Prolonged cytotoxic effect of colchicine released from biodegradable microspheres


Muvaffak A., Gurhan I., Hasirci N.

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, ss.295-304, 2004 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Basım Tarihi: 2004
  • Doi Numarası: 10.1002/jbm.b.30092
  • Dergi Adı: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
  • Sayfa Sayıları: ss.295-304

Özet

One the main problems of cancer chemotherapy is the unwanted damage to normal cells caused by the high toxicities of anticancer drugs. Any system of controlled drug delivery that would reduce the total amount of drug required, and thus reduce the side effects, would potentially help to improve chemotherapy. In this respect, biodegradable gelatin microspheres were prepared by water/oil emulsion polymerization and by crosslinking with glutaraldehyde (GTA) as the drug-carrier system. Microspheres were loaded with colchicine, a model antimitotic drug, which was frequently used as an antimitotic agent in cancer research involving cell cultures. Microsphere sizes, swelling and degradation properties, drug-release kinetics, and cytotoxities were studied. Swelling characteristics of microspheres changed upon changing GTA concentration. A decrease in swelling values was recorded as GTA crosslink density was increased. In vitro drug release in PBS (0.01M, pH 7.4) showed rapid colchicine release up to similar to83% (at t = 92 h) for microspheres with low GTA (0.05% v/v), whereas a slower release profile (only similar to39%) was obtained for microspheres with high GTA (0.50% v/v) content, for the same period. Cytotoxicity tests with MCF-7, HeLa and H-82 cancer cell lines showed that free colchicine was very toxic, showing an similar to100% lethal effect in both HeLa and H-82 cell lines and more than 50% decrease in viability in MCF-7 cells in 4 days. Indeed, entrapped colchicine indicated similar initial high toxic effect on cell viability in MCF-7 cell line and this effect became more dominant as colchicine continued to be released from microspheres in the same period. In conclusion, the control of the release rate of colchicine from gelatin microspheres was achieved under in vitro conditions by gelatin through the alteration of crosslinking conditions. Indeed, the results suggested the potential application of gelatin microspheres crosslinked with GTA as a sustained drug-delivery system for anticancer drugs for local chemotherapy administrations. (C) 2004 Wiley Periodicals, Inc.