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Nitric oxide donors can enhance the intestinal transport and absorption of insulin and [Asu(1,7)]-eel calcitonin in rats.
J Control Release. 2005 Sep 02; 106(3):287-97.JC

Abstract

The characteristics of three NO donors, 3-(2-hydroxy-1-(1-methylethyl)-2-nitrosohydrazino)-1-propanamine (NOC5), N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC12) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) as absorption enhancers for peptide drugs were examined in rats using a modified Ussing chamber method and an in situ closed loop method. Insulin and [Asu(1,7)]-eel calcitonin (ECT) were used as a model drug to investigate the effectiveness of the tested enhancers. The NO donors significantly increased the in vitro permeability of insulin across all intestinal membranes. In general, the absorption enhancement effects of these NO donors were greater in the colon than those in the jejunum and ileum. Of these NO donors, SNAP was the most effective enhancer. Their effects were concentration-dependent over the range of 0.01 to 0.1 mM. However, 0.1 mM NO donors had almost the same effects as those at 1 mM concentration. The absorption-enhancing effects of the three NO donors were inhibited by the co-administration of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide, sodium salt (carboxy-PTIO), an NO scavenger, suggesting that NO might be responsible for the efficacy of NO donors. In the in situ closed loop experiments, the three enhancers significantly improved the pharmacological availability % (PA%) of insulin in the small and large intestine. Similar results were also obtained when NO donors were added to ECT solution by an in situ closed loop method. These results suggest that NO donors possess excellent effectiveness for the use as absorption enhancers of peptide drugs and they are very effective at lower concentrations compared to the conventional enhancers.

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 available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15982776

Citation

Fetih, Gihan, et al. "Nitric Oxide Donors Can Enhance the Intestinal Transport and Absorption of Insulin and [Asu(1,7)]-eel Calcitonin in Rats." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 106, no. 3, 2005, pp. 287-97.
Fetih G, Habib F, Okada N, et al. Nitric oxide donors can enhance the intestinal transport and absorption of insulin and [Asu(1,7)]-eel calcitonin in rats. J Control Release. 2005;106(3):287-97.
Fetih, G., Habib, F., Okada, N., Fujita, T., Attia, M., & Yamamoto, A. (2005). Nitric oxide donors can enhance the intestinal transport and absorption of insulin and [Asu(1,7)]-eel calcitonin in rats. Journal of Controlled Release : Official Journal of the Controlled Release Society, 106(3), 287-97.
Fetih G, et al. Nitric Oxide Donors Can Enhance the Intestinal Transport and Absorption of Insulin and [Asu(1,7)]-eel Calcitonin in Rats. J Control Release. 2005 Sep 2;106(3):287-97. PubMed PMID: 15982776.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nitric oxide donors can enhance the intestinal transport and absorption of insulin and [Asu(1,7)]-eel calcitonin in rats. AU - Fetih,Gihan, AU - Habib,Fawsia, AU - Okada,Naoki, AU - Fujita,Takuya, AU - Attia,Mohammed, AU - Yamamoto,Akira, PY - 2004/08/24/received PY - 2005/05/12/revised PY - 2005/05/16/accepted PY - 2005/6/29/pubmed PY - 2005/10/22/medline PY - 2005/6/29/entrez SP - 287 EP - 97 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 106 IS - 3 N2 - The characteristics of three NO donors, 3-(2-hydroxy-1-(1-methylethyl)-2-nitrosohydrazino)-1-propanamine (NOC5), N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC12) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) as absorption enhancers for peptide drugs were examined in rats using a modified Ussing chamber method and an in situ closed loop method. Insulin and [Asu(1,7)]-eel calcitonin (ECT) were used as a model drug to investigate the effectiveness of the tested enhancers. The NO donors significantly increased the in vitro permeability of insulin across all intestinal membranes. In general, the absorption enhancement effects of these NO donors were greater in the colon than those in the jejunum and ileum. Of these NO donors, SNAP was the most effective enhancer. Their effects were concentration-dependent over the range of 0.01 to 0.1 mM. However, 0.1 mM NO donors had almost the same effects as those at 1 mM concentration. The absorption-enhancing effects of the three NO donors were inhibited by the co-administration of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide, sodium salt (carboxy-PTIO), an NO scavenger, suggesting that NO might be responsible for the efficacy of NO donors. In the in situ closed loop experiments, the three enhancers significantly improved the pharmacological availability % (PA%) of insulin in the small and large intestine. Similar results were also obtained when NO donors were added to ECT solution by an in situ closed loop method. These results suggest that NO donors possess excellent effectiveness for the use as absorption enhancers of peptide drugs and they are very effective at lower concentrations compared to the conventional enhancers. SN - 0168-3659 UR - https://www.unboundmedicine.com/medline/citation/15982776/Nitric_oxide_donors_can_enhance_the_intestinal_transport_and_absorption_of_insulin_and_[Asu_17_]_eel_calcitonin_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-3659(05)00240-3 DB - PRIME DP - Unbound Medicine ER -