Low-Cost Targeted Therapies: As Easy as Uncooking an Egg?

Colin Raston FRACI CChem FRSC

Colin Raston, FRACI, CChem, FRSC

A headline gaining international attention has announced that a machine, the vortex fluidic device (VFD), invented by Colin Raston,FRACI, CChem, FRSC, a South Australia Premier's Professorial Research Fellow in Clean Technology at Flinders University, can “uncook” an egg.^1-3Yes, it is capable of “uncooking” an egg, but the current excitement about the potential of this device is that the latest research demonstrates it can also manufacture new targeted cancer therapies, and at lower costs.^1-4

The VFD has a rapidly rotating tube, open at one end and, depending on the speed of rotation, orientation of the tube, and other parameters, applies very high sheer forces to thin films of liquids fed into the system. It can also function in continuous flow mode with jet feeds delivering liquid into the device.^1,2“It’s a stunningly simple approach to apply sheer forces to reorganize matter in a controlled way,” said Raston.²

The explanation for how it “uncooks” an egg³(the egg white in this case) hinges on the forces generated by the speed of rotation and tilt of the tube, untangling the intertwined proteins so they can reassemble back into their normal structures in solution. Its conception arose from previous ideas and work. “We had developed continuous flow spinning disc technology for a number of different processes, but it [the process] suffered from the high cost of construction of the device, high volumes of liquids even for research purposes, and very short processing times,” said Raston in an interview withTargeted Oncology. “The VFD is relatively low cost to construct, and processing volumes can be reduced down to submilliliter or scaled up to one liter per hour, and the processing times can be controlled. In addition, the device is portable — it fits in a suit case!”

Raston and colleagues discovered this technology increased the loading of second-generation anticancer carboplatin drugs into nanoparticles, 100 nanometers in diameter, from 17% to 75%. “We’ve shown in laboratory experiments that by having the drug in the nanoparticle multiplies its efficacy in killing cancer cells by around four to five times,” said Raston^2,4“This not only would have a direct benefit of reducing the negative side-effects, which affect patient health, but of being able to use less of the drug."²

Referring specifically to the carboplatin nanoparticles, “The vesicle was developed for the binding of carboplatin. The approach of using shear forces (mechanical forces) in the VFD can be used for vesicles based on other lipids, with different drug molecules, where the drug is confined within the core of the nanodelivery vehicle. This could also work for the present vesicle,” said Raston.

When appropriate, combination therapy is a widely used approach in oncology, and, Raston further elaborated on the potential of the current results, “The carboplatin is embedded within the bilayer of the artificial lipid, and the scene is set for incorporating other drugs in the core of the vesicle, with or without the relatively small carboplatin molecule embedded in the bilayer. It is possible to be able to load the vesicle with a combination of drugs, using the mechanical forces in the VFD.”

Raston summed up the potential of VFD technology in the development of new therapeutics in oncology as, “The ability to bind an anticancer drug in a vesicle with close to the optimum size of 100 nm for cancer therapy, with the surface of the vesicle sensitive to change in pH, having a high release rate of carboplatin at Ph 5.5 relative to normal physiological pH.”

As with all new promising technologies, the test will revolve around whether or not oncology treatment centers will be able to obtain and operate the VFD and use it to individualize treatments. On this issue Raston commented, “Given the portable nature of the device, and relatively low cost, this is a realistic goal.”

References

1. Yasmin L, Chen X, Stubbs KA, et al. Optimising a vortex fluidic device for controlling chemical reactivity and selectivity.Sci Rep. 2013;3:2282. doi: 10.1038/srep02282

2.http://theleadsouthaustralia.com.au/industries/health/machine-can-unboil-an-egg-and-make-targeted-cancer-drugs/. Accessed May 22, 2015.

3. Yuan TZ, Ormonde CF, Kudlacek ST, et al. Shear-stress-mediated refolding of proteins from aggregates and inclusion bodies.Chembiochem. 2015;16:393-396

4. Mo J, Eggers PK, Chen X,etal. Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy.Sci Rep. 2015 May 22;5:10414. doi:10.1038/srep10414.