徐放性抗腫瘍剤カプセルの研究 - 前立腺腫瘍内埋め込み法の基礎的検討 -

Abstract

The properties and usefulness of a new anti-cancer drug capsule are reported. To make this capsule, anti-cancer drugs were entrapped in a polymer matrix made by radiation-induced polymerization at a low temperature using glass-forming monomers. This capsule was characterized by its stable and high biological activities, easy shaping into various forms and sizes and easy control of its release function. To test the clinical application of interstitial implantation of this capsule to locally advanced prostatic cancer, bullet-shaped capsules entrapping 16 mg and 31 mg of adriamycin were prepared and implanted into the bilateral lobes of the prostates of dogs. The total dosages of ADM were 32 mg and 62 mg. As the control, 32 mg of non-capsulated ADM was injected into the prostate. To check for any harmful effect on the tissue of the polymer matrix used to entrap ADM, polymer matrices with the same shape but not containing ADM were implanted into the prostate. In the capsule and polymer matrix groups, all the dogs were alive during the experimental period (capsule: 35 days, polymer: 60 days). In the injection group, two dogs died one and four days after the injection. In the 32 mg-ADM capsule group, plasma ADM levels were 0.02-0.12 mcg/ml from 30 min to 35 days after implantation and no peak levels were observed. In the 62 mg-ADM capsule group, plasma ADM levels were 0.03-0.1l mcg/ml during the same period. The implanted ADM was excreted into the urine at a constant rate for 48 hours after implantation in both groups. The plasma ADM levels in the injection group were higher than those in the capsule group, and peak levels were observed at 30 min after injection. The injected ADM was completely excreted into the urine within 4 hours after injection. Microscopic findings of the prostate in the capsule group showed thin layer necrosis around the capsule and wide interstitial edema and epithelial degeneration of the gland. In the injection group, necrosis and hemorrhage were observed. In the polymer matrix group, the surrounding prostatic tissue of the polymer was almost normal, although mild degree of round cell infiltration was observed in a limited portion adjacent to the polymer. These results proved that there is a constant slow release of ADM from the capsule in vivo. Further more, capsule implantation directly into tumor sites may result in greater effectiveness and less systemic toxity.