Improvement of Nasal Bioavailability of Luteinizing Hormone-Releasing Hormone Agonist, Buserelin, by Cyclodextrin Derivatives in Rats
Autor: | Kaneto Uekama, Kazuya Abe, Kazutaka Matsubara, Tetsumi Irie |
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Rok vydání: | 1995 |
Předmět: |
Male
Agonist medicine.medical_specialty Cell Membrane Permeability Antineoplastic Agents Hormonal medicine.drug_class Biological Availability Pharmaceutical Science Mucous membrane of nose Absorption (skin) Peptide hormone Buserelin Absorption Excipients Gonadotropin-Releasing Hormone Internal medicine otorhinolaryngologic diseases medicine Animals Rats Wistar Administration Intranasal Cyclodextrins Chemistry respiratory system Rats Bioavailability Nasal Mucosa Nasal Absorption Spectrometry Fluorescence Endocrinology Nasal administration medicine.drug |
Zdroj: | Journal of Pharmaceutical Sciences. 84:1295-1300 |
ISSN: | 0022-3549 |
DOI: | 10.1002/jps.2600841108 |
Popis: | The effects of chemically modified cyclodextrins on the nasal absorption of buserelin, an agonist of luteinizing hormone-releasing hormone, were investigated in anesthetized rats. Of the cyclodextrins tested, dimethyl-beta-cyclodextrin (DM-beta-CyD) was the most effective in improving the rate and extent of the nasal bioavailability of buserelin. Fluorescence spectroscopic studies indicated that the cyclodextrins formed inclusion complexes with buserelin, which may reduce the diffusibility of buserelin across the nasal epithelium and may participate in the protection of the peptide against enzymatic degradation in the nasal mucosa. Additionally, the cyclodextrins increased the permeability of the nasal mucosa, which was the primary determinant based on the multiple regression analysis of the nasal absorption enhancement of buserelin. Scanning electron microscopic observations revealed that DM-beta-CyD induced no remarkable changes in the surface morphology of the nasal mucosa at a minimal concentration necessary to achieve substantial absorption enhancement. The present results suggest that DM-beta-CyD could improve the nasal bioavailability of buserelin and is well-tolerated by the nasal mucosa of the rat. |
Databáze: | OpenAIRE |
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