The use of alpha-aminoboronic acid derivatives to stabilize peptide drugs during their intranasal absorption.
alpha-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.
Hussain
M A
MA
Du Pont Pharmaceuticals, Medical Products Department, Wilmington, Delaware 19880-0400.
Shenvi
A B
AB
Rowe
S M
SM
Shefter
E
E
D000281:Administration, Intranasal; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000378:metabolism; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew
D001897:Boronic Acids; D010455:Peptides; D004743:Enkephalin, Leucine; D000626:Aminopeptidases