Research

Dr. Mathiowitz has worked on developing novel bioadhesive delivery systems. These systems range from basic engineering of fundamental science to the measurement of tensile forces between tissue/materials interactions, to designing smart delivery systems including the bioadhesive novel polymers.

The overall aim was to develop an effective oral delivery system for peptide and proteins based on safe, biocompatible, biodegradable, nanoparticles.  Specifically developing engineered bioerodible nanoparticles that, once delivered to the mucosal tissue, are capable of penetrating the barrier, reach the epithelium, penetrate the cell and distribute to internal organs. This was achieved by developing an encapsulation technique, which first stabilizes sensitive proteins for delivery after oral delivery; the polymer then degrades thereby releasing the encapsulated protein. Additionally, nanoparticles were designed using a very specific bioadhesive coating that are capable of delivering the nanoparticles to intestinal tissue in order to enhance penetration and control the uptake. Recently, two major publication (PNAS, 2013 and JCR, 2013) from her lab demonstrated that the relatively high degree of microsphere uptake in the absorptive and non-absorptive epithelium indicates that endocytosis as well as phagocytotic mechanisms are responsible for MS uptake in the small intestine.

In addition, specific bioadhesive coatings can enhance particle uptake from 6% to 70%. The results of these studies provide strong support for the use of bioadhesive polymers to enhance nano- and microparticles uptake from the small intestine for oral drug delivery. This study, using nanoparticles as penetrating delivery systems demonstrated that the non-lymphoid tissue of the absorptive epithelium could absorb MS and facilitate their biodistribution throughout the rat. These findings may potentially guide research aimed at delivering specific molecules to target organs. In addition, the methods and in vivo model that was used may also be useful to toxicologists who are interested in determining the fate or tissue distribution of microparticles, including whether such particles can cross the blood-brain barrier.

In the area of microencapsulation, Dr. Mathiowitz’s work focuses on using basic concepts of polymer phase separation phenomenon to design self-assembled microspheres, vascular grafts and fiber reinforced by Solvent induced crystallization.  One example is the development of Multi-walled microsphere (Nature 1994); many approaches for controlled release of drugs involves incorporation of the drug molecules into the matrix of microscopic polymer spheres or capsules. Those existing methods for preparing such micro-particles do not, however, always guarantee a constant release rate.  For example, drug molecules may be trapped preferentially at the surface; they have to diffuse through an increasing thickness of polymer when the particles are non-eroding, or the surface area changes for eroding particles. In other situations, pulsed release may be required—an application to which simple polymer microspheres do not readily lend themselves. Dr. Mathiowitz’s work on how to engineer Multi-walled microspheres might solve some of these problems. She has developed a one-step process for preparing double-walled polymer microspheres based on phase separation between polymer mixtures, with an appropriate choice of interfacial tensions and evaporation rate, a spherical droplet of one polymer becomes coated with a highly uniform layer of the other.

Dr. Mathiowitz’s work resulted in major publications, but also translated into two start-up companies, Spherics, Inc. and Perosphere, Inc., which focus their efforts on developments to improve patient compliance.