Silica xerogel as an implantable carrier for controlled drug delivery - evaluation of drug distribution and tissue effects after implantation

The purpose of the present study was to examine controlled delivery of tore mifene citrate from subcutaneously implanted silica xerogel carrier and to evaluate silica xerogel related tissue effects after implantation. Toremife ne citrate was incorporated into hydrolyzed silica sol in a room temperatur e process. Toremifene citrate treated silica xerogel implants were tested b oth in vitro and in vivo using healthy mice. Silica xerogel with tritium-la belled toremifene was implanted subcutaneously in mice for 42 d. To determi ne the amount of tritiated toremifene remaining in the silica discs at the implantation site, the discs were excised periodically and radioactivity me asured. The amount of tritiated toremifene in the implant after 42 d was st ill about 16% and the amount of silica xerogel about 25%. In a histopatholo gical study silica xerogel did not show any tissue irritation at the site o f the implantation. ii fibrotic capsule was formed around the implant. No s ilica xerogel related histological changes in liver, kidney, lymph nodes an d uterus were observed during the implantation period. The silica xerogel d iscs showed a sustained release of toremifene citrate over 42 d. Histologic ally, toremifene-related changes in the uterus were also detectable at all studied time points. These findings suggest that silica xerogel is a promis ing carrier material for implantable controlled drug delivery system. (C) 1 999 Elsevier Science Ltd. All rights reserved.