Pharmaceutics, Pharmacology & Toxicology

Protein Binding

PI -Mariana Babayeva, MD, PhD, Associate Professor, Pharmaceutical and Biomedical Sciences

Plasma protein binding is one of the determinants of a drug’s therapeutic effect. Drugs in the body exist in two forms bound and unbound (free). Bound drugs do not elicit a therapeutic response because bound drugs are not dynamically distributed to target organs and don’t have affinity to target receptors. However, free drugs reach their active sites, interact with receptors and produce therapeutic effect.

Plasma protein binding interactions are categorized as displacement reactions. The consequence of the drug-drug reaction is increased free plasma concentrations of the displaced medication. Outcome of the protein binding interaction can be dangerous if the displaced medication is highly bound to blood proteins. Additional clinical risks include nonlinearpharmacokinetics and/or narrow therapeutic window of the affected drug. Such drug-drug interaction may lead to exaggerated therapeutic response as well as to acute and chronic toxicity. For this reason, each drug interaction is unique and should be analyzed on a case-by-case basis.

Spandaha, V., Jihong, L., Nedelman, M., Babayeva, M., Coller, B.S. (2018) Pharmacokinetic (PK) and Pharmacodynamic (PD) Studies of RUC-4 Succinate, a Novel αIIbβ3 Pure Antagonist for First Point of Contact Treatment of ST Segment Elevated Myocardial Infarction. Blood. http://www.bloodjournal.org/content/132/Suppl_1/1243.

Alexander, S, Flores, J, Ofuluozor H., Babayeva M. (2018) Significant Inhibition of Protein Binding of Phenytoin.Journal of Advances in Medicine and Medical Research. Vol.: 25(11) 1-7

Flores, J, Alexander, S, Babayeva, M (2018)A Novel HPLC Method for Determination of Phenytoin in Human Plasma. Journal of Pharmaceutical Research International, Vol.: 22(6)

Alexander, S., Flores, J., Ofuluozor, H., Babayeva, M (2018) Significant Inhibition of Protein Binding of Phenytoin. Journal of Advances in Medicine and Medical Research. Vol.: 25(11)1-7

Biofilms: Chemical and Biological Intervention

PI -Zvi Loewy, PhD, Associate Dean of Research, Professor, Pharmaceutical and Biomedical Sciences, Immediate Past Dean

Innovative medical devices have enhanced health care and improved the overall quality of life. Although providing significant medical benefits, there are unfortunately a myriad of diseases that can be attributed to the presence of medical devices. Microbes can colonize on a medical device surface and cause infections, and at times can even lead to malfunction of the device. Microbial species are present either as planktonic cells or incorporated into biofilms. Biofilms evolve from the planktonic state and are characterized as dense micro-communities that grow on inert surfaces and encapsulate themselves with secreted polymers. When organisms form a biofilm, they are able to adapt to environmental change by altering their gene expression patterns. The biofilm structure and corresponding change in gene expression can protect the microbes from disinfectant agents or antibiotics. The resultant biofilm can pose a serious public health issue.

While different types of medical devices harbor biofilms, dental prostheses are some of the most pervasive. The majority of the oral microbes are commensal organisms. Those that are pathogenic microbes can result in oral infections, and at times initiate systemic diseases. The physical nature of biofilms and the survival mechanisms they possess, whether phenotypic adaptability or genetic resistance, leave them impervious to antibiotic treatment. Given the lack of response to traditional antimicrobial therapy, biofilm infections currently pose a great challenge to the world of medicine and odontology.

Despite the difficulty of eradicating biofilms, several conventional strategies do exist to control them. Methods to remove the biofilms include mechanical, chemical or biologic. Our studies focus on (a) evaluating the existing chemical methods and identifying novel activities and benefits associated with the chemical methods and (b) the application of novel natural products to elicit unique anti-biofilm activities.

Loewy, Z.G., Galbut, S., Loewy, E. and Felton, D. (2018) Influence of the oral microbiome on general health. Dx.doi.org/10.5772/intechopen.76213.

Berger, D., Rakhamimiova, A, Pollack, A. and Loewy, Z. (2018) Oral Biofilms: Development, Control and Analysis. High-Throughput 7, 24, doi: 10.3390/ht7030024.

Loewy, Z. (2018) Nature: A Rich Source of Potent Therapeutics. Drug Design Development and Delivery Journal doi: 10.3102/ddddj.20181102.

Offenbacher, S., Barros, S., Bencharit, S., Yu, N., Preisser, J., Moss, K. and Loewy, Z.G. (2019) Differential mucosal gene expression patterns in Candidiasis-associated, chronic oral denture stomatitis. J. Prosthodontics doi:10.1111/JOPR 13007.

Phytochemicals and Cell Death

PI -Sid D. Ray, PhD, FACN, Interim Chair and Professor, Pharmaceutical and Biomedical Sciences

Dr. Ray’s research interests focus on two related areas. The first is exploring molecular mechanisms involved in drug and chemically-induced cell injury and cell death in in vivo models. The importance of cell death (apoptotic, necrotic, apocrotic and autophagic) remains fundamental to normal biological functions, and to the processes underlying key diseases, Parameters focused on to explore cell death are: specific genes, such as, bcl-2, bcl-xl, p53, bad, bax and interplay of free radicals and oxidative stress. Another evolving interest along these lines is the changing microRNA dynamics during pharmacologic and toxicologic interactions. All these are of considerable relevance to translational biomedical research.

The second is how naturally occurring phytochemicals relieve, prevent and/or reverse drug-induced cell injury and cell death. Phytochemicals and their mixtures selectively influence intracellular molecular targets and show antitoxic, anticancer and numerous other health-promoting properties. In recent years, we have explored role of curcumin and its bioavailability in several model systems. Experimental work conducted by our group was able to pinpoint major discrepancies regarding curcumin’s bioavailability in the published literature. Overall, several of our discoveries served as milestones in the fields of pharmacology, molecular toxicology, nutrition and safety sciences.

Stohs SJ, Chen CYO, Preuss HG, Ray SD, Bucci LR, Ji J ,and Ruff KJ
The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study
BMC Complement Altern Med. 2019; 19: 293. doi:10.1186/s12906-019-2699-x

Protective effects of the resveratrol analog piceid in dopaminergic SH-SY5Y cells.
Potdar S, Parmar MS, Ray SD, Cavanaugh JE. Arch. Toxicol. 2018; 92(2):669-677.doi:10.1007/s00204-017-2073-z.

Parmar MS, Syed I, Gray JP, Ray SD.
Curcumin, Hesperidin, and Rutin Selectively Interfere with Apoptosis Signaling and Attenuate Streptozotocin-Induced Oxidative Stress-Mediated Hyperglycemia.
Curr Neurovasc Res. 2015; 12(4):363-74.

Lahoti TS, Patel D, Thekkemadom V, Beckett R, Ray SD.
Doxorubicin-induced in vivo nephrotoxicity involves oxidative stress-mediated multiple pro-and anti-apoptotic signaling pathways.
Curr Neurovasc Res. 2012; 9(4):282-95.

Bulku E, Stohs SJ, Cicero L, Brooks T, Halley H, Ray SD.
Curcumin exposure modulates multiple pro-apoptotic and anti-apoptotic signaling pathways to antagonize acetaminophen-induced toxicity. 
Curr Neurovasc Res. 2012; 9(1):58-71.

Syed I, Rathod J, Parmar M, Corcoran GB, Ray SD.
Matrix metalloproteinase-9, -10, and -12, MDM2 and p53 expression in mouse liver during dimethylnitrosamine-induced oxidative stress and genomic injury.
Mol Cell Biochem. 2012; 365(1-2):351-61. doi: 10.1007/s11010-012-1277-z.

Pharmacogenomics

PI -Zvi Loewy, PhD, Associate Dean of Research, Professor, Pharmaceutical and Biomedical Sciences, Immediate Past Dean

Pharmacogenomic testing has been designed to help achieve optimal treatment outcomes. Our clinical research is focused on assessing the impact of pharmacogenomic testing on physicians' choice in prescribing medications. Current clinical areas include pain management and cardiovascular disease.

Pokotylyuk, I., Kulshrestha, S., Loewy, Z. and Kumar, P. (2018) Clinical relevance of μ-opioid receptor A118G polymorphism in demographically variant populations. Pharmacology and Toxicology 6: 228-236.

Chumki, S.R., Azzi, B. and Loewy, Z.G. (2019) The Dawn of Personalized Medicine: The Role of the Pharmacist. Journal of Precision Medicine 5: 29-35.

Coriolan, S., Arikawe, N., Moscati, A., Zhou, L., Dym, S., Donmez, S., Garba, A., Falbaum, S. Loewy, Z., Lull, M., Saad, M., Shtaynberg, J., and Owusu Obeng, A. (2019) Final Year Student pharmacists’ attitudes and perceptions towards pharmacogenomics education and their readiness to adopt it in their practice. American Journal of Health-System Pharmacy 76: 836-845.