Recchia J, Lurantos M H, Amsden J A, Storey J, Kensil C R
Cambridge Biotech Corporation, Worcester, Massachusetts 01605-2376, USA.
Pharm Res. 1995 Dec;12(12):1917-23. doi: 10.1023/a:1016235705448.
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.
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.
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.
DS-1 has potential as a transmucosal delivery agent for the aminoglycoside antibiotics.
本研究旨在探讨一种纯化的半合成皂苷DS - 1的效用，该皂苷是通过对来自皂树（Quillaja saponaria Molina）树皮的天然皂苷进行脱酰基反应制备而成，作为氨基糖苷类药物庆大霉素和妥布霉素黏膜给药的渗透促进剂。
将含有和不含有DS - 1的庆大霉素或妥布霉素制剂经鼻、眼和直肠给予大鼠。将黏膜给药后血清氨基糖苷类药物水平与肌内给药后的水平进行比较。在致死性细菌攻击60分钟后，将含有和不含有DS - 1的庆大霉素制剂经鼻给予小鼠。为确定鼻刺激潜力，仅在大鼠右鼻孔每日两次给予DS - 1滴鼻剂，持续7天。将左侧（内部对照）和右侧鼻孔与仅接受缓冲液的对照组进行比较。
仅在含有DS - 1的制剂中观察到药物显著透过黏膜。这种对药物递送的作用是短暂的。经鼻给予庆大霉素/DS - 1制剂可逆转小鼠的致死性细菌攻击，表明吸收后生物活性得以保留。接受DS - 1滴鼻剂的组未观察到鼻刺激，这些组与对照组相同。
DS - 1有潜力作为氨基糖苷类抗生素的经黏膜给药载体。
