Unit: Drug Discovery and Development
Harrison College of Pharmacy
257 Pharmacy Research Building
Auburn, AL 36849
Member: Auburn University Research Initiative in Cancer (AURIC), Auburn, Alabama, 2012-present
Director: Auburn University Specialized Pharmaceutical and Experimental Center for Translational Research and Analysis (SPECTRA) core facility, at Harrison College of Pharmacy, 2013-present
Adjunct Professor: Department of Small Animal Medicine and Surgery, School of Veterinary Medicine, The University of Georgia, Athens, Georgia, 2012-present
Adjunct Professor: Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, 2018-present
Senior Scientist: UAB O’Neal Comprehensive Cancer Center, Member - Experimental Therapeutics, Birmingham, Alabama, 2019-present
Professor (tenured)*: Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, Alabama, 2018-present* - Primary Appointment
Integrating bioengineering tools, genome-wide genetic screens, and in vivo models to discover new determinants of triple-negative breast cancer cell invasion
Funder: Breast Cancer Alliance (BRCA) Exceptional Project Grant
Date: 12/1/2001 - 11/30/2022
Total Cost: $68,414
Unraveling the mechanism of acai BDS-anticancer drug interaction: A preliminary approach
Funder: NIH, 1 R15 AT011047-01A1
Total Cost: $440,352
Novel size-changing, a gadolinium-free contrast agent for magnetic resonance angiography
Funder: NSF, STTR Phase I, 2052242
Role: PI (AU Subcontract)
Total Cost: $256,000
Overview - Dr. Arnold is an industrial (Wyeth-Ayerst Research) and academically (University at Buffalo and Roswell Park Cancer Institute) trained pharmaceutical scientist with >20 years of expertise in experimental therapeutics and nanomedicine. Specifically, his laboratory is focused on developing and optimizing dosing schedules and novel composite lipid-nanoparticles as drug carriers. His research aims to gain insights into how dosing schedules and nanomedicines can be used to improve drug delivery, modulate drug exposure profiles, and improve drug treatment. His laboratory utilizes a variety of in vitro (2D and 3D) single-cell and multicellular tumor mimetics, in vivo (xenograft, orthotopic, and metastatic) models of human cancers (including, prostate, breast, brain, melanoma, and pancreatic) and applies non-compartmental and computational approaches to support the pharmacokinetic-pharmacodynamic (PK-PD) analysis, modeling and simulation of existing and investigational agents, and nanomedicines.
Furthermore, contemporary molecular techniques (RNA-seq, single-cell analysis, CRISP, etc.) are used to gain insights into disease progression, and how tumor microenvironment and alternate dosing schedules can alter the disposition and activity of therapeutic agents and nanomedicines. In addition to using conventional bioanalytical methods that employ liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), his laboratory uses a variety of optical techniques (bioluminescent, fluorescent, and multispectral optoacoustic tomography; IVIS and IThera MSOT) and magnetic resoncace imaging (MRI) to non-invasively determine tumor growth, drug/carrier distribution and treatment/toxic mediated-effects.
Development of Nanomedicines for Treatment of Prostate Cancer and Tumor Imaging - The overall goal of Dr. Arnold’s research program has been focused on exploiting differences in the pathophysiology of disease states, specifically cancers, with the development and optimization of nano-particulate based strategies to improve detection and treatment of disease. Early in his career, he demonstrated that repetitive administration of pegylated, long-circulating liposomes containing doxorubicin enhanced the permeability of brain tumors to subsequent treatments. This work laid the foundation for developing concomitant therapies that exploit this “window” of opportunity and provided mechanistic insights into biodistribution and exposure profiles of different drugs and drug carriers. Over the last 10 years, I have secured an R21 (MPI) and an R01 (PI), focusing on gaining insights into strategies that alter the rate and extent of drug release and particulate uptake in prostate cancer. My laboratory has also collaborated on developing and using hyperthermia-based magnetic nanoparticles, novel imaging techniques (NSF STTR), and 3D tumor micro mimetic systems (R43 and R44 w/CFDRC Huntsville, AL). Overall, my laboratory is conducting research critical to understanding cancer biology to improve drug delivery and achieve optimal exposure profiles.
Experimental Therapeutics (PK) and Dose Optimization - Dr. Arnold’s laboratory uses pharmacokinetic (PK) and pharmacodynamic (PD) principles as tools for the selection of novel therapeutic agents, investigation of drug interactions, and rational design of passively and actively targeted drug delivery systems. His laboratory uses a variety of laboratory and computational approaches to describe drug kinetics and biodistribution, establish exposure-response relationships, develop PK/PD models and conduct simulations to evaluate potential dosing schedules, look for evidence of drug-drug interactions (DDI), and/or the development of novel hypotheses. Utilizing his PK/PD analysis expertise, he has evaluated the disposition of investigational agents, botanical mixtures, and complex nanomedicines. Studies have examined the effect of food on drug PK, looked at drug-drug interactions, and used population and mechanistic computational modeling to examine factors that control the distribution of TocosolTM, a nano-emulsion containing paclitaxel in humans, and correlated exposure to antitumor activity and toxicity. These approaches have also been applied to a variety of collaborators examining the effects of antagonists on drug efflux proteins drug-drug interactions and collaborating with veterinarians working on translating FDA-approved drugs for humans to various companion and exotic (zoo and wildlife) animals.
CNS Disorders, Drug Toxicity and Treatment - Dr. Arnold’s initial research focused on the effect of drug encapsulation into long-circulating, lipid-based nanoparticles (pegylated liposomes) on the barrier properties of the blood tumor brain barrier (BTBB) as well as its effect on normal blood-brain barrier (BBB). Utilizing both classical bioanalytical measures (HPLC, LC-MS/MS) and small animal non-invasive imaging (MRI), he demonstrated how repetitive dosing altered blood flow and resulted in enhanced uptake of the brain. Since then, he has consulted with academic and industrial researchers interested in developing therapies for CNS diseases/disorders and drug toxicity. My laboratory has shown the impact of repetitive dosing of nanoparticles, carrying anticancer agents, on brain penetrance, BBB compromise, as well as neurotoxicity and cardiotoxicity using a variety of small animal (mouse and rat) models.