toremifene and Foreign-Body-Reaction

Sol-gel-processed sintered silica xerogel was studied as a controllable, dissolvable, implantable material. The erosion of the matrix and the release of the preadsorbed drug toremifene citrate was investigated both in vitro and in vivo using mice. In an in vitro dissolution study, 50 to 60% of the drug was released after 24 h, according to the square root of time kinetics, and the weight loss of the silica was 24 wt %. Silica xerogel with tritium-labeled toremifene was implanted subcutaneously in mice for 56 days. To determine the amount of tritiated drug remaining in the silica disks at the implantation site, the disks were excised periodically and the radioactivity measured. About 40% of the radioactivity was released during the first 4 days and all of it within 28 days. Radioactivity also was measured in the liver, lungs, kidneys, uterus, and blood. The radioactivity reached a maximum level after 4 days in the liver, kidneys, and lungs and slowly decreased until all of the drug had been released from the matrix after 28 days. After release of the drug (28 days) the amount of remaining silica xerogel implant was 45 wt %, and at the end of the study (56 days) it was 24 wt %. In the histopathological study, sintered silica xerogel did not show any tissue toxicity at the site of the implantation, in the liver, or in the kidneys. It was concluded that sintered silica xerogel is a biocompatible and controllably resorbable material and therefore is a promising matrix for use in the sustained delivery of drugs.

Topics: Animals; Biocompatible Materials; Drug Carriers; Drug Delivery Systems; Drug Implants; Female; Foreign-Body Reaction; Gels; Materials Testing; Mice; Mice, Inbred DBA; Silicon Dioxide; Toremifene; Tritium