Sustainable medication: Microtechnology for personalizing drug treatment

Medication is an essential and costly part of global public health care, and the price of pharmaceuticals has increased steadily over the past decades. Recent statistics indicate that expenses may be stabilizing due to an increased public focus on the non-­‐sustainable growth in total health care expenditure. Cost levels have stabilized by increasing competition between the pharmaceutical producers and through guidelines between hospitals on how to apply the most cost-­‐effective medication for given disease conditions. Personalized drug treatment extends the latter concept by testing the effectiveness of candidate drugs on the individual patient prior to treatment. Thus, only useful medication is prescribed implying fewer societal expenses and better patient health. A large and growing number of specific biomarkers are developed to stratify patients into drug responders or non-­‐responders based on one or more biochemical or genetic characteristics. However, stratification is typically a yes/no outcome that does not predict optimal drug dose or timing in the individual. Furthermore, existing biomarkers fair poorly in guiding patient treatment with combination drug regimens as commonly used, for example in cancer chemotherapy. In the Danish Strategic Research Project “IndiTreat -­‐ Individualized Treatment of colorectal cancer” we pursue a radically different approach by testing all approved drug combinations on each patient’s cells to predict the most optimal treatment. Massive drug testing calls for development of scalable nano-­‐ and microtechnologies suitable for culturing patient cells or cell clusters, and for easy and safe dosing of the patient cells with toxic drugs in normal hospital settings. Here, we will focus on easy scalable drug dosing of cells by introducing “digital drug dosing” using light-­‐polymerizable polymer hydrogels as carriers for free or nanoparticle-­‐encapsulated drugs. The total dose is simply controlled by the volume of drug-­‐loaded cross-­‐ linked hydrogel defined by patterned light from a standard projector (Fig. 1). The concept enables simple immobilization of multiple drugs and triggered release of drugs from embedded liposome nanoparticles