In vitro permeability studies of antitumor compounds, thioxanthones across two model barriers, and their availability in vivo
One of the reasons for poor response of tumors is their three dimensional structure (micro-environment), which forms a penetration barrier to anti-tumor agents. A drug has to cross the interstitial space of tumors and many layers of cells to reach the interior of a tumor. The main objective of this study was to develop two new in vitro models to evaluate the in vivo availability of antitumor compounds to solid tumors. Two in vitro models, basement membrane p:1atrix of Engelbreth-Holm Swarm (EHS) mouse sarcoma (Matrigel) and human colorectal adenocarcinoma (Caco-2) multilayers were developed. The permeability characteristics of SR271425 (N-[1-{ [2-(diethylamino) ethyl] amino} -7 -methoxy-9-oxo-9H -thioxanthen-4-yl] methylformamide) a novel antitumor compound and three of its thioxanthone analogs (probable metabolites) were studied to evaluate the in vitro models.
Antineoplastic agents, Tumors, Chemotherapy, Medicine and Health Sciences, Pharmacy and Pharmaceutical Sciences
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