Lab: 848-445-5630 (WRL 371)
Office: Wright Rieman Labs, Rm 311 (Busch)
Mail: Chemistry & Chemical Biology, 610 Taylor Road, Piscataway, NJ 08854
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.
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.
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.
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 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 the American Chemical Society, 2014
- 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
Tao, L; Faig, A; Uhrich, KE “Liposomal Stabilization Using a Sugar-based, PEGylated Amphiphilic Macromolecule”, J Coll Interf Sci, 431 (2014) 112–116 http://dx.doi.org/10.1016/j.jcis.2014.06.004
Stebbins, ND; Ouimet, MA; Uhrich, KE “Antibiotic-containing polymers for localized, sustained drug delivery”, Adv Drug Delivery Rev, (2014) [invited]. 10.1016/j.addr.2014.04.006
Carbone-Howell, AL; Stebbins, N; Uhrich, KE “Poly(anhydride-esters) Comprised Exclusively of Naturally-occurring Antimicrobials and EDTA: Antioxidant and Antibacterial Activities”, Biomacromolecules, 15 (5) 1889–1895 (2014). 10.1021/bm500303a
Gu, L; Nusblat, LM; Tishbi; N; Noble, SC; Pinson, CM; Mintzer, E; Roth, CM, Uhrich, KE “Cationic Amphiphilic Macromolecule (CAM)-lipid Complexes for Efficient siRNA Gene Silencing”, J Control Rel, 184 (28) 28-35 (2014). 10.1016/j.jconrel.2014.04.005
Prudencio, A; Stebbins, ND; Johnson, M; Song, MJ; Langowski, BA; Uhrich, KE “Polymeric Prodrugs of Ampicillin as Antibacterial Coatings”, J Bioact Compat Polym, 29 (3) 208-220 (2014). 10.1177/0883911514528410
Abdelhamid, D; Arslan, H, Uhrich, KE “Role of Branching of Hydrophilic Domain on Physicochemical Properties of Amphiphilic Macromolecules”, Polym Chem, 5 (4), 1457-1462 (2014) 10.1039/C3PY01072D [invited].
Delgado-Rivera, R; Rosario-Meléndez, R; Yu, W; Uhrich, K “Biodegradable Salicylate-Based Poly(anhydride-ester) Microspheres For Controlled Insulin Delivery”, J Biomed Mater Res: A (2013) published online : 24 SEP 2013. 10.1002/jbm.a.34949 PMID: 24027012 PMCID: PMC3952025
Rosario-Melendez, R; Yu, W; Uhrich, K “Biodegradable polyesters containing ibuprofen and naproxen as pendant groups”, Biomacromolecules, 14 (10) 3542-3548 (2013). 10.1021/bm400889aPMID: 23957612
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).
Uhrich, KE; Rosario-Melendez, R “Slow-degrading Polymers for Undelayed and Sustained Drug Delivery”; US PN 8,741,317 (issued 06/03/14)
Uhrich, KE and Carbone A “Iodinated polymers”; US PN 8,361,453 (issued 01/29/13)
Uhrich, KE and Kim, YM “Fast degrading polymers”; US PN 8,263,060 (issued 09/11/12)
Uhrich, KE “Therapeutic polyesters and polyamides”; US PN 8,241,668 (issued 08/14/12)
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)