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 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.
Kortesuo
P
P
Orion Corporation, Orion Pharma, Pharmaceutical Development Department, Turku, Finland. pirjo.kortesuo@orion.fi
Ahola
M
M
Karlsson
S
S
Kangasniemi
I
I
Yli-Urpo
A
A
Kiesvaara
J
J
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D005260:Female; D005782:Gels; D020007:Implants, Experimental; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000737:chemistry; D014018:Tissue Distribution; D017312:Toremifene / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014316:Tritium; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D005782:Gels; D020845:Selective Estrogen Receptor Modulators; D014316:Tritium; D012822:Silicon Dioxide; D017312:Toremifene