Synthesis and in vitro antitumor effect of diclofenac and fenoprofen thiolated and nonthiolated polyaspartamide-drug conjugates.
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.
Barbarić
M
M
Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovacića 1, HR-10000 Zagreb, Croatia.
Kralj
M
M
Marjanović
M
M
Husnjak
I
I
Pavelić
K
K
Filipović-Grcić
J
J
Zorc
D
D
Zorc
B
B
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D045744:Cell Line, Tumor; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor; D005279:Fenoprofen / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D009757:Nylons / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D009757:Nylons; D011355:Prodrugs; D013438:Sulfhydryl Compounds; D004008:Diclofenac; D001224:Aspartic Acid; D005279:Fenoprofen