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Polyamidoamine dendrimers can improve the pulmonary absorption of insulin and calcitonin in rats.
J Pharm Sci. 2011 May; 100(5):1866-78.JP

Abstract

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.

Authors+Show Affiliations

Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21374620

Citation

Dong, Zhengqi, et al. "Polyamidoamine Dendrimers Can Improve the Pulmonary Absorption of Insulin and Calcitonin in Rats." Journal of Pharmaceutical Sciences, vol. 100, no. 5, 2011, pp. 1866-78.
Dong Z, Hamid KA, Gao Y, et al. Polyamidoamine dendrimers can improve the pulmonary absorption of insulin and calcitonin in rats. J Pharm Sci. 2011;100(5):1866-78.
Dong, Z., Hamid, K. A., Gao, Y., Lin, Y., Katsumi, H., Sakane, T., & Yamamoto, A. (2011). Polyamidoamine dendrimers can improve the pulmonary absorption of insulin and calcitonin in rats. Journal of Pharmaceutical Sciences, 100(5), 1866-78. https://doi.org/10.1002/jps.22428
Dong Z, et al. Polyamidoamine Dendrimers Can Improve the Pulmonary Absorption of Insulin and Calcitonin in Rats. J Pharm Sci. 2011;100(5):1866-78. PubMed PMID: 21374620.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polyamidoamine dendrimers can improve the pulmonary absorption of insulin and calcitonin in rats. AU - Dong,Zhengqi, AU - Hamid,Khuriah Abdul, AU - Gao,Yang, AU - Lin,Yulian, AU - Katsumi,Hidemasa, AU - Sakane,Toshiyasu, AU - Yamamoto,Akira, Y1 - 2010/12/28/ PY - 2010/08/04/received PY - 2010/10/05/revised PY - 2010/11/09/accepted PY - 2011/3/5/entrez PY - 2011/3/5/pubmed PY - 2011/6/15/medline SP - 1866 EP - 78 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 100 IS - 5 N2 - 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. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/21374620/Polyamidoamine_dendrimers_can_improve_the_pulmonary_absorption_of_insulin_and_calcitonin_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(15)32178-X DB - PRIME DP - Unbound Medicine ER -