Tags

Type your tag names separated by a space and hit enter

Absorption enhancement of a protein drug by nitric oxide donor: effect on nasal absorption of human granulocyte colony-stimulating factor.
J Drug Target. 2000; 8(3):185-94.JD

Abstract

The objective of this study was to evaluate the effect of a nitric oxide (NO) donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), on the nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rabbits and to evaluate the irritation (cytotoxicity) potential of the NO donor on the mucosal membrane using a cultured cell system (strain KB, human epidermoid carcinoma of the floor of the mouth). Significantly higher serum G-CSF concentration and increased total leukocyte count in the peripheral blood were observed after coadministration of rhG-CSF (100 microg/kg) with SNAP at various doses (0.3-3.3 mg/kg). The serum G-CSF concentration and the increased total leukocyte count were markedly decreased by the presence of the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazole-1-oxyl 3-oxide sodium salt (carboxy-PTIO), in combination with rhG-CSF and SNAP. However, no significant inhibitory effect of glutathione (peroxynitrite scavenger) on the absorption-enhancing effect of SNAP was observed. These results suggest that carboxy-PTIO inhibits the absorption-enhancing effect of NO released from SNAP. We found that SNAP has a very low potential for cytotoxicity, as evaluated by the cell detachment assay, release of lactate dehydrogenase (LDH) from cultured cells and morphological observations of nasal tissue of rabbits. It is concluded that a NO donor such as SNAP is a promising absorption enhancer for nasal protein-drug delivery.

Authors+Show Affiliations

Department of Pharmaceutics, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida-shi, Tokyo 194-8543, Japan. watanabe@ac.shoyaku.ac.jpNo 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

10938528

Citation

Watanabe, Y, et al. "Absorption Enhancement of a Protein Drug By Nitric Oxide Donor: Effect On Nasal Absorption of Human Granulocyte Colony-stimulating Factor." Journal of Drug Targeting, vol. 8, no. 3, 2000, pp. 185-94.
Watanabe Y, Utoguchi N, Ishii A, et al. Absorption enhancement of a protein drug by nitric oxide donor: effect on nasal absorption of human granulocyte colony-stimulating factor. J Drug Target. 2000;8(3):185-94.
Watanabe, Y., Utoguchi, N., Ishii, A., Tai, Y., Shiota, H., Kurai, H., & Matsumoto, M. (2000). Absorption enhancement of a protein drug by nitric oxide donor: effect on nasal absorption of human granulocyte colony-stimulating factor. Journal of Drug Targeting, 8(3), 185-94.
Watanabe Y, et al. Absorption Enhancement of a Protein Drug By Nitric Oxide Donor: Effect On Nasal Absorption of Human Granulocyte Colony-stimulating Factor. J Drug Target. 2000;8(3):185-94. PubMed PMID: 10938528.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Absorption enhancement of a protein drug by nitric oxide donor: effect on nasal absorption of human granulocyte colony-stimulating factor. AU - Watanabe,Y, AU - Utoguchi,N, AU - Ishii,A, AU - Tai,Y, AU - Shiota,H, AU - Kurai,H, AU - Matsumoto,M, PY - 2000/8/12/pubmed PY - 2000/10/7/medline PY - 2000/8/12/entrez SP - 185 EP - 94 JF - Journal of drug targeting JO - J Drug Target VL - 8 IS - 3 N2 - The objective of this study was to evaluate the effect of a nitric oxide (NO) donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), on the nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rabbits and to evaluate the irritation (cytotoxicity) potential of the NO donor on the mucosal membrane using a cultured cell system (strain KB, human epidermoid carcinoma of the floor of the mouth). Significantly higher serum G-CSF concentration and increased total leukocyte count in the peripheral blood were observed after coadministration of rhG-CSF (100 microg/kg) with SNAP at various doses (0.3-3.3 mg/kg). The serum G-CSF concentration and the increased total leukocyte count were markedly decreased by the presence of the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazole-1-oxyl 3-oxide sodium salt (carboxy-PTIO), in combination with rhG-CSF and SNAP. However, no significant inhibitory effect of glutathione (peroxynitrite scavenger) on the absorption-enhancing effect of SNAP was observed. These results suggest that carboxy-PTIO inhibits the absorption-enhancing effect of NO released from SNAP. We found that SNAP has a very low potential for cytotoxicity, as evaluated by the cell detachment assay, release of lactate dehydrogenase (LDH) from cultured cells and morphological observations of nasal tissue of rabbits. It is concluded that a NO donor such as SNAP is a promising absorption enhancer for nasal protein-drug delivery. SN - 1061-186X UR - https://www.unboundmedicine.com/medline/citation/10938528/Absorption_enhancement_of_a_protein_drug_by_nitric_oxide_donor:_effect_on_nasal_absorption_of_human_granulocyte_colony_stimulating_factor_ L2 - https://www.tandfonline.com/doi/full/10.3109/10611860008996864 DB - PRIME DP - Unbound Medicine ER -