Synthesis of semi-biodegradable crosslinked microspheres for the delivery of 1,25 dihydroxyvitamin D3 for the treatment of hepatocellular carcinoma

Nguyen, T. L. U., Tey, S. Y., Pourgholami, M. H., Morris, D. L., Davis, T. P., Barner-Kowollik, C., & Stenzel, M. H. (2007) Synthesis of semi-biodegradable crosslinked microspheres for the delivery of 1,25 dihydroxyvitamin D3 for the treatment of hepatocellular carcinoma. European Polymer Journal, 43(5).

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It has been demonstrated that 1,25 dihydroxyvitamin D3 (1,25(OH)2VD3) can inhibit the proliferation of cancer cells, including colorectal and hepatocellular cells which are mainly responsible for liver cancer. However, the use of 1,25(OH)2VD3 is hampered due to the development of hypercalcaemia. We hereby report a promising technique in liver cancer treatment by utilizing crosslinked microspheres prepared by polymerization as a carrier to control the release of 1,25(OH)2VD3 or hydrophobic drug in general at targeted sites over a long period. Microspheres in the size range of 35 μm were prepared and the drug was loaded to these poly(vinyl neodecanoate-crosslinked-ethyleneglycol dimethacrylate) microspheres after polymerization. The release study has shown that up to 1% of the drug was released after 40 days. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and direct contact cytotoxicity assay using HT-20 and L929 confirm the non-toxicity of these spheres. © 2007 Elsevier Ltd. All rights reserved.

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ID Code: 99158
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :8 Export Date: 5 September 2016 CODEN: EUPJA Correspondence Address: Stenzel, M.H.; Centre for Advanced Macromolecular Design (CAMD), School of Chemical Sciences and Engineering, University of New South Wales, Sydney, NSW 2052, Australia; email: References: Seong, J., Keum, K.C., Han, K.H., Lee, D.Y., Lee, J.T., Chon, C.Y., Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma (1999) Int J Radiat Oncol, 43, pp. 393-397; De Santics, T.J., Goldberg, N.S., Mueller, R.P., Percutaneous treatment of hepatic neoplasms: a review of current techniques (1998) Cardiovas Intervent Radiol, 21, pp. 273-296; Akhter, J., Chen, X., Bowrey, P., Bolton, E.J., Morris, D.L., Vitamin D3 analog EB 1089 inhibits growth of subcutaneous xenografts of human colon cancer cell line LoVo in a nude mouse mode (1997) Dis Colon Rectum, 40, pp. 317-321; Welsh, J., Induction of apoptosis in breast cancer cells in response to vitamin D and antiestrogens (1994) Biochem Cell Biol, 72, pp. 537-545; Chouvet, C., Vicard, E., Devonec, M., Saez, S., 1,25-Dihydroxyvitamin D3 inhibitory effect on the growth of two human breast cancer cell lines (MCF-7, BT-20) (1986) J Steroid Biochem Molecular Biol, 24, pp. 373-376; Hughes, P.J., Steinmeyer, A., Chandraratna, R., Brown, G., 1α,25-dihydroxyvitamin D stimulates steroid sulphatase activity in HL60 and NB4 acute myeloid leukaemia cell lines by different receptor-mediated mechanisms (2005) J Cell Biochem, 94, pp. 1175-1189; Finlay, I.G., Stewart, G.J., Shirley, P., Woolfe, S., Pourgholami, M.H., Morris, D.L., Hepatic arterial and intravenous administration of 1,25-dihydroxyvitamin D3 - evidence of a clinically significant hepatic first-pass effect (2001) Cancer Chemother Pharmacol, 48, pp. 209-214; Finlay, I.G., Stewart, G.J., Ahkter, J., Morris, D.L., A phase one study of the hepatic arterial administration of 1,25-dihydroxyvitamin D3 for liver cancers (2001) J Gastroenterol Hepatol, 16, pp. 333-337; Ariel, I.M., Treatment of inoperable primary pancreatic and liver cancer by the intra-arterial administration of radioactive isotopes (Y90 radiating spheres) (1965) Annual Surg, 162, pp. 267-278; Meade, V.M., Burton, M.A., Gray, B.N., Distribution of different sized microspheres in experimental hepatic tumours (1987) Eur J Cancer Clin On, 23, pp. 37-41; Sinha, V.R., Trehan, A., Biodegradable microspheres for protein delivery (2003) J Control Rel, 90, pp. 261-280; Gao, J., Qian, F., Szymanski-Exner, A., Stowe, N., Haaga, J., In vivo drug distribution dynamics in thermoablated and normal rabbit livers from biodegradable polymers (2002) J Biomed Mat Res, 62, pp. 308-314; Dowding, P.J., Vincent, B., Suspension polymerisation to form polymer beads (2000) Colloid Surface A, 161, pp. 259-269; Determan, A.S., Encapsulation, stabilization, and release of BSA-FITC from polyanhydride microspheres (2004) J Control Rel, 100, pp. 97-109; Mathiowitz, E., Langer, R., Polyanhydride microspheres as drug carriers: I. 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Keywords: 1,25 Dihydroxyvitamin D3, Liver cancer, Microspheres, Suspension polymerization, Biodegradability, Cytotoxicity, Oncology, Polymerization, Synthesis (chemical), Vitamins, Hepatocellular carcinoma, Hypercalcaemia, Drug delivery
DOI: 10.1016/j.eurpolymj.2007.02.019
ISSN: 00143057
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > Institutes > Institute for Future Environments
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 22 Sep 2016 04:50
Last Modified: 12 Oct 2016 04:38

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