Simple tag puts IV chemotherapy drugs in pill form

Good news! Seems to be a very clever solution! Cancer is history (soon)!

"... Now, Stanford scientists have found “an embarrassingly simple solution” that could make almost any drug molecule effective in oral pill form, testing it in mice with chemotherapy drugs that are normally administered through IV infusion.

In essence, what the team has developed is a small molecular tag that can be attached to most drug molecules that makes them more effective as oral pills. ...

The problem with many oral drugs is bioavailability – how much of the dose is available for the body to absorb. Ideally, drugs need to be both water-soluble, to dissolve in the stomach and pass into the bloodstream, and oil-soluble to get into the cells to do their work. Doing both is tricky, so many drugs skip the water problem and focus on oil solubility, requiring IV infusion instead.

But the new tag is cleverly designed to change the solubility of the drug molecule it’s attached to. It starts off water soluble, but as the drug passes through the stomach or intestinal wall, enzymes there snip off the tag. As such, by the time the drug reaches the bloodstream it’s become oil soluble instead, ready to get to work. ..."

From the abstract:

"Though conceptually attractive, the use of water-soluble prodrug technology to enhance oral bioavailability of highly insoluble small molecule therapeutics has not been widely adopted. In large part, this is due to the rapid enzymatic or chemical hydrolysis of prodrugs within the gastrointestinal tract, resulting in drug precipitation and no overall improvement in oral bioavailability relative to standard formulation strategies. We reasoned that an optimal water-soluble prodrug could be attained if the rate of prodrug hydrolysis were reduced to favor drug absorption rather than drug precipitation. In doing so, the rate of hydrolysis provides a pharmacokinetic control point for drug delivery. Herein, we report the discovery of a water-soluble promoiety (Sol-moiety) technology to optimize the oral bioavailability of highly insoluble small molecule therapeutics, possessing various functional groups, without the need for sophisticated, often toxic, lipid or organic solvent-based formulations. The power of the technology is demonstrated with marked pharmacokinetic improvement of the commercial drugs enzalutamide, vemurafenib, and paclitaxel. This led to a successful efficacy study of a water-soluble orally administered prodrug of paclitaxel in a mouse pancreatic tumor model."

"Embarrassingly simple" tag puts IV chemotherapy drugs in pill form

New strategy could turn IV medicines into pills (original news release) "The method, which involves adding a small chemical tag onto existing drugs, could make it possible for chemotherapy patients to take pills rather than receive IV infusions."

Sol-moiety: Discovery of a water-soluble prodrug technology for enhanced oral bioavailability of insoluble therapeutics (open access)

Fig. 2: Schematic of the Sol-moiety concept.