A SEMISYNTHETIC QUILLAJA SAPONIN AS A DRUG-DELIVERY AGENT FOR AMINOGLYCOSIDE ANTIBIOTICS

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.