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Synthesis and in vitro cytotoxic activity on human anaplastic thyroid cancer cells of lipoamino acid conjugates of gemcitabine
Author(s) -
Pignatello Rosario,
Vicari Luisa,
Pistarà Venerando,
Musumeci Teresa,
Gulisano Massimo,
Puglisi Giovanni
Publication year - 2010
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20374
Subject(s) - chemistry , nanocarriers , prodrug , liposome , in vitro , pharmacology , amphiphile , drug , biological activity , carbodiimide , conjugate , cytotoxicity , biochemistry , combinatorial chemistry , drug delivery , organic chemistry , medicine , mathematical analysis , mathematics , copolymer , polymer
Abstract Lipophilic derivatives of the antitumor drug gemcitabine (GEM) with the potential for improving drug loading in lipid‐based colloidal carriers, like liposomes or lipid nanoparticles, are described. GEM free base was conjugated to lipoamino acids bearing an alkyl side chain of different length, by either a carbodiimide‐assisted or an ethylchloroformiate‐assisted coupling reaction, to obtain N 4 ‐acyl GEM derivatives. These compounds retained the same in vitro cell growth inhibitory activity of the parent drug against two lines of human anaplastic thyroid cancer cells. Stability studies suggested that the observed activity was due mainly to intact derivatives and not to released GEM. Accordingly, these amphiphilic derivatives can be proposed in a further step for the encapsulation in liposomes or lipid nanocarriers, to achieve as a final goal an improvement of the pharmacokinetics and therapeutic activity of GEM. Drug Dev Res 2010. © 2010 Wiley‐Liss, Inc.