Barbarić M, Kralj M, Marjanović M, Husnjak I, Pavelić K, Filipović-Grcić J, Zorc D, Zorc B
Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovacića 1, HR-10000 Zagreb, Croatia.
Eur J Med Chem. 2007 Jan;42(1):20-9. doi: 10.1016/j.ejmech.2006.08.009. Epub 2006 Sep 27.
This paper reports the synthesis and antiproliferative effects of new thiomer-diclofenac and fenoprofen conjugates, hydrophilic, bioadhesive, polymeric prodrugs, as well as antiproliferative effects of diclofenac, fenoprofen and a series of previously described polymer-fenoprofen conjugates on five tumor cell lines. Thiolated and nonthiolated polyaspartamides were the chosen polymeric components. Drug-loading ranged from 5.6 to 22.4%, and the amount of SH groups ranged from 6.9 to 45.6micromol g(-1). Tensile studies demonstrated a clear correlation between the amount of thiol and the mucoadhesive properties of the conjugates. The growth-inhibitory activity of the tested polymer-drug conjugates demonstrates that polyaspartamide-type polymers, especially thiolated polymers, enable inhibition of tumor cell growth with significantly lower doses of the active substance.
