Sustained-release properties of microencapsulated mitomycin C with ethylcellulose infused into the renal artery of the dog.

Mitomycin C (MMC) was microencapsulated with ethylcellulose. The microcapsules contained, on average, 80% of biologically active MMC and had a sustained-release property. The mean particle size was 224 micrometers so that the microcapsules were readily infused into a canine kidney through arterial catheterization. Ex vivo infusion demonstrated that the microcapsules lodged in the small arteries, mainly at the cortico-medullary junction, and released concentrated MMC into the surrounding tissue. In vivo experiments revealed that the canine kidneys infused with the microcapsules retained active MMC for more than 6 hours and showed extensive necrosis five days after the infusion. The kidneyks infused with nonencapsulated MMC rapidly excreted MMC and showed mild histologic changes. The blood level of MMC released from the intrarenal microcapsules was markedly reduced as compared with control levels. The results suggest that the potential therapeutic effect of intraarterial infusion of MMC microcapsules is a function of embolization and prolonged drug action, and that selective infusion of MMC microcapsules into tumor-supplying arteries could facilitate intensive topical chemotherapy with minimum systemic side-effects.