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Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats.
J Control Release. 2011 Jan 05; 149(1):21-8.JC

Abstract

Effects of polyamidoamine (PAMAM) dendrimers on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF), fluorescein isothiocyanate-dextrans (FDs) with various molecular weights, calcitonin and insulin were used as model drugs of poorly absorbable drugs. The absorption of CF, FD4 and calcitonin from the rat small intestine was significantly enhanced in the presence of PAMAM dendrimers. The absorption-enhancing effects of PAMAM dendrimers for improving the small intestinal absorption of CF were concentration and generation dependent and a maximal absorption-enhancing effect was observed in the presence of 0.5% (w/v) G2 PAMAM dendrimer. However, G2 PAMAM dendrimer had almost no absorption-enhancing effect on the small intestinal absorption of macromolecular drugs including FD10 and insulin. Overall, the absorption-enhancing effects of G2 PAMAM dendrimer in the small intestine decreased as the molecular weights of drug increased. However, G2 PAMAM dendrimer did not enhance the intestinal absorption of these drugs with different molecular weights in the large intestine. Furthermore, we evaluated the intestinal membrane damage with or without G2 PAMAM dendrimer. G2 PAMAM dendrimer (0.5% (w/v)) significantly increased the activities of lactate dehydrogenase (LDH) and the amounts of protein released from the intestinal membranes, but the activities and amounts of these toxic markers were less than those in the presence of 3% Triton X-100 used as a positive control. Moreover, G2 PAMAM dendrimer at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the activities and amounts of these toxic markers. These findings suggested that PAMAM dendrimers at lower concentrations might be potential and safe absorption enhancers for improving absorption of poorly absorbable drugs from the small intestine.

Authors+Show Affiliations

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

20184931

Citation

Lin, Yulian, et al. "Polyamidoamine Dendrimers as Novel Potential Absorption Enhancers for Improving the Small Intestinal Absorption of Poorly Absorbable Drugs in Rats." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 149, no. 1, 2011, pp. 21-8.
Lin Y, Fujimori T, Kawaguchi N, et al. Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats. J Control Release. 2011;149(1):21-8.
Lin, Y., Fujimori, T., Kawaguchi, N., Tsujimoto, Y., Nishimi, M., Dong, Z., Katsumi, H., Sakane, T., & Yamamoto, A. (2011). Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats. Journal of Controlled Release : Official Journal of the Controlled Release Society, 149(1), 21-8. https://doi.org/10.1016/j.jconrel.2010.02.017
Lin Y, et al. Polyamidoamine Dendrimers as Novel Potential Absorption Enhancers for Improving the Small Intestinal Absorption of Poorly Absorbable Drugs in Rats. J Control Release. 2011 Jan 5;149(1):21-8. PubMed PMID: 20184931.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats. AU - Lin,Yulian, AU - Fujimori,Takeo, AU - Kawaguchi,Naoko, AU - Tsujimoto,Yuiko, AU - Nishimi,Mariko, AU - Dong,Zhengqi, AU - Katsumi,Hidemasa, AU - Sakane,Toshiyasu, AU - Yamamoto,Akira, Y1 - 2010/02/22/ PY - 2009/10/14/received PY - 2010/02/09/revised PY - 2010/02/12/accepted PY - 2010/2/27/entrez PY - 2010/2/27/pubmed PY - 2011/4/29/medline SP - 21 EP - 8 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 149 IS - 1 N2 - Effects of polyamidoamine (PAMAM) dendrimers on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF), fluorescein isothiocyanate-dextrans (FDs) with various molecular weights, calcitonin and insulin were used as model drugs of poorly absorbable drugs. The absorption of CF, FD4 and calcitonin from the rat small intestine was significantly enhanced in the presence of PAMAM dendrimers. The absorption-enhancing effects of PAMAM dendrimers for improving the small intestinal absorption of CF were concentration and generation dependent and a maximal absorption-enhancing effect was observed in the presence of 0.5% (w/v) G2 PAMAM dendrimer. However, G2 PAMAM dendrimer had almost no absorption-enhancing effect on the small intestinal absorption of macromolecular drugs including FD10 and insulin. Overall, the absorption-enhancing effects of G2 PAMAM dendrimer in the small intestine decreased as the molecular weights of drug increased. However, G2 PAMAM dendrimer did not enhance the intestinal absorption of these drugs with different molecular weights in the large intestine. Furthermore, we evaluated the intestinal membrane damage with or without G2 PAMAM dendrimer. G2 PAMAM dendrimer (0.5% (w/v)) significantly increased the activities of lactate dehydrogenase (LDH) and the amounts of protein released from the intestinal membranes, but the activities and amounts of these toxic markers were less than those in the presence of 3% Triton X-100 used as a positive control. Moreover, G2 PAMAM dendrimer at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the activities and amounts of these toxic markers. These findings suggested that PAMAM dendrimers at lower concentrations might be potential and safe absorption enhancers for improving absorption of poorly absorbable drugs from the small intestine. SN - 1873-4995 UR - https://www.unboundmedicine.com/medline/citation/20184931/Polyamidoamine_dendrimers_as_novel_potential_absorption_enhancers_for_improving_the_small_intestinal_absorption_of_poorly_absorbable_drugs_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-3659(10)00150-1 DB - PRIME DP - Unbound Medicine ER -