PURPOSE: 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.
PURPOSE: 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.
Authors: J Y Wu; B H Gardner; C I Murphy; J R Seals; C R Kensil; J Recchia; G A Beltz; G W Newman; M J Newman Journal: J Immunol Date: 1992-03-01 Impact factor: 5.422
Authors: M J Newman; J Y Wu; B H Gardner; K J Munroe; D Leombruno; J Recchia; C R Kensil; R T Coughlin Journal: J Immunol Date: 1992-04-15 Impact factor: 5.422