Nanoparticle researchers are developing a microfluidic platform for improved delivery of gene therapy for lung diseases

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Credit: ACS Nano (2024). DOI: 10.1021/acsnano.4c00768

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Credit: ACS Nano (2024). DOI: 10.1021/acsnano.4c00768

Drug delivery researchers at Oregon State University have developed a device with the potential to improve gene therapy for patients with inherited lung diseases such as cystic fibrosis.

In cell culture and mouse models, OSU College of Pharmacy scientists demonstrated a new technique for aerosolizing inhalable nanoparticles that could be used to deliver messenger RNA, the technology underlying COVID-19 vaccines, to patients’ lungs .

The findings are important because the current nebulization method for nanoparticles subjects them to shear stress, hindering their ability to encapsulate the genetic material and causing them to aggregate in certain parts of the lungs instead of spreading evenly, according to the researchers.

The study led by Gaurav Sahay, professor of pharmaceutical sciences, was published in ACS Nano.

Sahay’s lab studies lipid nanoparticles, or LNPs, as a gene delivery vehicle with a focus on cystic fibrosis, a progressive genetic disorder that results in persistent lung infection and affects 30,000 people in the U.S., with approximately 1,000 new cases identified annually.

One faulty gene – the cystic fibrosis transmembrane conductance regulator, or CFTR – causes the disease, which is characterized by drying of the lungs and a buildup of mucus that blocks the airways.

Lipids are organic compounds containing fatty tails and are found in many natural oils and waxes, and nanoparticles are small pieces of material ranging in size from one to 100 billionths of a meter. Messenger RNA provides instructions to cells for making a specific protein.

In the coronavirus vaccines, the mRNA carried by the lipid nanoparticles instructs the cells to make a harmless piece of the virus’ spike protein, triggering an immune response from the body. As a therapy for cystic fibrosis, the genetic material would repair the error in patients’ CFTR gene.

“We used a novel microfluidic chip that helps generate plumes carrying nanoparticles and does not cause shear stress,” Sahay said. “This device is based on the similar idea of ​​an inkjet cartridge that generates plumes to print words on paper.”

Four years ago, Sahay said, an Oregon-based startup called Rare Air Health Inc. contact him about the prospect of using microfluidic technology for the aerosolization and delivery of lipid nanoparticles.

Microfluidics is the study of how fluids behave as they travel through or are confined within microminiaturized devices equipped with channels and chambers. Surface forces dominate fluids on the microscale, unlike volumetric forces, meaning that fluids there behave much differently than what is observed in everyday life.

“When Rare Air came to me, I thought the device could work great for our purposes, and what followed were extensive studies demonstrating the superiority of this device in generating aerosolized nanoparticles compared to clinically used vibrating mesh nebulizers, Sahay said.

“The device does not allow the nanoparticles to aggregate and can deliver mRNA with higher precision than existing technology. The cool thing is that this device can be controlled digitally, and Rare Air is developing prototypes for human use.”

In addition to Sahay, the other Oregon State researchers who participated in the study were Yulia Eygeris, Jeonghwan Kim, Antony Jozić and Elissa Bloom. Scientists from Funai Microfluidic Systems of Lexington, Kentucky, were also part of the collaboration.

“Funai is focused on inkjet technology and building these chips at scale; they have worked closely together to make the device suitable for aerosolization,” said Sahay, who serves as an advisor and consultant for Rare Air in addition to his role at OSU. “This study demonstrates a marriage between new devices and formulation science that could have a dramatic impact on human health.”

More information:
Jeonghwan Kim et al., Microfluidic platform enables shearless aerosolization of lipid nanoparticles for mRNA inhalation, ACS Nano (2024). DOI: 10.1021/acsnano.4c00768

Magazine information:
ACS Nano