In vitro release of cytotoxic nucleoside analogs from lactide-caprolactone and lactide-glycolide copolymers.

• Authors: Tomasz Kryczka , Maciej Bero , Janusz Kasperczyk , Piotr Dobrzyński , Barbara Marciniec , Maria Popierzal-Brzezińska , Paweł Grieb
• Languages of publication: EN

Abstracts

EN

The aims of our study were to assess the release of cytotoxic nucleoside analogs 5-fluorouracil and 2-chloro-2'-deoxyadenosine from different lactide-glycolide or lactide-caprolactone biodegradable copolymers and the effects of sterilization on this release. The polymers were sterilized either with ethylene oxide at 37°C, or with gamma radiation (15 kGy, 20 kGy, or 25 kGy). The kinetics of nucleoside release from the copolymers were measured over 50 days. Four copolymers exhibited relatively constant release of nucleosides in micromolar concentrations during the entire observation period. Sterilization with either ethylene oxide or gamma radiation only slightly influenced nucleoside release. Further development of these copolymers as an intracerebral nucleoside delivery system for local treatment of brain tumors is indicated.

Keywords

EN

sterilization; cladribine; 5-fluorouracil; biodegradable copolymers

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2002
• Volume: 49
• Issue: 1
• Pages: 205-210

Dates

published

2002

received

2001-09-10

revised

2001-12-2

accepted

2002-02-19

Contributors

author

Tomasz Kryczka

• Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

author

Maciej Bero

• Institute of Polymer Chemistry Polish Academy of Sciences, Zabrze, Poland

author

Janusz Kasperczyk

• Institute of Polymer Chemistry Polish Academy of Sciences, Zabrze, Poland

author

Piotr Dobrzyński

• Institute of Polymer Chemistry Polish Academy of Sciences, Zabrze, Poland

author

Barbara Marciniec

• Department of Pharmaceutical Chemistry, Karol Marcinkowski University of Medical Sciences, Poznań, Poland

author

Maria Popierzal-Brzezińska

• Department of Pharmaceutical Chemistry, Karol Marcinkowski University of Medical Sciences, Poznań, Poland

author

Paweł Grieb

• Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

References

• 1. Kornblith, P.L. & Walker, M. (1988) Chemotherapy for malignant gliomas. J. Neurosurg. 68, 1-17.
• 2. Laws, E.R. & Shaffrey, M.E. (1999) The inherent invasiveness of cerebral gliomas: Implications for clinical management. Int. J. Dev. Neurosci. 17, 413-420.
• 3. Matyja, E., Grieb, P., Ryba, M., Jagielski, J. & Mossakowski, M.J. (1996) Mitochondrial damage following exposure of organotypic cultures of human malignant gliomas to 2-chloro- and 2-bromo-2' -deoxyadenosine. Folia Neuropathol. 34, 31-39.
• 4. Grieb, P., Skierski, J., Jagielski, J., Ryba, M. & Mossakowski, M.J. (1995) DNA protein flow cytometry of dissociated cultures of human anaplastic gliomas. Pattern of proliferation and differentiation, and the effect of a new cytostatic drug cladribine (2-CdA). Folia Neuropathol. 33, 145-152.
• 5. Ceruti, S., Franceschi, C., Barbieri, D., Malorni, W., Camurri, A., Giammarioli, A.M., Ambrosini, A., Racagni, G., Cattabeni, F. & Abbracchio, M.P. (2000) Apoptosis induced by 2-chloro-adenosine and 2-chloro-2' -deoxyadenosine in a human astrocytoma cell line: Differential mechanisms and possible clinical relevance. J. Neurosci. Res. 60, 388-400.
• 6. Yamada, M., Nakagawa, H., Fukushima, M., Shimizu, K., Hayakawa, T. & Ikenaka, K. (1998) In vitro study on intrathecal use of 5-fluoro-2' -deoxyuridine (FdUrd) for meningeal dissemination of malignant brain tumors. J. Neurooncol. 37, 115-121.
• 7. Bogdahn, U., Weber, H., Zapf, J., Dunisch, G., Lobering, H.G. & Mertens, H.G. (1987) Therapy of malignant brain tumors: Comparison of the in vitro activities of vidarabin-monophosphate, BCNU and 5-fluorouracil. Acta Neurol. Scand. 75, 28-36.
• 8. Menei, P., Venier, M.C., Gamelin, E., Saint- Andre, J.P., Hayek, G., Jadaud, E., Fournier, D., Mercier, P., Guy, G. & Benoit, J.P. (1999) Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma. Cancer 86, 325-330.
• 9. Kryczka, T., Grieb, P., Bero, M., Kasperczyk, J. & Dobrzynski, P. (2000) Kinetics of nucleoside release from lactidecaprolactone and lactide- glycolide polymers in vitro. Acta Biochim. Polon. 47, 59-64.
• 10. Yuan, X., Fahlman, C., Tabassi, K. & Williams, J.A. (1999) Synthetic, implantable, biodegradable polymers for controlled release of radiosensitizer. Cancer Biother. Radiopharmaceut. 14, 177-186.
• 11. Wahlberg, L.U., Almquist, P.M., Glantz, M.J. & Boethius, J. (1996) Polymeric controlled-release amsacrine chemotherapy in an experimental glioma model. Acta Neurochir. 138, 1323-1330.
• 12. Bero, M., Dobrzynski, P. & Kasperczyk, J. (2000) Copolymerization of glycolide with lactide and εcaprolactone in the presence of initiators containing Li, Mg and Ca. Polymers in Medicine and Surgery, PIMS 2000 International Conference Pre-Prints; pp. 390-396, Danube Uniwersity, Published by IOM Communcations Ltd. The Cameleon Press Limited.
• 13. Bero, M., Adamus, G., Kasperczyk, J. & Janeczek, H. (1993) Synthesis of block copolymers elipson-caprolactone and lactide in the presence of lithium t-butoxide. Polymer Bulletin 31, 9-14.
• 14. Dobrzynski, P., Kasperczyk, J. & Bero, M. (2000) Synthesis and properties of biodegradable copolymers (PLAGA, PGACap, PLACap) obtained in the presence of new low toxic initiators containing zircon; Polymers in Medicine and Surgery, PIMS 2000 Conference Pre-Prints, pp. 381-389, Danube University, Published by IOM Communcations Ltd. The Cameleon Press Limited.
• 15. Dobrzynski, P., Kasperczyk, J., Janeczek, H. & Bero, M. (2001) Synthesis of biodegradable copolymers with the use of low toxic zirconium compounds. Copolymerization of glycolide with L -lactide initiated by Zr(acac)4 Macromolecules 34, 5090-5099. Pharmacopoea Polonica (1996) Edn. V, vol. 2, Polish Pharmaceutical Society, Warsaw.
• 16. Rajkumar, S.V., Burch, P.A., Nair, S., Dinapoli, R.P., Scheithauer, B., O’Fallon, J., Etzell, P.S., Leitch, J.M., Morton, R.F. & Marks, R.S. (1999) Phase II north central cancer treatment group study of 2-chlorodeoxyadenosine in patients with recurrent glioma. Am. J. Clin. Oncol. 22, 168-171.
• 17. Hoshino, T. & Wilson, C.B. (1979) Cell kinetic analyses of human malignant brain tumors (gliomas). Cancer 44, 956-962.
• 18. Yuan, X., Dillehay, L.E., Williams, J.R. & Williams, J.A. (2001) IUdR polymers for combined continuous low-dose rate and high-dose rate sensitization of experimental human malignant gliomas. Int. J. Cancer. 96, 118-125.