Development of clinically effective formulations for anticancer applications: why it is so difficult?

Abstract To try and help answer the question, why is the “development of clinically effective formulations is so difficult?” especially for anticancer applications, this chapter is divided into two main parts. Part A deals with a series of nonscientific factors including drugs that are approved; the regulated process costs money to cross “the valley of death”; and just because it is approved does not mean it works, including two examples of billion-dollar drugs, Doxil and Abraxane. These are not significantly clinically effective compared to the free doxorubicin or existing formulations, cremophor EL and docetaxel. Part B has a more educational focus and is especially written for the students and postdocs doing the work. It reviews the science of designing, making, and testing nanomedicine formulations. I give two examples from the literature, a peptide–polymer–niclosamide formulation and an albumin–paclitaxel formulation, for us to consider quantitatively if they are likely to be clinically effective as they perhaps move forward into preclinical and human trials. My main message though is in two examples that we have developed or are developing. It is here that I explore the fundamental physicochemical and material properties of the drug itself are what make the formulation effective in combination with the right encapsulating material. These are our low temperature-thermal–sensitive liposome (LTSL) for treating local disease; and a new endogenously inspired nanoparticle, the niclosamide stearate prodrug therapeutic (NSPT), that “makes the drug look like the cancer’s food.” The chapter concludes with a perhaps unconventional notion that we might just be able to bring a clinically effective formulation to the clinic via a non-or-limited profit entity, with open-source pharmaceuticals, starting generic.