The effect of cyclodextrins on the stability of peptides in nasal enzymic systems.

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 (t1/2 12 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 approximately 44 min to approximately 75 min in the presence of a 25-fold excess of beta-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.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Irwin WJ,Dwivedi AK,Holbrook PA,Dey MJ

doi

10.1023/a:1018946829225

subject

Has Abstract

pub_date

1994-12-01 00:00:00

pages

1698-703

issue

12

eissn

0724-8741

issn

1573-904X

journal_volume

11

pub_type

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