Molecules’ movements through membrane present new puzzle

Discovery at Houston Methodist, Rice will impact design of drug delivery systems at the molecular level

A discovery by researchers at Houston Methodist Research Institute and Rice University could impact drug delivery systems, water filtration and energy production.

The team investigating how drug molecules in a solution travel through a nanofluidic membrane found that the molecules and membrane do not interact as expected.

The findings are described in Nature Communications.

Pimpinelli

Nanofluidic membranes act as filters that allow molecules to flow through hundreds of thousands of uniform nanoscale channels. The new membranes were created with semiconductor technology commonly used to fabricate computer microchips.

They were designed by Alessandro Grattoni, chairman of the Department of Nanomedicine at Houston Methodist; Mauro Ferrari, Methodist president and CEO; and colleagues. They were part of the research team, which also included Rice’s Alberto Pimpinelli, an adjunct lecturer in materials science and nanoengineering and executive director of the university’s Smalley-Curl Institute.

“Our lab develops implantable systems for controlled drug delivery to treat chronic diseases over extended periods of time,” said Grattoni, the lead author. “These implants use silicon nanofluidic membranes, each of which has a precise number of identical nanochannels.”

The implants require membranes that are mechanically robust, biochemically inert and have a high density of channels that allow drug delivery at clinical doses.

“We are interested in better understanding what happens inside these channels and in what way the drug travels across them,” Grattoni said. “Particularly, we are focusing on the physics that underlies the transport across these membranes. This insight could additionally be useful in the extraction of natural gas, renewable energy production and in fluid and water filtration.”

Dr. Alessandro Grattoni of Houston Methodist Research Hospital holds samples of the nanochannel devices used to test their capabilities as filters for controlled drug-delivery implants. The membranes act as filters with hundreds of thousands of uniform nanoscale channels. Photo courtesy of the Houston Methodist Research Institute

The membranes can be used for a wide variety of drugs by customizing the size of the channel. The team developed an algorithm to select a size — from 2.5 to 250 nanometers — for various drugs’ molecular weight and other properties. In these tiny spaces, drug molecules strongly interact with the charged channels, affecting their transport.

“My part was pushing the mathematical and theoretical description to its limits, so we could test whether what we were observing was something novel or not,” said Pimpinelli, an affiliate member at Methodist. “With these tools, we can work out theories that are superior to any in existence, because experiments can be done with such precision.”

The researchers observed that molecules with positive and negative charges behaved about as expected as they approached and passed through the channels. But neutral molecules, which they expected to be unaffected, behaved as though they were carrying a charge, a phenomenon they couldn’t explain with current molecular transport theories.

Additionally, for all the molecules – positive, negative and neutral – they observed a steep, abrupt decrease in transport rate and diffusivity across the membrane at the ultra-nanoscale, below a channel size of 5 nanometers.

“These results are interesting because they challenge our theoretical understanding of how the transport of simple molecules into a relatively simple but electrically charged environment works when the scale is on the order of a few nanometers,” Pimpinelli said. “Some new insight will definitely come out of this.”

Co-authors of the paper are Giacomo Bruno, Nicola Di Trani, R. Lyle Hood, Erika Zabre, Carly Sue Filgueira, Priya Jain, Zachary Smith and Sharath Hosali of Methodist, and Giancarlo Canavese and Danilo Demarchi of Polytechnic of Turin, Italy. Bruno and Di Trani also are affiliated with Polytechnic of Turin.

The Center for the Advancement of Science in Space, the National Institutes of Health’s National Institute of General Medical Sciences and the Nancy Owens Memorial Foundation supported the research.

Lisa Merkl, medical research editor at Houston Methodist Research Institute, contributed to this report.