Kortesuo P, Ahola M, Karlsson S, Kangasniemi I, Yli-Urpo A, Kiesvaara J
Orion Corporation, Orion Pharma, Pharmaceutical Development Department, Turku, Finland.
Biomaterials. 2000 Jan;21(2):193-8. doi: 10.1016/s0142-9612(99)00148-9.
The purpose of the present study was to examine controlled delivery of toremifene citrate from subcutaneously implanted silica xerogel carrier and to evaluate silica xerogel related tissue effects after implantation. Toremifene citrate was incorporated into hydrolyzed silica sol in a room temperature process. Toremifene citrate treated silica xerogel implants were tested both in vitro and in vivo using healthy mice. Silica xerogel with tritium-labelled toremifene was implanted subcutaneously in mice for 42 d. To determine the amount of tritiated toremifene remaining in the silica discs at the implantation site, the discs were excised periodically and radioactivity measured. The amount of tritiated toremifene in the implant after 42 d was still about 16% and the amount of silica xerogel about 25%. In a histopathological study silica xerogel did not show any tissue irritation at the site of the implantation. A fibrotic capsule was formed around the implant. No silica xerogel related histological changes in liver, kidney, lymph nodes and uterus were observed during the implantation period. The silica xerogel discs showed a sustained release of toremifene citrate over 42 d. Histologically, toremifene-related changes in the uterus were also detectable at all studied time points. These findings suggest that silica xerogel is a promising carrier material for implantable controlled drug delivery system.
本研究的目的是检测皮下植入的硅胶干凝胶载体对枸橼酸托瑞米芬的控释效果，并评估植入后硅胶干凝胶对组织的影响。在室温条件下，将枸橼酸托瑞米芬加入水解硅溶胶中。使用健康小鼠对经枸橼酸托瑞米芬处理的硅胶干凝胶植入物进行体外和体内测试。将含有氚标记枸橼酸托瑞米芬的硅胶干凝胶皮下植入小鼠体内42天。为了确定植入部位硅胶圆片中剩余的氚标记枸橼酸托瑞米芬的量，定期切除圆片并测量放射性。42天后，植入物中氚标记枸橼酸托瑞米芬的量仍约为16%，硅胶干凝胶的量约为25%。在组织病理学研究中，硅胶干凝胶在植入部位未显示任何组织刺激。植入物周围形成了一层纤维囊。在植入期间，未观察到硅胶干凝胶对肝脏、肾脏、淋巴结和子宫的组织学变化。硅胶干凝胶圆片在42天内显示出枸橼酸托瑞米芬的持续释放。在组织学上，在所有研究时间点均能检测到子宫中与托瑞米芬相关的变化。这些发现表明，硅胶干凝胶是一种有前景的可植入控释药物递送系统的载体材料。
