Prolonged cytotoxic effect of colchicine released from biodegradable microspheres

Muvaffak, A
Gurhan, I
Hasırcı, Nesrin
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.


Synthesis of poly (dl-lactic-co-glycolic acid) coated magnetic nanoparticles for anti-cancer drug delivery
Tansık, Gülistan; Gündüz, Ufuk; Department of Biology (2012)
One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an extern...
Reversal of breast cancer resistance protein mediated multidrug resistance in MCF7 breast adenocarcinoma cell line
Urfalı, Çağrı; Gündüz, Ufuk; Department of Biology (2011)
Resistance to various chemotherapeutic agents is a major problem in success of cancer chemotherapy. One of the primary reasons of development of multidrug resistance (MDR) is the overexpression of ATP binding cassette (ABC) transporter proteins. Breast cancer resistance protein (BCRP) belongs to ABC transporter family and encoded by ABCG2 gene. BCRP is mainly expressed in MDR1 (P-glycoprotein) lacking breast cancer cells. Overexpression of BCRP leads to efflux of chemotherapeutic agents at higher rates, the...
Investigaton of chemopreventive properties of Urtica Dioica L., in MCF-7 and MDA231 breast cancer cell lines
Güler, Elif; İşcan, Mesude; Department of Biology (2011)
Cancer is a major health problem in developing world with mostly unsufficient treatment. Cancer prevention through dietary modification appears to be a practical and cost effective possibility. The aim of present study is to investigate the chemical components of “Urtica diocia,L (U. diocia) grown in Turkey” and the possible protective potential of its aqueous extract against breast cancer cell lines. U. diocia was extracted by maceration method which was performed for 6,12, 24, and 36 hours, at 50°C, 37°C,...
Expression analysis of TOP2A, MSH2 and MLH1 genes in MCF7 cells at different levels of etoposide resistance
Kaplan, Esra; Gündüz, Ufuk (2012-02-01)
Purpose: Development of resistance against anti-cancer drugs is one of the major obstacles of chemotherapy in the treatment of cancer. Etoposide is a topoisomerase II alpha (TOP2A) inhibitor, which is used in the treatment of breast cancer. Alterations in the expression of drug targets or DNA repair genes are among the important resistance mechanisms against TOP2A inhibitors. In this study, expression changes in TOP2A gene and two important mismatch repair (MMR) genes MSH2 and MLH1 were examined in order to...
GST isoenzymes in matched normal and neoplastic breast tissue
OĞUZTÜZÜN, SERPİL; Abu-Hijleh, A.; ÇOBAN, TÜLAY; Bulbul, D.; KILIÇ, MURAT; İŞCAN, Mümtaz; İşcan, Mesude (AEPress, s.r.o., 2011-01-01)
The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore we investigated GST activity and the protein expression of glutathione S-transferases (GSTs) isoenzymes known to be involved in the metabolism of endogenous and exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression.
Citation Formats
A. Muvaffak, I. Gurhan, and N. Hasırcı, “Prolonged cytotoxic effect of colchicine released from biodegradable microspheres,” JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, pp. 295–304, 2004, Accessed: 00, 2020. [Online]. Available: