Stanford Engineering researchers have created a new drug delivery platform that could allow patients with certain cancers, autoimmune diseases, and metabolic disorders to receive protein-based treatments through simple injections rather than lengthy intravenous (IV) infusions. The research was published on August 20 in Science Translational Medicine.
Currently, many protein therapeutics require high doses and are formulated at low concentrations for stability, making IV infusion the standard method of administration. The new formulation developed at Stanford enables these drugs to be stored and delivered at much higher concentrations, allowing for injection via a standard syringe or autoinjector device.
“This is a platform that potentially works with any biologic drug, so that we can inject it easily,” said Eric Appel, associate professor of materials science and engineering and senior author on the paper. “That takes these treatments from a several-hour ordeal at a clinic with an IV infusion to something you can do in seconds with an autoinjector at your house.”
A challenge with high-concentration protein therapeutics is their tendency to stick together, which increases viscosity and risks forming aggregates that may trigger immune responses or reduce effectiveness. To address this, the Stanford team developed a polyacrylamide copolymer called MoNi. MoNi has a high glass transition temperature, remaining solid at warmer temperatures where other additives would soften. By mixing MoNi into water with the protein drug and using spray drying—a common pharmaceutical process—they produced tiny particles of protein coated in MoNi.
“We ended up with something that looks like a candy-coated chocolate, where the protein is on the inside and our special polymer forms a solid, glassy coating on the outside,” Appel explained.
The powder was then suspended in liquid without dissolving it. The MoNi coating kept particles from sticking together and preserved proteins in a dry state until injection.
“Because the microparticles are spherical and have smooth surfaces, they’re able to roll over each other and still be able to go through tiny needles and be injected into a person, but you can hit really, really, high concentrations,” said Carolyn Jons, doctoral student in Appel’s lab and co-first author on the paper.
Testing involved three proteins: albumin, human immunoglobulin, and a monoclonal antibody treatment for COVID-19. Concentrations exceeding 500 mg/mL were achieved—more than double typical liquid injections—while maintaining smooth injectability. These formulations also showed stability after multiple freeze-thaw cycles or storage at elevated temperatures.
“The mechanical properties of these dried particles matter a lot more than the chemical structure of the individual drug molecules, which means we can take almost any protein drug and formulate it this way,” said Alexander Prossnitz, postdoctoral researcher and co-first author on the paper. “It ends up being a really big improvement over existing technologies.”
Spray drying is already widely used in pharmaceuticals; preclinical models have shown no adverse effects from MoNi so far. The technology has been licensed to a local startup aiming to refine it for new drug products.
“There are a lot of molecules that are promising drugs, but that you cannot turn into a drug product because they’re just too unstable given the constraints of currently available technologies,” Appel noted. “This platform is really sophisticated in its ability to stabilize proteins and enable new drug products that would not normally be feasible, and which can be administered in a way that is much less burdensome.”
Researchers hope future protein-based treatments will become faster and easier for patients.
“We know patients are willing to do injections themselves, especially if it’s in a simple autoinjector,” Prossnitz said. “If we can take an antibody that used to require an IV and let people inject it at home, that’s a big improvement. It totally changes how patients are able to manage their own diseases.”
Appel holds courtesy appointments in bioengineering and pediatrics (endocrinology), is affiliated with several Stanford institutes including Bio-X and ChEM-H, as well as various health research initiatives across campus. Additional Stanford contributors include graduate students Noah Eckman, Changxin Dong, and Ashley Utz.
Funding came from organizations such as the Stanford Maternal & Child Health Research Institute—the National Science Foundation—and others supporting early-career faculty development.
