Anticancer conjugates of 5-fluorouracil (5-Fu) and polyaspartamide, containing pyridoxamine as the hepatocyte-targeting group, were synthesized and characterized. Their sustained release properties and biodistribution were evaluated. The 5-Fu was targeted to specific organs, such as the liver, and had a sustained in vitro release rate in PBS. In vitro cytotoxicity assay showed that the polymeric drugs exhibited low cytotoxicity to the human liver cells (L-02). These polymeric drugs possess high anticancer efficiencies and induced apoptosis in the human hepatic tumor cells (Bel-7204).
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References
1.
1. R. Langer, Polymer-controlled drug delivery systems, Acc. Chem. Res.26 (1993) 537–542.
2.
2. M. Nishikawa and Y. Takakura, Pharmacokinetic evalution of polymeric carriers, Adv. Drug Del. Rev.21 (1996) 135–155.
3.
3. H. Sezaki, Y. Takakura and M. Hashida, Soluble macromolecular carriers for the delivery of antitumor drugs, Adv. Drug Del. Rev.3 (1989) 247–266.
4.
4. M. Yokoyama and S. Inoue, Preparation of adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer, Macromol. Chem., Rapid Commun.8 (1987) 431–435.
5.
5. E. Rummeny, C. Ehrenheim, H. B. Gehl, et al., Manganese-DPDP as a hepatobiliary contrast agent in the magnetic resonance imaging of liver tumors: results of clinical phase II trials in Germany including 141 patients, Invest. Radiol., 26 (1991) S124–125.
6.
6. B. E. V. Beers, B. Gallez and J. Pringot, Contrast-enhanced MR imaging of the liver, Radiology, 203 (1997) 297–306.
7.
7. S. M. Rocklage, W. P. Cacheris, S. C. Quay, et al., Manganese N, N′-dipyridoxyl ethylenediamine-N, N′-diactate-5, 5′-bis(phosphate): synthesis and characterization of a paramagnetic chelate for magnetic resonance imaging enhancement, Inorg. Chem.28 (1989) 477–485.
8.
8. S. M. Rocklage and S. C. Quay, Dipyridoxyl phosphate nuclear magnetic resonance imaging contrast agents. EP 290 047 (1988).
9.
9. J. F. Wei and R. X. Zhuo, Study on the novel magnetic resonance imaging contrast containing vitamin B6 as hepatocyte-targeting group, Chin. Sci. Bull.42 (1997) 1519–1524.
10.
10. G. Giammona, B. Carlisi and S. Palazzo, α, β-Poly(N-hydroxyethyl) DL-aspartamide with derivatives of carboxylic acids, J. Polym. Sci. Polym. Chem.25 (1987) 2813–2818.
11.
11. G. Giammona, B. Carlisi, G. Cavallaro, et al., Calorimetric investigation of the interaction between,α,β-Poly(N-hydroxyethyl)-DL-aspartamide and surfactants, Int. J. Pharm.64 (1990) 239–242.
12.
12. G. Giammona, B. Carlisi, G. Pitarresi, et al., Hydrophilic and hydropholic polymeric derivatives of antiinflammatory agents such as Alclofenac, Ketoprofen and Ibuprofen, J. Bioact. Compatible Polym.6(1991) 129–141.
13.
13. G. Giammona, B. Carlisi and G. Pitarresi, et al., Water-soluble copolymers of an antiviral agent: synthesis and their interaction with a biomembrane model, J. Control. Release22 (1992) 197–204.
14.
14. G. Giammona, G. Cavallaro and G. Fontana, et al., Coupling of the antiviral agent zidovudine to polyaspartamide and in vitro drug release studies, J. Control. Release54 (1998) 321–331.
15.
15. R. X. Zhuo, G. P. Yan and M. Y. Xu, Macromolecular MRI contrast agents containing hepatocyte-targeting group, 2000 Society for Biomaterials Sixth World Biomaterials Congress Transactions, Volume (III), pp 1447-1447 (May 15–20, 2000, Kamuela, Hawaii, U.S.A)
16.
16. R. X. Zhuo, Y. J. Fu and J. Liao, Synthesis, relaxivity and biodistribution of novel magnetic resonance imaging (MRI) contrast agents: polylysine (Gd-DTPA/DOTA) with pendant galactose moieties as hepatocyte-targeting groups, Chin. Chem. Lett.8 (1997) 157–160.
17.
17. W. D. Huang and C. Q. Chen, Synthesis of polypeptides, 1985, pp 14–15.
18.
18. E. M. Neuse, A. G. Perlwitz and S. Schmitt, Water-soluble polyamides as potential drug carriers, Macromol. 192 (1991) 35–50.
