent. The toxicity of these PAMAM dendrimers in the lung tissues was evaluated by measuring the release of protein and the activities of lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF). The PAMAM dendrimers with various generations and concentrations did not significantly increase the release of protein and the activities of LDH in BALF, indicating that these dendrimers did not cause any membrane damage to the lung tissues. The zeta potentials of insulin and calcitonin solutions changed to positive by the addition of PAMAM dendrimers, and the degree of positive charge as determined by the zeta potentials was linearly correlated with the absorption-enhancing effects of the PAMAM dendrimers. This positive charge of the PAMAM dendrimers might be related to their absorption-enhancing mechanisms for improving the pulmonary absorption of insulin and calcitonin in rats. In conclusion, the PAMAM dendrimers are suitable absorption enhancers to improve the pulmonary absorption of insulin and calcitonin without any membrane damage to the respiratory tissues. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1866-1878, 2011. |
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Authors:
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Zhengqi Dong; Khuriah Abdul Hamid; Yang Gao; Yulian Lin; Hidemasa Katsumi; Toshiyasu Sakane; Akira Yamamoto |
Publication Detail:
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Type: Journal Article Date: 2010-12-28 |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 100 ISSN: 1520-6017 ISO Abbreviation: J Pharm Sci Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-03-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: United States |
Other Details:
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Languages: eng Pagination: 1866-78 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Wiley-Liss, Inc. |
Affiliation:
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Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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