Uhrich, Kathryn

	Phone:	732-445-0361
	E-mail:
	FAX:	732-445-7036
	Lab:	732-445-5630 (WRL 371)
	Office:	Wright-Rieman Labs, Rm 311 (Busch) / 77 Hamilton St, Rm 208 (CAC)
	Mail:	Chemistry & Chemical Biology, 610 Taylor Road, Piscataway, NJ 08854

Research Summary

The focus in the UGroup laboratory is the synthesis and characterization of biocompatible, biodegradable polymers for medical, dental, cosmetic and personal care applications.  We engage motivated and creative researchers from chemistry, engineering, biology and pharmacy at all levels - from high school students to visiting scientists from internatioanl labs.  This diverse and creative research environment leads to many discoveries; we learn the vocabulary of intellectual property (eg, patents) and industrial collaborations as it pertains to our published research in drug delivery.

Amphiphilc Macromolecules

Amphiphilic macromolecules (AMs) are essentially polymeric micelles that were first designed as nanocarriers to water-solubilize hydrophobic drug molecules.  Yet, in the past few years, we've discovered that the AMs themselves are bioactive and are valuable additives for lipid-based delivery systems.

Regarding bioactivity, the AMs specifically inhibit the uptake of "bad cholesterol" (ie, low density lipoproteins).  In collaboration with Prabhas Moghe (Rutgers, Biomedical Engineering), we examine methods to enhance biological interactions - evaluating amphiphilicity, branching, stereochemistry, pKa and other factors via new chemical structures.  With funding from NIH and the Coulter Foundation, we are developing novel polymers that may be used to treat cardiovascular disease.

With their ability to quickly migrate into the nucleus, we continue to optimize the AMs for delivery of genes (ie, siRNA) and anticancer agents.  In one approach with Charlie Roth (Rutgers, Biomedical Engineering), we include cationic elements - namely ethyleneimine - within the AM structure to promote siRNA complexation.  In another approach with Evan Mintzer (Stern College, Chemistry), we embed AMs with lipids to create AM-lipid complexes to promote delivery of water-insoluble drugs as well as siRNA.

Another critical aspect in developing novel technologies is stability - stability upon storage/sterilization and stability in vivo.  With J&J's Sterile Process Technology group, we demonstrate that the AMs remain unchanged with exposure to sterilization processes for J&J's products.  With Bob Prud'homme (Princeton, Chemical Engineering), the AMs are kinetically entrapped into nanoparticles via flash preciptiation such that AMs are delivered over extended time periods.

PolymerDrugs

PolyAspirin is the first example of a PolymerDrug: a polymer that degrades into a bioactive such as salicylic acid that can locally reduce inflammation and pain.  In addition to non-steroidal anti-inflammatory drugs (NSAIDs), several other drug classes are being investigated, including antiseptics, antioxidants, antimicrobials, and opiates.

By chemically incorporating morphine into a polymer (ie, PolyMorphine), we created a new composition that may alleviate tolerance development of opiates.  In our collaboration with Lei Yu (Rutgers, Genetics), we invented a polymer that extends pain relief from hours (as with injectable morphine) to days.

Localized delivery of salicylic acid is important for bone regeneration.  In our collaboration with Pat O'Connor (UMDNJ, Orthopedics), PolyAspirin suppresses inflammation, enabling bone formation.  With NIH funding, we are also investigating PolyAspirin formulations that can be syring-extruded to fill bone void volumes.

In a related project, we explore novel hydrogels that incorporate NSAIDs and/or antioxidants for wound care and personal care.  With Luiz Catalani (Univ Sao Paulo, Chemistry), stable hydrogels are fabricated by admixing NSAIDS that release over days (rather than hours).

Overall, PolymerDrugs can be designed to release drugs/bioactives from hours to days to weeks to months.  The release profile is "tuned" using various approaches - admixing small molecules into the polymer matrix, modifying the polymer's chemical structure and/or changing the matrix format (microspheres vs. slab vs. hydrogel).  POLYMERx is developing this technology to coat medical devices.

Awards & Honors (selected)

• Sioux Award, University of North Dakota, 2012
• Turner Alfrey Visiting Professorship, Michigan Macromolecular Institute, 2012
• POLY Fellow, American Chemical Society, 2012
• Finalist, Blavatnik Awards for Young Scientists, New York Academy of Sciences, 2007
• Buck-Whitney Award, American Chemical Society, 2005
• Thomas Alva Edison Patent Award: Medical/Technology Transfer - New Jersey R&D Council, 2003
• Fellow, American Institute for Medical and Biological Engineering, 2003

Recent Publications

Gu, L; Zablocki, K; Lavelle, L; Bodnar, S; Halperin, F; Harper, I; Moghe, P; Uhrich, KE “Impact of ionizing radiation on physicochemical and biological properties of an amphiphilic macromolecule”, Polymer Degradation and Stability, 97 1686-1689 (2012).

York, AW; Zablocki, KR; Lewis, DR; Gu, L; Uhrich, KE; Prud’homme, RK; Moghe, PV “Kinetically Assembled Nanoparticles of Bioactive Macromolecules Exhibit Enhanced Stability and Cell-Targeted Biological Efficacy”, Adv Mater, 24 (6) 733-739 (2012).

Sparks, SM; Waite, CL; Harmon, AH, Nusblat, NM Roth, CM; and Uhrich, KE “Efficient Intracellular siRNA Delivery by Ethyleneimine-modified Amphiphilic Macromolecules”, Macromol Biosci, 11 (9) 1192-1200 (2011).

Iverson, NM; Plourde, NM; Sparks, SM; Wang, J; Patel, E; Shah, P; Lewis, DR; Zablocki, K; Nackman, GB; Uhrich, KE; Moghe, PV “Dual Use of Amphiphilic Macromolecules as Cholesterol Efflux Triggers and Inhibition of Macrophage Athero-inflammation”, Biomaterials, 32 (32) 8319-8327 (2011).

Rosario-Melendez, R; Lavelle, L; Griffin, J; Bodnar, S; Halperin, F; Harper, I; Uhrich, KE “Stability of salicylate-based poly(anhydride-ester) to electron beam and gamma radiation”, Polym Deg and Stability, 96, 1625-1630 (2011).

Harmon, AM; Lash, MH; Sparks, SM; Uhrich, KE “Preferential Cellular Uptake of Amphiphilic Macromolecule-Lipid Complexes with Enhanced Stability and Biocompatibility”, J Control Rel, 153 (3) 233-239 (2011).

Harmon, AM; Lash, MH; Tishbi, N; Lent, D; Mintzer, EA; Uhrich, KE “Thermodynamic and Physical Interactions between Novel Polymeric Surfactants and Lipids: Towards Designing Stable, Polymer-Lipid Complexes”, Langmuir, 27 (15) 9131-9138 (2011).

Griffin, J; Delgado-Rivera, R; Meiners, S; Uhrich, KE “Salicylic acid-derived poly(anhydride-ester) electrospun fibers designed for regenerating the peripheral nervous system”, J Biomed Mater Res: Part A, 97 (3) 230-242 (2011).

Delgado-Rivera, R; Griffin, J; Ricupero, C; Grumet, M; Meiners, S; Uhrich, KE “Microscale Plasma-initiated Patterning of Electrospun Polymer Scaffolds” Coll Surf B: Biointerfaces, 84, 591-596 (2011).

Recent Patents