Medical Device Daily National editor

Drug companies focused on the broad potential of personalized medicine, such as the customization of drug protocols to particular patients – vs. the pop-a-pill, take-a-cpasule, one-size-fit-all-approach – should probably pay close attention to some of the basic research work being done at the Massachusetts Institute of Technology (MIT; Cambridge, Massachusetts).

There, researchers are using a range of device and chemical/bio-engineering modalities to manipulate what can be done with drugs, vaccines, imaging agents and genetic and tissue materials.

And Kimberly Hamad-Schiefferli, PhD, assistant professor of biological and mechanical engineering at MIT, notes that the ability to use and manipulate more than one drug needs to be added to this personalized approach for some diseases.

"With a lot of diseases, especially cancer and AIDS, you get a synergistic effect with more than one drug," she told Medical Device Daily.

Thus, she is heading up research that has focused on this approach, not only for a combination of two drugs, but, potentially, more than two – and at different rates of dosing and elution.

Using tiny gold particles and infrared light, Hamad-Schiefferli and colleagues have developed a drug-delivery system that will enable multiple drugs to be released in a controlled fashion. This would provide the control needed when battling diseases commonly treated with more than one drug, according to the researchers.

This work, by Hamad-Schiefferli and colleagues, appears in a recent issue of the journal ACS Nano.

The paper describes how up to four different-shaped particles could be developed, each releasing its payload at different wavelengths when struck with infrared light.

Still only a "2," on the way to the full clinical development in the "10" range, the work, Hamad-Schiefferli says, was done in vitro, "in solution," and the next step will be proof of concept in cells.

But she also noted that the necessary related infrastructure, the lasers deliver" delivery devices" are in common use and available for the work – though in future clinical use they would have to be shrunk to handheld size.

She said that delivery devices already exist that enable the release of two drugs, "but the timing of the release must be built into the device – it cannot be controlled from outside the body."

The system that she and her colleagues have developed "is controlled externally and theoretically could deliver up to three or four drugs."

Explaining the method of action, she said that the infrared light is able to melt the gold nanoparticles, in the process releasing the drug payloads attached to them.

These particles, also called "nanorods," can be tuned" by changing their shapes and matching them to the different wavelengths of light and their ability to release the drugs, said Andy Wijaya, graduate student in chemical engineering and lead author of the paper.

The researchers built the nanoparticles in two different shapes, one they call "nanobones," the other, "nanocapsules," terms that simply reflect their shapes, according to Hamad-Schiefferli.

Nanobones melt at light wavelengths of 1,100 nanometers, and nanocapsules at 800 nanometers.

In the study, the researchers tested the particles, not with drugs, but rather with a payload of DNA. Each nanoparticle can carry hundreds of strands of DNA, and so the researchers said they could also be engineered to transport other types of drugs.

In theory, up to four different-shaped particles could be developed, each releasing its payload at different wavelengths.

This ability, Hamad-Schiefferli said, contrasts greatly with the usual delivery of drug, which she characterized as largely uncontrolled.

She says most drugs usually present to the body by "coming at once, with burst speed - they release once and then they're done."

In comparison, the nano-particle/infrared light combination will enable not only multiple-drug delivery but delivery of different amounts at different rates.

This, she said, will fit what is needed in the use of multiple therapies for some diseases, in which you may want a quick-burst initial delivery of one drug, followed by delivery of others, at different dosages and at longer terms.

In another version of their drug delivery work, the researchers are studying the ability to heat magnetic nanoparticles with an external field to achieve this in thermo-sensitive liposomes, found to be a vehicle for drug delivery.

Liposomes have a large internal aqueous space which can carry a payload. Upon heating these liposomes release their contents, so encapsulation of magnetic nanoparticles along with the drug of interest could enable externally triggered release.

Hamad-Schiefferli said, "We are studying how to encapsulate water soluble magnetic nanoparticles in liposomes at very high densities using the reverse-evaporation [REV] method. We have found that increasing the concentration of nanoparticles in liposomes can perturb the lipid phase diagram, and thus synthesis of large unilamellar vesicles encapsulating nanoparticles requires optimization of liposome synthesis parameters.

"We are developing a means of orthogonally heating nanoparticles, so that magnetic fields of one frequency could be used to heat one type of nanoparticle, and another frequency could be used to heat another independently.... by exploiting the size and material dependence of magnetic field heating."