Single cell model for simultaneous drug delivery and efflux

Multidrug resistance (MDR) of some cancer cells is a major challenge for ch emotherapy of systemic cancers to overcome. To experimentally uncover the c ellular mechanisms leading to MDR, it is necessary to quantitatively assess both drug influx into, and efflux from, the cells exposed to drug treatmen t. By using a novel molecular microdelivery system to enforce continuous an d adjustable drug influx into single cells by controlled diffusion through a gel plug in a micropipet tip, drug resistance studies can now be performe d on the single cell level. Our dynamic model of this scheme incorporates d rug delivery, diffusive mixing, and accumulation inside the cytoplasm, and efflux by both passive and active membrane transport. Model simulations usi ng available experimental information on these processes can assist in the design of MDR related experiments on single cancer cells which are expected to lead to a quantitative evaluation of mechanisms. Simulations indicate t hat drug resistance of a cancer eel can be quantified better by its dynamic response than by steady-state analysis. (C) 1999 Biomedical Engineering So ciety. [S0090-6964(99)01502-7].