Lab: 848-445-5630 (WRL 371)
Office: Wright Rieman Labs, Rm 311 (Busch)
Mail: Chemistry & Chemical Biology, 610 Taylor Road, Piscataway, NJ 08854
The UGroup laboratory centers on polymeric bioactives; specifically, the design of biocompatible, biodegradable polymers that can improve human health. Given that our starting materials are naturally occurring and our polymeric bioactives safe, we incorporate 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 (e.g., patents) and industrial collaborations as it pertains to our published research in bioactive delivery.
Bioactive Polymers: Amphiphilic 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 uptake of LDL and inhibit athero-inflammation. We now design anti-atherogenic polymers that target macrophage receptors and mitigate low-density lipoprotein (LDL) uptake.
Regarding bioactivity, the AMs specifically inhibit the uptake of "bad cholesterol" (i.e., LDL). 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 new bioactive polymers that can potential reverse atherogenesis.
With their ability to quickly migrate into the nucleus, we continue to optimize the AMs for delivery of genes (i.e., 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 (i.e., lipopolyplexes) 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 Bob Prud'homme (Princeton, Chemical Engineering), the AMs are kinetically entrapped into nanoparticles via flash precipitation such that AMs are stabilized in serum over extended time periods.
Polymers from Bioactives: PolyActives
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), many other drug classes have been investigated, including antiseptics, antioxidants, antimicrobials, and opiates.
For example, by chemically incorporating morphine into a polymer (i.e., 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.
With funding from NIH, we are developing NSAID-based polymers that locally deliver salicylic acid to promote bone regeneration. In our collaboration with Pat O'Connor (Rutgers, 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 (Uni Sao Paulo, Chemistry), stable hydrogels are fabricated by admixing NSAIDS that release over days (rather than hours).
Currently, we are exploring polymers that incorporate bioactives of interest to our industrial partners (e.g., Chanel). With Polymer Therapeutics (PRx), we are developing the PolyAspirin technology into wound care devices, such as sutures.
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
- Ouimet, MA; Faig, JJ; Yu, W; Uhrich, KE “Ferulic acid-based polymers with glycol functionality as a versatile platform for topical applications”, Biomacromolecules, accepted. 10.1021/acs.biomac.5b00824
- Mitchell, A; Kim, B; Snyder, S; Uhrich, KE; O’Connor, JP “Use of Salicylic Acid Polymers and rhBMP-2 to Promote Bone Regeneration in Rabbit Parietal Bone Defects”, J Bioactive Compat Polym, accepted.
- Chan, JW; Zhang, Y; Uhrich, KE “Amphiphilic Macromolecule Self-Assembled Monolayers Suppress Smooth Muscle Cell Proliferation" Bioconj Chem for Special Issue: Biofunctional Biomaterials: The Third Generation of Medical Devices, online. [invited] 10.1021/acs.bioconjchem.5b00208
- Demirdirek, B; Uhrich, KE “Salicylic acid-based pH-sensitive hydrogels for oral insulin delivery”, J Drug Targeting, accepted. [invited] 10.3109/1061186X.2015.1073293
- Subramanian, S; Mitchell, A; Yu, W; Engler, S; Uhrich, K; O'Connor, J “Salicylic Acid-based Polymers for Guided Bone Regeneration using Bone Morphogenetic Protein-2”, Tissue Eng: Part A, 21(13-14):2013-2024 (2015).
