Bizarrely shaped drug microparticles may change how you take medicine

Think of it as Amazon Prime for your immune system


There are few reminders of old age more regular that downing a colorful collection of pills and vitamins every morning.

In order to design next-generation drug delivery systems -- vitamins of the future -- scientists are looking to something very, very small.

This next-gen solution may come in the form of biocompatible microparticles that can be injected directly into one's bloodstream.

Previously, scientists had designed these super tiny drug curriers (think Amazon Prime but in your veins) using synthetic materials and precarious techniques that were either difficult to scale or not easily modified.

A new study from Duke University published this month in the journal Nature Communications is looking to change those precarious techniques by making use of "wet noodle"-like natural proteins that can be scaled down and modified using nothing more than light and heat.

Stefan Roberts, lead author on the study and biomedical engineering research scientist at Duke, said in a statement that this unique approach allowed them to create bizarre, never-before-seen microparticles for therapeutic use.

"We can make some pretty bizarre microparticles"

"With nothing more than some heat and light, we can make some pretty bizarre microparticles," said Roberts. "The technique is simple enough that it could be scaled up to make billions of microparticles in a matter of minutes."

The team was able to achieve this by looking at two different classes of proteins, one called ELPs (elastin-like polypeptides) which have a very disordered structure like the aforementioned wet noodles, and a slightly more organized class or proteins called POPs (partially ordered proteins) which are similar biological properties to ELPs but with slightly more structure. By combining these two different classes of proteins together, the team was able to explore how heat and light might change these proteins' structures.

"This is a test case for a type of material that is flexible and simple enough to create both commonly used shapes and architectures that aren't seen using current techniques," said Roberts. "We're using new biocompatible materials to create never-before-seen shapes simply by heating, cooling and shining a light on them."

A single POP microparticle seen up close and personal under a microscope.Stefan Roberts, Duke University

Through a series of experiments the research team was able to explore how changing the heat applied to these molecules could have them change shape, including to form shells with a solid core, shells with no core and tangle of shells on a cord that the team dubbed "fruits-on-a-vine." These molecules could then be frozen in a given shape once exposed to a flash of light.

Ashutosh Chilkoti, the Alan L. Kaganov Distinguished Professor of Biomedical Engineering at Duke, tells Inverse that this allows the molecules to keep their unassuming, blob-like outward shape while containing inside a multitude different pathways and shapes. Think about how the TARDIS is really larger than just a typical police box.

"These particles have extremely high surface area to volume ratios," says Chilkoti.

The researchers say that millions of particles like these can be created in only a few minutes and within the volume of liquid the size of a water droplet.

Thanks to their porous structure, Chilkoti says that these molecules could be used to diffuse drugs into patients or to craft stem cell growth for tissue engineering. But, exactly how these little molecules will be used in practice is still be determined.

"This is an enabling technology," Chilkoti tells Inverse. "Where it will become useful we don't know yet. Often you create new tools, you put them out and you don't know how the tool will get used because in a sense we rely on the creativity of others... We have some ideas on how to use it, but it's tough to say how the community might adopt it."

But Chilkoti says going forward he hopes to focus the team's research on exploring more of these real-world applications.

Abstract: The controllable production of microparticles with complex geometries is useful for a variety of applications in materials science and bioengineering. The formation of intricate microarchitectures typically requires sophisticated fabrication techniques such as flow lithography or multiple-emulsion microfluidics. By harnessing the molecular interactions of a set of artificial intrinsically disordered proteins (IDPs), we have created complex microparticle geometries, including porous particles, core-shell and hollow shell structures, and a unique ‘fruits-on-a-vine’ arrangement, by exploiting the metastable region of the phase diagram of thermally responsive IDPs within microdroplets. Through multi-site unnatural amino acid (UAA) incorporation, these protein microparticles can also be photo-crosslinked and stably extracted to an all-aqueous environment. This work expands the functional utility of artificial IDPs as well as the available microarchitectures of this class of biocompatible IDPs, with potential applications in drug delivery and tissue engineering.
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