Title: Assistant Professor
Department: Department of Pharmaceutical Sciences
School/Center: School of Pharmacy
Office Location: 110 Mugar
Phone: 617.373.3091
Fax: 617.373.8886
Email: r.campbell@neu.edu
Education:
Bachelors in Biology, Chemistry
Niagara University, NY
PhD, Molecular and Cellular Biophysics/ Pharmaceutics,
Roswell Park Cancer Institute /SUNY @ Buffalo, Buffalo, NY
Postdoctoral Research Fellow
Department of Radiation Oncology
Massachusetts General Harvard Medical
Specializations:
Identifying, and overcoming, tumor cellular barriers for cancer therapy
In vitro screening & in vivo efficacy evaluation of nano-liposomal therapeutics
Biophysical evaluation of the effects of lipids, cytotoxic drug compounds and excipients on the physicochemical properties of cellular and nano-delivery systems
Research:
Overcoming Cellular Barriers to Cancer Therapy
In an effort to develop more effective treatments for cancer therapy, we should understand the general factors limiting chemotherapeutic drug effects during therapy. For e.g., many barriers on the physiological level (i.e., tumor hypertension, high collagen content, and long interstitial transport distances in tumors) limit chemotherapeutic drug effects. In our lab, we have now discovered that these barriers exist not only on the physiological level, but at the cellular level as well. One barrier effect (produced at the cellular level) has been shown to limit the effectiveness of well-known chemotherapeutic drugs used routinely for the treatment of human pancreatic cancer. This drug barrier effect is caused by the expression of mucin. Mucin is a glycoprotein over-expressed by human pancreatic tumor cells (and more abundantly in pancreatic tumors). Our lab has discovered that the normal synthesis of mucin glycosylation in pancreatic cells results a mesh protecting pancreatic cancer cells from drug therapy. We have demonstrated that inhibition of mucin type-O-glycosylation in pancreatic tumor cells significantly improved the antineoplastic drug effects of conventional chemotherapeutic agents in vitro and in vivo. We now seek to establish all mechanism(s) involved in the beneficial strategy, to extend the approach for treatment of other mucin-expressing tumors and to achieve the most desirable therapeutic results with minimal potential harm to patients.
Vascular Targeting for Cancer Therapy
An understanding of accessible tumor vascular targets is key to the successful development of innovative strategies using this treatment approach. Many chemotherapeutic agents are delivered to tumors in a non-specific manner, often resulting in uncontrollable tumor growth & distant metastases and toxicity caused to normal tissues. In order to stop the spread of harmful metastatic disease, we now seek to selectively deliver drugs to tumors with support from drug carrier molecules. We now focus on developing new formulations and improving their potential to target tumor vessels & angiogenesis. In this way we limit the flow of oxygen and nutrients to viable cancer cells that depend on uninterrupted blood flow for survival. We consider specialized vascular features during the process of formulation development. For example, blood vessels are lined with glycosaminoglycans and proteoglycans (and many other negatively charged functional molecules). For this reason, drugs are now being incorporated into positively-charged (cationic) liposomes to enhance delivery to this site of drug action. Our group has made seminal contributions to this field of study. We are currently developing, characterizing and evaluating innovative cationic liposome therapeutics for the treatment of various human cancers. The MAGNETIC DRUG TARGETING (MDT) has been re-developed in our lab to improve our efforts to target tumor vessel. We have developed MAGNETIC CATIONIC NANO-SYSTEMS capable of responding to an externally applied magnetic field. The approach improves interaction of nanosystems with the tumor vascular supply. Our approach is creating additional opportunities for cancer therapy.
General Techniques
Conventional biophysical and contemporary pharmaceutical techniques are used. Some include HPLC, spectrofluorometric/ cytotoxicity & immuno-histochemistry assays. Others include DIC/fluorescence/ Intravital microscopy, and differential scanning calorimetry, zeta potentiometry & particle size analyses. These are routinely used in the discovery and in formulation development, as well as a host of different in vitro screening procedures. We largely rely on studies that investigate the intracellular fate of novel drug delivery systems. Endpoint studies (i.e., RT-PCR, blot analyses) are used to correlate efficacy with molecular endpoints.
* See publications below for references
Publications:
1. Kalra, A. and Campbell, R. B. Mucin overexpression limits the effectiveness of 5-FU by reducing intracellular drug uptake and antineoplastic drug effects in pancreatic tumors. European Journal of Cancer, 45: 164-173, 2009.
2. Campbell, R. B., Ying, B., Kuesters, G. M., and Hemphill, R. Fighting cancer: from the bench to bedside using second generation cationic liposomal therapeutics. Journal of Pharmaceutical Sciences, 98: 411-429, 2009.
3. Dabbas, S., Kaushik, R. R., Dandamudi, S., Kuesters, G. M., and Campbell, R. B. Importance of the liposomal cationic lipid content and type in tumor vascular targeting: physicochemical characterization and in vitro studies using human primary and transformed endothelial cells. Endothelium, 15: 189-201, 2008.
4. Campbell, R. B. Battling tumors with magnetic nanotherapeutics and hyperthermia: Turning up the heat. Nanomedicine, 2, 2007.
5. Dandamudi, S. and Campbell, R. B. Development and characterization of magnetic cationic liposomes for targeting tumor microvasculature. Biochimica et Biophysica Acta, 1768: 427-438, 2007.
6. Dandamudi, S. and Campbell, R. B. The drug loading, cytotoxicity and tumor vascular targeting characteristics of magnetite in magnetic drug targeting. Biomaterials, 28: 4673-4683, 2007.
7. Kalra, A. V. and Campbell, R. B. Mucin impedes cytotoxic effect of 5-FU against growth of human pancreatic cancer cells: overcoming cellular barriers for therapeutic gain. British Journal of Cancer, 97: 910-918, 2007.
8. Campbell, R. B. Tumor physiology and delivery of nanopharmaceuticals. Anti-cancer agents in Medicinal Chemistry, 6: 501-510, 2006.
9. Kalra, A. V. and Campbell, R. B. Development of 5-FU and doxorubicin-loaded cationic liposomes against human pancreatic cancer: Implications for tumor vascular targeting. Pharm Res, 23: 2809-2817, 2006.
