Uhrich, Kathryn

Position: 
Professor

Kathryn Uhrich

Phone: 848-445-0361

E-mail: E-mail

FAX: 732-445-7036

Lab: 848-445-5630 (WRL 371)

Office: Wright Rieman Labs, Rm 311 (Busch)

Mail: Chemistry & Chemical Biology, 610 Taylor Road, Piscataway, NJ 08854

 

Education Links

Research Summary

The focus in the UGroup laboratory is the design of biocompatible, biodegradable polymers that will improve human health.  Given that our starting materials are derived from natural sources, we also consider green chemistry approaches to the polymer life-cycle.  We engage motivated and creative researchers from chemistry, engineering, biology and pharmacy at all levels - from high school students to visiting scientists from international 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.  We demonstrated that these systems enhance delivery of anticancer drugs and effectively deliver siRNA into cancer cells. The dramatic change was our observation that AMs control cellular uptale of LDL and inhibit athero-inflammation. We now design anti-atherogenic polymers that target macrophage receptors and mitigate LDL uptake.

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.

AM siRNAWith 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.

polymorphineBy 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 Dana Graves (UPenn, Periodontics), we've demonstrated significant bone regeneration in diabetic animals with PolyAspirin-containing bone allograft material.

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).  PRx is developing this technology to incorporate into medical devices.


Awards & Honors (selected)

  • Fellow of National Academy of Inventors, 2013
  • Common Pathways Award, NJ Association for Biomedical Research, 2013
  • Sioux Award, University of North Dakota, 2012
  • Turner Alfrey Visiting Professorship, Dow/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

Ouimet, MA; Stebbins, ND; Uhrich, KE “Biodegradable Coumaric Acid-based Poly(anhydride-ester) Synthesis and Subsequent Controlled Release”, Macromol Rapid Commun, 34 (15) 1231-1236 (2013).

Poree, DE; Zablocki, K; Faig, A; Moghe, PV; Uhrich, KE “Nanoscale Amphiphilic Macromolecules with Variable Lipophilicity and Stereochemistry Modulate Inhibition of Oxidized Low-Density Lipoprotein Uptake”, Biomacromolecules, 14 (8) 2463-2469 (2013).

Mitchell, A; Kim, B; Cottrell, J; Engler, S; Witek, L; Ricci, J; Uhrich, KE; O’Connor, JP, “Development of a Guided Bone Regeneration Device using Salicylic Acid-Poly(anhdyrides-ester) Polymer and Osteoconductive Scaffolds”, J Biomed Mater Res: Part A (2013); published online: 18 May 2013.

Lewis, DR; Kholokovych, V; Tomasini, MD; Abhelhamid, D; Petersen, LK; Welsh, WJ; Uhrich, KE; Moghe, PV “In Silico Design of Anti-Atherogenic Biomaterials” Biomaterials 34 (32) 7950-7959 (2013).

Wada, K; Yu, W; Elazizi, M; Barakat, S; Ouimet, MA; Rosario-Meléndez, R; Fiorellini, JP; Graves, DT; Uhrich, KE “Impact of Locally Delivered Salicylic Acid from a Poly(anhydride-ester) on Bone Regeneration in Diabetic Rats” J Controlled Release 171 (1) 33-37 (2013).

Ouimet, MA; Griffin, J; Carbone-Howell, AL; Wu, WH; Stebbins, ND; Di, R; Uhrich, KE “Biodegradable Ferulic Acid-containing Poly(anhydride-ester): Degradation Products with Controlled Release and Sustained Antioxidant Activity”, Biomacromolecules 14 (3) 854-861 (2013).

Rosario-Mendelez, R; Ouimet, MA; Uhrich, KE “Formulation of salicylate-based poly(anhydride-ester) microspheres for short- and long-term salicylic acid delivery”, Polym Bull, 70 343-351 (2012).

Ouimet, MA; Snyder, S; Uhrich, KE “Tunable drug release profiles from salicylate-based poly(anhydride-ester) matrices using small molecule admixtures”, J Bioactive Compatible Polymers, 27 (6) 540-549 (2012).

Rosario-Meléndez, R; Harris, CL; Delgado-Rivera, R; Yu, L: Uhrich, KE “PolyMorphine: an innovative biodegradable polymer drug for extended pain relief”, J Controlled Rel, 162 (3) 538-544 (2012).

Hehir, S; Plourde, NM; Gu, L; Poree, DE: Welsh, W; Moghe, PV; Uhrich, KE “Carbohydrate Composition of Amphiphilic Macromolecules Influences Physicochemical Properties and Binding to Atherogenic Scavenger Receptor A”, Acta Biomat, 8, 3956-3962 (2012).

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).


Recent Patents

Uhrich, KE “Therapeutic polyesters and polyamides”; US PN 8,221,790 (issued July 17, 2012)

Uhrich, KE; Tian, L “Micelle Assemblies”; US PN 8,192,754 (issued June 5, 2012)

Uhrich, KE “Therapeutics Compositions and Methods”; US PN 8,088,405 (issued January 3, 2012)

Uhrich, KE “Polyanhydrides with Therapeutically Useful Degradation Products”; US PN 8,017,714 (issued September 13, 2011)


Research Area(s): 
Materials Chemistry
Organic Chemistry