Highly loaded (Depot) Microparticle Delivery System for the Controlled Release of Aqueous Soluble Biologics and Therapeutics

Web Published:

Princeton Docket # 16-3225-1

Researchers in the Department of Chemical and Biological Engineering at Princeton University have developed a new method for synthesizing nanoparticles or microparticles comprised of aggregated nanoparticles having a hydrophilic core and a less polar shell.


Biologically derived therapeutics, or biologics, are the most rapidly growing segment of the pharmaceutical marketplace. However, there are still unmet needs in improving the delivery of biologics. Injectable polymeric nanoparticles and microparticles capable of releasing proteins and peptides over time periods as long as weeks or months have been a major focus in the effort to decrease the frequency of administration. Current processes for making microparticles are commonly based on water-in-oil-in-water (w/o/w) emulsification processes. The lack of control in the emulsion step and generally less than 10% loading have prevented commercial adoption of the process.


The invention of this microparticle process overcomes limitations of current processes for making microparticle delivery systems for soluble drugs and biologics. It uses an "inverse" precipitation route to precipitate aqueous soluble species with copolymers as nanoparticles having a hydrophilic, polar core and a less polar shell. Encapsulation of hydrophilic compounds at 50-90% loading, and with encapsulation efficiencies of 90+ % are achieved. The aggregation of these nanoparticles to form larger microparticles and monoliths provides a highly loaded construct (a depot) for the sustained and controlled release of actives. The scalability of the process is a major feature. This methodology uses Flash Nanoprecipitation (FNP).  FNP is currently a Princeton patented technology to prepare nanoparticle composites with amphiphilic copolymers.  FNP is effective in encapsulating active ingredients at high particle loadings which has not been achieved by other processes.



•       Controlled release of biologics or therapeutics

•       Synthesis of nanoparticles or microparticles with hydrophilic (aqueous soluble) cores



•       High loading (>50%)

•       Fast, controlled precipitation

•       Loading efficiencies (>90%)

•       Controlled release

•       Reproducible, scalable synthesis parameters and product design



Pagels, R.F., Prud’homme, R.K., “Polymeric nanoparticles and microparticles for the delivery of peptides, biologics, and soluble therapeutics.” Journal of Controlled Release, Volume 219, 10 December 2015, Pages 519-535.




Robert K. Prud’homme is a Professor of Chemical and Biological Engineering and the Director of the Program in Engineering Biology at Princeton University. His research focuses on how weak forces at the molecular level determine macroscopic properties at larger length scales. Equal time is spent understanding the details of molecular-level interactions using NMR, neutron scattering, x-ray scattering, or electron microscopy and making measurements of bulk properties such as rheology, diffusion of proteins in gels, drop sizes of sprays, or pressure drop measurements in porous media. A major focus of his lab’s research is on using self-assembly to construct nanoparticles for drug delivery and imaging. His work is highly interdisciplinary; many of the projects involve joint advisors and collaborations with researchers at NIH, Argonne National Labs, CNRS in France, or major corporate research.


Robert F. Pagels is a Ph.D. candidate at Princeton University and a National Science Foundation Graduate Research Fellow. He obtained his bachelor’s degree from the University of Delaware in chemical engineering. Upon graduation he received the Taylor Award and was named the outstanding male of the 2012 graduating class. His current research revolves around drug delivery and protein-nanoparticle constructs.


Chester Markwalter is a PhD. Student at Princeton University. He obtained his bachelor’s degree in Chemical Engineering from the University of Delaware and has previously worked as an associate research scientist at Bristol Myers Squibb for 3.5 years.


Intellectual Property & Development Status

Proof of concept studies have been completed and are available under confidentiality.

Patent protection is pending. The synthesis of nanocarriers uses Flash Nano Precipitation (FNP), has been successfully patented (US 8137699) and continuation applications are pending.

Princeton is seeking to identify appropriate partners for the further development and commercialization of this technology.



Laurie Tzodikov

Princeton University Office of Technology Licensing

• (609) 258-7256• tzodikov@princeton.edu

Xin (Shane) Peng

Princeton University Office of Technology Licensing

• (609) 258-5579• xinp@princeton.edu


Patent Information:
For Information, Contact:
Tony Williams
Associate Director
Princeton University
Robert Pagels
Robert Prud'homme
Chester Markwalter
drug delivery