J. Recchia et al., A SEMISYNTHETIC QUILLAJA SAPONIN AS A DRUG-DELIVERY AGENT FOR AMINOGLYCOSIDE ANTIBIOTICS, Pharmaceutical research, 12(12), 1995, pp. 1917-1923
Purpose. The purpose of this study was to investigate the utility of a
purified, semisynthetic saponin, DS-1, prepared by deacylation of a n
aturally occurring saponin from the bark of the Quillaja saponaria Mol
ina tree, as a permeation enhancer for mucosal delivery of the aminogl
ycosides, gentamicin and tobramycin. Methods. Gentamicin or tobramycin
formulations, with and without DS-1, were administered to rats nasall
y, ocularly, and rectally. Serum aminoglycoside levels following mucos
al application were compared with those administered intramuscularly.
Gentamicin formulations, with and without DS-1, were administered intr
anasally to mice 60 minutes after a lethal bacterial challenge. To asc
ertain 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. T
his effect on drug delivery was transient. Administration of an intran
asal gentamicin/DS-1 formulation reversed the lethal bacterial challen
ge 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.