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Strategic Approaches for Enhancement of In Vivo Transbuccal Peptide Drug Delivery in Rabbits using Iontophoresis and Chemical Enhancers

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ABSTRACT

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/cm2 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.

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ACKNOWLEDGMENTS AND DISCLOSURES

The present research has been conducted by the Settlement Research Grant of Keimyung University.

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Authors and Affiliations

  1. Department of Smart Foods and Drugs, Graduate School, Inje University, 197 Inje-ro, Gimhae-si, Gyeongsangnam-Do, 621-749, Republic of Korea

    Dong-Ho Oh, Min-Ju Kim & Sang-Ok Jeon

  2. College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu, 704-701, Republic of Korea

    Dong-Ho Oh, Sang-Ok Jeon, Jo-Eun Seo & Sangkil Lee

  3. College of Pharmacy, Dongguk University, 32 Dongguk-ro, Goyang-si, Gyeonggi-Do, 410-820, Republic of Korea

    Seong-Hoon Jeong

  4. Graduate School of Transportation, Korea National University of Transportation, 157 Cheoldoparkmulgwan-ro, Uiwang-si, Gyeonggi-Do, 437-763, Republic of Korea

    Jeong-Won Kang

  5. Department of IT Convergence, Korea National University of Transportation, 50 Daehak-ro, Chungju-si, Chungcheongbuk-Do, 380-702, Republic of Korea

    Jeong-Won Kang

  6. College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 156-756, Republic of Korea

    Young-Wook Choi

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  1. Dong-Ho Oh
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Correspondence to Sangkil Lee.

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Oh, DH., Kim, MJ., Jeon, SO. et al. Strategic Approaches for Enhancement of In Vivo Transbuccal Peptide Drug Delivery in Rabbits using Iontophoresis and Chemical Enhancers. Pharm Res 32, 929–940 (2015). https://doi.org/10.1007/s11095-014-1507-z

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  • DOI: https://doi.org/10.1007/s11095-014-1507-z

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