A semisynthetic Quillaja saponin as a drug delivery agent for aminoglycoside antibiotics.
OBJECTIVE
The purpose of this study was to investigate the utility of a purified, semisynthetic saponin, DS-1, prepared by deacylation of a naturally occurring saponin from the bark of the Quillaja saponaria Molina tree, as a permeation enhancer for mucosal delivery of the aminoglycosides, gentamicin and tobramycin.


METHODS
Gentamicin or tobramycin formulations, with and without DS-1, were administered to rats nasally, ocularly, and rectally. Serum aminoglycoside levels following mucosal application were compared with those administered intramuscularly. Gentamicin formulations, with and without DS-1, were administered intranasally to mice 60 minutes after a lethal bacterial challenge. To ascertain nasal irritation potential, DS-1 nosedrops were administered to rats twice daily for 7 days in the right nostril only. Comparison of the left (internal control) and right nostril was made with a control group that received only buffer.


RESULTS
Significant transport across mucous membranes was only observed in formulations containing DS-1. This effect on drug delivery was transient. Administration of an intranasal gentamicin/DS-1 formulation reversed the lethal bacterial challenge in mice, demonstrating that biological activity was retained after absorption. Nasal irritation was not observed in groups receiving DS-1 nosedrops, which were identical to control groups.


CONCLUSIONS
DS-1 has potential as a transmucosal delivery agent for the aminoglycoside antibiotics.
Recchia
J
J
Cambridge Biotech Corporation, Worcester, Massachusetts 01605-2376, USA.
Lurantos
M H
MH
Amsden
J A
JA
Storey
J
J
Kensil
C R
CR
D000617:Aminoglycosides / Q000493:pharmacokinetics*; D000818:Animals; D016503:Drug Delivery Systems; D005839:Gentamicins / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000378:metabolism*; D014031:Tobramycin / Q000097:blood
D000617:Aminoglycosides; D005839:Gentamicins; D012503:Saponins; D014031:Tobramycin