This sponsored article is brought to you by NYU Tandon School of Engineering.
In a major advance in the field of drug delivery, researchers have developed a new technology that addresses an ongoing challenge: the scalable manufacturing of nanoparticles and microparticles. This innovation is led by
Natalie M. PinkertonThe assistant professor of chemical and biomolecular engineering at New York University’s Tandon School of Engineering, promises to bridge the gap between laboratory-scale drug delivery research and large-scale drug manufacturing.
This breakthrough, known as sequential nanoprecipitation (SNaP), builds on existing nanoprecipitation techniques to provide improved control and scalability, which are key to ensuring that drug delivery technologies reach patients efficiently and effectively. This technology enables scientists to
Manufacturing drug-bearing molecules that maintain their structural and chemical integrity from laboratory settings to mass production– An essential step towards bringing new treatments to the market.
Using 3D printing to overcome the challenge in drug delivery
Nanoparticles and microparticles hold tremendous promise for targeted drug delivery, allowing precise delivery of drugs directly to disease sites while minimizing side effects. However, consistently producing these particles on a large scale has been a major obstacle to translating promising research into viable treatments. As Pinkerton explains, “One of the biggest barriers to translation of many of these precision medicines is manufacturing. With SNaP, we are tackling this challenge head-on.”
Pinkerton is an assistant professor of chemical and biomolecular engineering at NYU Tandon.NYU Tandon School of Engineering
Conventional methods such as flash nanoprecipitation (FNP) have been successful in creating some types of nanoparticles, but often struggle to produce larger particles, which are necessary for some delivery methods such as inhaled delivery. FNP creates core-shell polymeric nanoparticles (NPs) ranging in size from 50 to 400 nm. The process involves mixing drug molecules and copolymers (special molecules that help form molecules) in a solvent, which is then quickly mixed with water using special mixers. These mixers create small, controlled environments where particles can form quickly and evenly.
Despite its success, FNP has some limitations: it cannot create stable particles larger than 400 nanometers, the maximum drug content is about 70 percent, production is low, and it can only work with hydrophobic (water-repelling) molecules. These problems arise because particle core formation and particle stabilization occur simultaneously in the FNP. The new SNaP process overcomes these limitations by separating the basic configuration and installation steps.
In the SNaP process, there are two mixing steps. First, the basic ingredients are mixed with water to begin forming the particle core. A stabilizing agent is then added to stop the growth of the nucleus and stabilize the particles. This second step must be done quickly, less than a few milliseconds after the first step, to control particle size and prevent aggregation. Current SNaP setups connect two dedicated mixers in series, controlling the delay time between steps. However, these devices face challenges, including high costs and difficulties in achieving the short delay times needed for small particle formation.
A new approach using 3D printing has solved many of these challenges. Advances in 3D printing technology now allow the creation of the precise and narrow channels required for these mixers. The new design eliminates the need for external tubing between steps, allowing for shorter delay times and preventing leaks. The innovative blender design combines two blenders into one setting, making the process more efficient and easier to use.
“One of the biggest barriers to translation of many of these precision medicines is manufacturing. With SNaP, we are tackling this challenge head-on.”
—Natalie M. Pinkerton, NYU Tandon
Using this new design of the SNaP mixer, the researchers successfully created a wide range of nanoparticles and microparticles loaded with rubrene (a fluorescent dye) and cinnarizine (a weakly hydrophobic drug used to treat nausea and vomiting). This is the first time that small sub-200 nm nanoparticles and microparticles have been synthesized using SNaP. The new setup also demonstrated the critical importance of the delay time between the two mixing steps in controlling particle size. This control of the delay time allows researchers to access a greater range of particle sizes. In addition, successful encapsulation of both hydrophobic and hydrophobic drugs in nanoparticles and microparticles using SNaP has been achieved for the first time by the Pinkerton team.
Democratizing access to cutting-edge technologies
The SNaP process is not only innovative, but also provides a unique practical application that democratizes access to this technology. “We’re sharing the design of our blenders and proving that they can be manufactured using 3D printing,” says Pinkerton. “This approach allows academic laboratories and even small-scale industrial players to experiment with these technologies without investing in expensive equipment.”
Access to SNaP technology could accelerate progress in drug delivery, enabling more researchers and companies to use nanoparticles and microparticles in the development of new therapeutics.
The SNaP project represents a successful multidisciplinary effort. Pinkerton highlighted the diversity of the team, which includes experts in mechanical and process engineering in addition to chemical engineering. “It was truly an interdisciplinary project,” she noted, noting that the contributions of all team members — from undergraduate students to postdoctoral researchers — were instrumental in bringing the technology to life.
Beyond this accomplishment, Pinkerton envisions SNaP as part of its broader mission to develop global drug delivery systems, which could ultimately transform healthcare by allowing for diverse, scalable, and customizable drug delivery solutions.
From industry to academia: a passion for innovation
Before arriving at NYU Tandon, Pinkerton spent three years in Pfizer’s oncology research unit, where she developed new nanomedicines for the treatment of solid tumors. She says the experience was invaluable. “Working in the industry gives you a realistic perspective on what is possible,” she points out. “The goal is to conduct translational research, meaning it ‘translates’ from the laboratory bench to the patient’s bedside.”
Pinkerton — who earned a bachelor’s degree in chemical engineering from MIT (2008) and a doctorate in chemical and biological engineering from Princeton University — was drawn to NYU Tandon, in part because of the opportunity to collaborate with researchers around the world. NYU ecosystem, with which it hopes to develop new nanomaterials that can be used for controlled drug delivery and other biological applications.
She also came to academia because of a love of teaching. At Pfizer, she realized her desire to mentor students and pursue innovative, interdisciplinary research. “Students here want to become engineers; “They want to make a difference in the world,” she said.
Her team at Pinkerton Research Group focuses on developing responsive soft materials for critical applications ranging from controlled drug delivery to vaccines and medical imaging. Taking an interdisciplinary approach, they use tools from chemical engineering, materials engineering, nanotechnology, chemistry and biology to create soft materials via scalable synthetic processes. They focus on understanding how process parameters control the properties of the final material, and thus how matter behaves in biological systems – with the ultimate goal being to create a global drug delivery platform that improves health outcomes across diseases and disorders.
Its SNaP technology represents a promising new direction in the quest to effectively scale drug delivery solutions. By controlling assembly processes with millisecond precision, this method opens the door to the creation of increasingly complex molecular architectures, providing a scalable approach for future medical advances.
For the drug delivery space, the future is bright as SNaP paves the way towards an era of more intuitive, adaptable and scalable solutions.