- Stebbins, ND; Faig, JJ: Yu, W; Guliyev, R; Uhrich, KE “PolyActives: Controlled and Sustained Bioactive Release Via Hydrolytic Degradation”, Biomater Sci, 3, 1171 – 1187 (2015). [invited] 10.1039/C5BM00051C
- Stebbins, ND; Yu, W; Uhrich, KE “Enzymatic Polymerization of an Ibuprofen-containing Monomer and Subsequent Drug Release”, Macromol Biosci, accepted (2015). 10.1002/mabi.201500030
- Garber L; Jingar, N; Rosario-Meléndez, R; Uhrich, KE “Tuning Salicylate-Based Polymers to Overcome Lag Time and Extend Release via Copolymers and Polymer Blends”, J Polym Sci, Polym Phys, 53 (10) 685-689 (2015); 10.1002/polb.23690
- Yu, W; Bien-Aime, S; Li, J; Zhang, L; McCormack, ES; Goldberg, ID; Uhrich, KE: Narayan, P “Injectable Microspheres for Extended Delivery of Bioactive Insulin and Salicylic Acid”, J Bioactive Comp Polym, 30, 340-346 (2015); 10.1177/0883911515569919
- Snyder, SS; Anastasiou, TJ and Uhrich, KE " In vitro degradation of an aromatic polyanhydride with enhanced thermal properties”, Polymer Degrad Stability, 115, 70-76 (2015); 10.1016/j.polymdegradstab.2015.02.002
- Martin, AAT; Tomasini, M; Kholodovych, V; Gu, L; Sommerfeld, SD; Uhrich, KE; Murthy, NS; Welsh, WJ; Moghe, PV “Carbohydrate-derived amphiphilic macromolecules: A biophysical structural characterization and analysis of binding behaviors to model membranes” J. Funct. Biomater. 2015, 6, 171-191; doi:10.3390/jfb6020171
- Abdelhamid, D; Zhang, Y; Lewis, DR; Moghe, PV; Welsh, WJ; Uhrich, KE “Tartaric Acid-based Amphiphilic Macromolecules with Ether Linkages Exhibit Enhanced Repression of Oxidized Low Density Lipoprotein Uptake”, Biomaterials, 53, 32-39 (2015). 10.1016/j.biomaterials.2015.02.038
- Lewis, DR; Petersen, LK; York, AW; Zablocki, KR; Joseph, LB; Kholodovych, V; Prud’homme, RK; Uhrich, KE; Moghe, PV “Sugar-based Amphiphilic Nanoparticles Arrest Atherosclerosis In Vivo”, Proc National Acad Sci, 112 (9) 2693-2698 (2015); 10.1073/pnas.1424594112
- Bien-Aime, S; Uhrich, KE “Polyanhydride Synthesis” section under “Polycondensations”, Pugh, C, Section Editor in Encyclopedia of Polymeric Nanomaterials, Kobayashi, S; Muellen, K Editors-in-Chief, Springer: Germany, 2015; pp 1767-1772 [invited]. ISBN 978-3-642-29647-5
- Gu L, Faig A, Abdelhamid D, and Uhrich KE. “Sugar-based Amphiphilic Polymers for Biomedical Applications: from Nanocarrier to Therapeutic” Acc Chem Res, (10), 2867–2877 (2014) [invited]. 10.1021/ar4003009
- Ouimet, MA; Fogaça, R; Snyder, SS; Sathaye, S; Catalani, LH; Pochan, DJ and Uhrich, KE “Poly(anhydride-ester) and Poly(N-vinyl-2-pyrrolidone) Blends: Salicylic acid-releasing hydrogel that reduce inflammation”, Macromol Biosci, 15 (3) 342-350 (2015); 10.1002/mabi.201400238
- Petersen, LK; York, AW; Lewis, DR; Ahuja, S; Uhrich, KE; Prud’homme, RK; Moghe, PV "Amphiphilic Nanoparticles Repress Macrophage Atherogenesis: Novel Core/Shell Designs for Scavenger Receptor Targeting and Down-regulation", Mol Pharmaceutics, 11 (8), 2815–2824 (2014); 10.1021/mp500188g PMCID: PMC4144725
- Faig, A; Petersen, LK; Moghe, PV; Uhrich, KE “Impact of hydrophobic chain composition on amphiphilic macromolecule anti-atherogenic bioactivity”, Biomacromolecules, 15 (9) 3328–3337 (2014); 10.1021/bm500809f
- Rogers, MA; Yan, Y-F; Ben-Elazar, K; Lan, Y; Faig, J; Smith, K; Uhrich, KE “Salicylic acid (SA) Bioaccessibility from SA-based Poly(anhydride-ester)” Biomacromolecules, 2014, 15 (9), 3406−3411 (2014); 10.1021/bm500927r
- Tao, L; Faig, A; Uhrich, KE “Liposomal Stabilization Using a Sugar-based, PEGylated Amphiphilic Macromolecule”, J Coll Interf Sci, 431 (2014) 112–116; 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, 78 77-87(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 102A 2736-2742 (2014); 10.1002/jbm.a.34949
- Uhrich, KE; Sparks, SM; Gu, L; Harmon, A; Roth, CM; Federici, C “Amphiphilic Macromolecules for Nucleic Acid Delivery”; US PN 8,846,850,B2 (issued 09/30/2014)
- Uhrich, KE; Carbone, A and Prudencio, A “Biodegradable Polyanhydrides with Natural Bioactive Molecules”; AN 12/595,591 (filed 04/14/08); US PN 8,747,832 (issued 06/10/2014)
- Uhrich, KE; Rosario-Melendez, R “Slow-degrading Polymers for Undelayed and Sustained Drug Delivery”; US PN 8,741,317 (issued 06/03/2014)
- Uhrich, KE and Carbone A “Iodinated polymers”; US PN 8,361,453 (issued 01/29/2013)
- Uhrich, KE and Kim, YM “Fast degrading polymers”; US PN 8,263,060 (issued 09/11/2012)
- Uhrich, KE “Therapeutic polyesters and polyamides”; US PN 8,241,668 (issued 08/14/2012)