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Investigation of Inter-Individual Variability in Monoclonal Antibody Disposition
(State University of New York at Buffalo, 2018)
Substantial inter-individual variability (IIV) in monoclonal antibody (mAb) pharmacokinetics has been reported in the clinic. The sources of variability are not well understood and often not explored. Very few preclinical ...
Machine Learning and Network-Based Systems Toxicology Modeling of Chemotherapy-Induced Peripheral Neuropathy
(State University of New York at Buffalo, 2018)
The overarching goal of my thesis work was to utilize the combination of mathematical and experimental models towards an effort to resolve chemotherapy-induced peripheral neuropathy (CIPN), one of the most common adverse ...
Optimized Engineering Platform for the Generation of Recycling Therapeutic Antibodies
(State University of New York at Buffalo, 2019)
A new modality in antibody engineering has emerged in which the antigen affinity is designed to be pH dependent (PHD). In particular, the combination of high affinity binding at neutral pH with low affinity binding at ...
Challenges Facing the Subcutaneous Administration of Therapeutic Monoclonal Antibodies
(State University of New York at Buffalo, 2019)
As an ever increasing number of therapeutic antibodies are being formulated and designed for subcutaneous (SC) dosing, it is an ever growing importance to understand the complexities of this route of administration. The ...
Megalin, Cubilin, and FcRn Expression in Type 2 Diabetes: Implications for Pharmaceutics and Diabetic Kidney Disease
(State University of New York at Buffalo, 2019)
Monoclonal antibodies (mAbs) continue to lead protein therapeutics. However, very few studies have examined the impact of diabetes mellitus (DM), one of the most frequent disease states worldwide, on mAb disposition. ...
Toxicodynamic and Toxicokinetic Based Treatment of γ-Hydroxybutyric Acid (GHB) Overdose
(State University of New York at Buffalo, 2019)
γ-Hydroxybutyric acid (GHB) is a short chain fatty acid which was first discovered through its synthesis in 1874, and later found to be an endogenous compound in the human central nervous system. GHB is a structural analogue ...
Deorphanizing Monocarboxylate Transporter 6: Evidence of Functional Roles in Lipid Metabolism and Drug Transport
(State University of New York at Buffalo, 2019)
Monocarboxylate transporters (MCTs) are members of the solute carrier 16 (SLC16) family of transporter proteins that are responsible for wide range of essential physiological processes. In total, there are fourteen isoforms ...
Pharmacokinetics and Receptor-Mediated Pharmacodynamics of Methylprednisolone
(State University of New York at Buffalo, 2019)
The corticosteroids possess substantial anti-inflammatory and immunomodulatory activity. Prolonged use of these drugs are, however, associated with adrenal suppression and other dose-limiting metabolic toxicities, manifested ...
Pharmacokinetics-Pharmacodynamics Based Investigations to Support the Development of Antibody-Drug Conjugates
(State University of New York at Buffalo, 2019)
Antibody-drug Conjugates (ADCs) are one of the fastest growing class of anticancer therapeutics, which consists of monoclonal antibodies (mAbs) covalently bound to highly potent chemotherapeutic agents (payloads) via ...
Engineered Antibody Fragments Targeting Chemokine Receptors to Modulate Macrophage Phenotype for Tumor Inhibition
(State University of New York at Buffalo, 2019)
In Chapter I we give a perspective and comprehensive review on design principles of targeted nanocarriers with an emphasis on improving clinical translation. We discuss membrane fluidity and spatial control of ligand ...