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The Effect of Cyclodextrins on the Stability of Peptides in Nasal Enzymic Systems

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Abstract

Leucine enkephalin (YGGFL) undergoes rapid degradation in sheep nasal mucosa to yield GGFL which is further degraded to FL. The activity of the nasal mucosal homogenate against YGGFL and GGFL (t1/212 and 7 min) was significantly greater than that observed with a nasal wash fluid (t1/2 40 and 13 min). The effect of cyclodextrins on the rate of degradation of FGG and YGGFL by leucine aminopeptidase (LAP) and of GGF by carboxypeptidase A (CPA) was monitored. Little effect was observed with FGG (with LAP) but the half-life of YGGFL (with LAP) was extended from ~44 min to ~75 min in the presence of a 25-fold excess of β-cyclodextrin. The stability of GGF (with CPA) was also enhanced; an effect was observable with a 5-fold excess of cyclodextrin and the half-life could be extended by 40–75%. An equation is presented which allows the estimation of the concentration of free peptide in the peptide-cyclodextrin solutions.

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Author notes

  1. Anil K. Dwivedi

    Present address: Pharmaceutical Division, Central Drug Research Institute, Lucknow, 226001, India

  2. Paula A. Holbrook

    Present address: , Morley Street, Loughborough, Leicestershire, LE11 1EP

Authors and Affiliations

  1. Drug Development Research Group, Pharmaceutical Sciences Institute, Department of Pharmaceutical and Biological Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK

    William J. Irwin, Anil K. Dwivedi & Paula A. Holbrook

  2. Fisons Pharmaceuticals, Fisons PLC, London Road, Holmes Chapel, CW4 8BE

    Michael J. Dey

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  1. William J. Irwin
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  3. Paula A. Holbrook
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  4. Michael J. Dey
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Irwin, W.J., Dwivedi, A.K., Holbrook, P.A. et al. The Effect of Cyclodextrins on the Stability of Peptides in Nasal Enzymic Systems. Pharm Res 11, 1698–1703 (1994). https://doi.org/10.1023/A:1018946829225

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