ABSTRACT
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.
Subject(s)
Antineoplastic Agents/chemical synthesis , Diclofenac/analogs & derivatives , Diclofenac/chemical synthesis , Fenoprofen/analogs & derivatives , Fenoprofen/chemical synthesis , Nylons/chemistry , Prodrugs/chemical synthesis , Sulfhydryl Compounds/chemistry , Antineoplastic Agents/pharmacology , Aspartic Acid/analogs & derivatives , Aspartic Acid/chemistry , Cell Line, Tumor , Diclofenac/pharmacology , Drug Carriers , Drug Screening Assays, Antitumor , Fenoprofen/pharmacology , Humans , Prodrugs/pharmacology , Structure-Activity RelationshipABSTRACT
Synthesis of poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)]-thioglycolic acid (PHEA-TGA) conjugate as a new polyaspartamide thiomer is described. The parent polymer PHEA is chemically modified by introducing sulphydryl-bearing compound thioglycolic acid. By varying the reaction conditions several batches of PHEA-TGA conjugates were prepared and analyzed. Tensile studies revealed that total work of adhesion of PHEA-TGA increased more than twice compared to the unmodified polymer. Microparticles prepared from the thiolated polymer preserved its bioadhesive properties.
