PURPOSE: To evaluate the feasibility of iontophoresis and the combination effects with chemical enhancers on in vivo hypocalcemic effect of transbuccally delivered salmon calcitonin (sCT). METHODS: N-acetyl-L-cysteine (NAC), sodium deoxyglycocholate (SDGC), and ethanol were used as chemical enhancers; and 0.5 mA/cm(2) fixed electric current was employed as a physical enhancer. sCT hydrogel was applied to rabbit buccal mucosa, and blood samples were obtained via the central auricular artery. Blood calcium level was measured by calcium kit and the conformational changes of buccal mucosa were investigated with FT-IR spectroscopy. Hematoxylin/eosin staining was used for the histological evaluation of buccal mucosa. RESULTS: Iontophoresis groups except iontophoresis-NAC group showed significant hypocalcemic effect compared to negative control, in particular iontophoresis-SDGC combination group showed fast onset of action as well as sustained hypocalcemic effect (p < 0.05). FT-IR result demonstrated the reduction of buccal barrier function, and the histological study showed a decrease in buccal thickness as well as minor damage to the dermal-epidermal junctions in the enhancing method groups; however, the damaged tissues virtually recovered within 24 h after the removal of electrodes. CONCLUSIONS: Iontophoresis and combination with SDGC were found to be safe and potential strategies for transbuccal peptide delivery in vivo.
PURPOSE: To evaluate the feasibility of iontophoresis and the combination effects with chemical enhancers on in vivo hypocalcemic effect of transbuccally delivered salmon calcitonin (sCT). METHODS:N-acetyl-L-cysteine (NAC), sodium deoxyglycocholate (SDGC), and ethanol were used as chemical enhancers; and 0.5 mA/cm(2) fixed electric current was employed as a physical enhancer. sCT hydrogel was applied to rabbit buccal mucosa, and blood samples were obtained via the central auricular artery. Blood calcium level was measured by calcium kit and the conformational changes of buccal mucosa were investigated with FT-IR spectroscopy. Hematoxylin/eosin staining was used for the histological evaluation of buccal mucosa. RESULTS: Iontophoresis groups except iontophoresis-NAC group showed significant hypocalcemic effect compared to negative control, in particular iontophoresis-SDGC combination group showed fast onset of action as well as sustained hypocalcemic effect (p < 0.05). FT-IR result demonstrated the reduction of buccal barrier function, and the histological study showed a decrease in buccal thickness as well as minor damage to the dermal-epidermal junctions in the enhancing method groups; however, the damaged tissues virtually recovered within 24 h after the removal of electrodes. CONCLUSIONS: Iontophoresis and combination with SDGC were found to be safe and potential strategies for transbuccal peptide delivery in vivo.
Authors: Ayyappa Chaturvedula; Dipty P Joshi; Carter Anderson; Russell L Morris; Walter L Sembrowich; Ajay K Banga Journal: Int J Pharm Date: 2005-06-13 Impact factor: 5.875
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