Abstract
α-Aminoboronic acid derivatives, potent and reversible inhibitors of aminopeptidases, were tested nasally in situ in rats for stabilizing externally administered peptides. These inhibitors, at nanomolar concentrations, were found to inhibit greatly the degradation of the model peptide, leucine-enkephalin (Leu-enk), in the nasal perfusate. Enzyme inhibition was greater with boroleucine and borovaline than that observed with boroalanine. Boroleucine was more than 100 times more effective in enzyme inhibition than bestatin and more than 1000 times more effective than puromycin.
Similar content being viewed by others
REFERENCES
S. T. Anik, G. McRae, C. Nerenberg, A. Worden, J. Foreman, J. Hwang, S. Kushinsky, R. E. Jones, and B. Vickery. J. Pharm. Sci. 73:684–685 (1984).
A. C. Moses, G. S. Gordon, M. C. Carey, and J. S. Flier. Diabetes 32:1040–1047 (1983).
M. Ishida, Y. Machida, N. Nambu, and T. Nagai. Chem. Pharm. Bull. 29:810–816 (1981).
T. Nishihata, S. Kim, S. Morishita, A. Kamada, N. Yata, and T. Higuchi. J. Pharm. Sci. 72:280–285 (1983).
S. Yoshioka, L. Caldwell, and T. Higuchi. J. Pharm. Sci. 71:593–594 (1982).
H. Okada, I. Yamazaki, Y. Ogawa, S. Hirai, T. Yoshiki, and H. J. Mima. J. Pharm. Sci. 71:1367–1371 (1982).
S. Hirai, T. Ikenaga, and T. Matsuzawa. Diabetes 27:296–299 (1978).
S. Hirai, T. Yashiki, and H. Mima. Int. J. Pharm. 9:173–184 (1981).
S. Hirai, T. Yashiki, and H. Mima. Int. J. Pharm. 9:165–172 (1981).
A. Hussain, J. Faraj, A. Yukihiko, and J. E. Truelove. Biochem. Biophys. Res. Commun. 133:923–928 (1985).
R. E. Stratford, Jr., and V. H. L. Lee. Int. J. Pharm. 30:73–82 (1986).
K. A. Koehler and G. E. Leinhard. Biochemistry 10:2477–2483 (1971).
M. Philipp and M. L. Bender. Proc. Natl. Acad. Sci. USA 68:478–480 (1971).
A. B. Shenvi. Biochemistry 25:1286–1291 (1986).
H. Suda, T. Aoyagi, T. Takeuchi, and H. Umezawa. Arch. Biochem. Biophys. 177:196–200 (1976).
J. K. McDonald, T. J. Reilly, and S. Ellis. Biochem. Biophys. Res. Commun. 16:135–140 (1964).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hussain, M.A., Shenvi, A.B., Rowe, S.M. et al. The Use of α-Aminoboronic Acid Derivatives to Stabilize Peptide Drugs During Their Intranasal Absorption. Pharm Res 6, 186–189 (1989). https://doi.org/10.1023/A:1015949013644
Issue Date:
DOI: https://doi.org/10.1023/A:1015949013644