Robert D. Arnold, Ph.D. Assistant Professor Pharmaceutical and Biomedical Sciences Office: Room 220, R.C. Wilson Pharmacy Phone: 706-542-6813 E-mail: rarnold@rx.uga.edu

Biosketch

B.S. Biochemistry	State University of New York	Plattsburgh, NY	1994
Scientist I	Wyeth-Ayerst Research	Rouses Point, NY	1994-1997
Ph.D., Pharmaceutical Sciences	University at Buffalo	Amherst, NY	2004

Post-doctoral Experience
Postdoctoral Associate, University at Buffalo & Roswell Park Cancer
Institute, Buffalo, NY, 2004-2005

Honors and Awards
AAPS - Student Development and Outreach Committee, 2005 - Present
Fellow - American Foundation for Pharmaceutical Education (AFPE)
Graduate student Symposium in Drug Delivery and Pharmaceutical Sciences Awards, AAPS National Meeting 2003
Pharmaceutical Sciences Graduate Scholar Award, University at Buffalo, 2002

Research Interests
Cancer Chemotherapy and Experimental Therapeutics of Antitumor, Antiangiogenic, and Tumor Antivascular Agents Biopharmaceutics, Pharmaceutics, Drug Delivery, Nanoparticulate Drug Carriers, Pharmacokinetics & Pharmacodynamics.

Cancer represents the 2nd leading cause of death in the U.S. The treatment of solid tumors fails in part due to physiological and pharmacological barriers. Poor perfusion, tortuous and impermeable vasculature, and drug resistance transporters are physiologic properties of tumors that limit drug extravasation, deposition, and retention. Advances in molecular biology have improved our understanding of the underlying causes of disease and increased the number of potential therapeutic targets. However, the efficacy of many available/novel antineoplastic agents is hindered by their poor physicochemical properties (e.g., membrane or issue penetration), short circulation time in vivo, and distribution to reactive non-target tissues (toxicity). Failure to deliver optimal quantities of antineoplastic agents and achieve uniform drug exposure to eradicate a tumor completely, often results in recurrence, metastasis, and development of therapeutic resistance. Furthermore, dose selection and development of chemotherapeutic dosing schedules for existing drugs is often empirical.

A broad goal of my laboratory is to utilize a systems approach to integrate the pathophysiology of a disease state with the known pharmacology of drugs to development optimal delivery systems for existing and novel therapies for cancer, and translate those findings from discovery and preclinical development to clinical use. We hypothesize that a multi-drug therapeutic approach employing hetero-functional nanoparticulate drug delivery systems that target diverse mechanisms of tumor growth will be most effective clinically at treating primary and metastatic disease. Our primary aims are to (i) determine the direct anti-tumor effect and ability of novel nanoparticulate drug carriers to limit tumor growth and metastases in vivo, (ii) gain insight in the molecular mechanisms of the antitumor/ vascular effects following acute (high-dose) and chronic (low-dose) protracted treatment, (iii) develop a mechanistic understanding of how long-circulating nanoparticulate drug carriers can be used and optimized to enhance conventional antitumor activity while mediating novel antivascular or antiangiogenic effects, (iv) examine the use of existing and novel tumor/vascular (e.g., Her-2, VEGF, etc.,) targeting moieties, (v) develop mathematical expressions (PK/PD-modeling) to describe drug exposure-response relationships, and use them to predict optimal drug dosing schedules and test new hypotheses, and (vi) determine the effect of acute and chronic concomitant administration of conventional (e.g., topotecan or doxorubicin) and selective tumor vascular acting agents (e.g., DMXAA or TNP-470) at high and low doses for the treatment of primary and metastatic disease.

Representative Publications
Arnold, R.D., Mager, D.E., Slack, J.E., and Straubinger, R.M. (2005) Effect of repetitive administration of doxorubicin-containing liposomes on plasma pharmacokinetics and drub biodistribution in a rat brain tumor model. Clin.Cancer Res., 11(24):8856-8865

Straubinger, R.M, Arnold, R.D., Rong, Z., Mazurchuk, R., and Slack, J.E., Antivascular and antitumor activities of liposome-associated drugs. (2004) Anticancer Research, 24(2A), pp. 397-404

Arnold, R.D., Slack, J.E., and Straubinger R.M., Quantification of doxorubicin and metabolites in rat plasma and small tissues by liquid chromatography electrospray tandem mass spectroscopy. Journal of Chromatography B, (2004) 808(2), pp. 141-152

Arnold, R.D., Zhou, R., Mazurchuk, R., Chau, R.I., and Straubinger R.M., Liposome Mediated Alterations in Tumor Vascular Permeability. AAPS PharmSci (2002) 4:W4105