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William E. Bentley
Reza Ghodssi
Anjan Nan
Gregory Payne
Gary Rubloff
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The multidisciplinary research environment of the Nan Group laboratory provides expertise for the design, development and use of nanosystems for therapeutic purposes. Most of the group's effort is aimed at the development of novel nanoplatforms for controlled delivery of bioactive agents. Fabrication of platforms for localized drug delivery through the use of nanoscale materials is one way to advance the field of targeted delivery and, ultimately, improve patients' lives by improving the safety and efficacy of therapeutics.

At the Center for Nanomedicine and Cellular Delivery and Dr. Nan's laboratories, students and post doctoral fellows have ample opportunities to engage in the research on either side of the nano-bio border and well as in various ongoing multidisciplinary projects. Most students, in fact, choose to undertake more than one distinctly different interdisciplinary project during their graduate training in nanobiotechnology. As part of the Biochip Collaborative the Nan group is focused on the biological evaluation of novel candidate AI-2 inhibitor drugs that will be selected using microfabricated chip based screening as developed by the co investigators of this project. A major challenge to successful clinical translation of lead candidate drugs is their penetration through existing bacterial biofilms and reaching their intracellular target site.  Using novel drug delivery design and strategies such barriers can be overcome. For example covalent conjugation of drugs to a macromolecular nanocarrier such as liposomes, dendrimers or water-soluble polymeric backbones, it is possible to enhance permeation through biofilm, overcome bacterial drug resistance and enhance accumulation of drugs inside the bacterial cell. This has the potential to enhance efficacy of the drugs. Moreover targeted drug delivery minimizes the non-specific uptake of the drug by normal healthy organs and tissues of the body thereby minimizing drug associated toxicity.

In the long term the group's aim is to establish appropriate animal models of biofilm infection e.g. where biofilm-coated scaffold materials are implanted into mouse. Such in vivo models will be critical for determining the efficacy of any candidate drug compounds and associated drug delivery methods.

Aside from the Deutsch research collaborative, the following two areas are being actively explored:

Water-soluble Synthetic Polymers for Cancer Targeted Delivery

Delivery of bioactive agents using targetable water soluble polymeric carriers can on one hand increase organ/tissue/cell specific accumulation and on the other hand minimize toxicity by reducing non-specific uptake by normal organs. In our lab we focus on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers for targeted delivery to solid tumors. Clinically relevant cancer types are explored including breast and pancreatic carcinomas. The advantage of HPMA copolymers is that it is possible tailor the molecular weight and charge of these copolymers to alter biodistribution and minimize uptake by non-target organs. Additionally, covalent conjugation of drugs to HPMA backbone enhances solubility of drugs and improves their stability and disposition in the body. Biodegradable spacers are typically used to conjugate the drugs to the polymer backbone in order to control intracellular release.

Inorganic Silica Nanotubes for Controlled Drug Delivery

Recent advances in nanotechnology have enabled the fabrication of inorganic nanomaterial based delivery systems with well defined shape and discrete size, and surface chemistry. In a collaborative research initiative with Sang Bok Lee (Chemistry, UMCP) we are exploring the potential of magnetic silica nanotubes for image guided drug delivery. These "template synthesized" nanotubes provide unique features such as end functionalization to control drug release, inner voids for loading biomolecules, and distinctive inner and outer surfaces that can be differentially functionalized for targeting and biocompatibility. Our research specifically focuses on understanding the influence of size and surface charge of nanotubes on cellular toxicity and uptake mechanisms.

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Anjan Nan

Anjan Nan

Assistant Professor Anjan Nan received his B.S. in Pharmacy from Jadavpur University, India in 1996, and Ph.D. in Pharmaceutical Sciences from the University of Mississippi in 2002. After finishing his Ph.D., he worked as a Research Associate at the Department of Pharmaceutical Sciences at the University of Maryland Baltimore, where he accepted a faculty position in 2006. Dr. Nan is the co-Director of the Center for Nanomedicine and Cellular Delivery.

Dr. Nan's research interests include design and development of nanocarriers for drug delivery and imaging applications. Of particular interest are water-soluble polymer-drug conjugates for targeted cancer therapy and engineered inorganic silica nanotubes for image guided biomolecule delivery.

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Group Members' Areas of Research

Dr. Paul Dowell

Paul Dowell

In Vitro Evaluation of Candidate Anti-Biofilm Drugs

Dr. Dowell's current work is aimed at establishing in vitro biofilm assay systems and applying drug permeation enhancer methods to these systems. One goal is to establish an in vitro system with which to test the efficacy of candidate anti-biofilm drugs (e.g. LuxS/Pfs inhibitors) which have been identified through novel screening methods. A second goal is to apply drug delivery techniques to enhance the efficacy of these candidate drugs. A third goal is to establish an in vivo system with which to test the efficacy of candidate anti-biofilm drugs and associated drug delivery techniques. The long term goal of this project is to develop novel, effective therapies to combat treatment-resistant biofilm infections.

In Vivo Evaluation of Polymer-Drug Conjugates for Targeted Cancer Drug Delivery

This project is aimed at examining the efficacy and biodistribution of polymer-drug conjugates in colorectal and pancreatic tumor xenograft mouse model systems. The long term goal of this project is to develop efficacious cancer therapy treatments by attaching novel polymer moieties to existing and novel anti-cancer drugs.

Dr. Dowell (Ph.D., Molecular & Cellular Biology Program, Oregon State University) is a postdoctoral fellow at the University of Maryland School of Pharmacy. He holds B.S. in Biology/Genetics from the University of Kansas.

Dr. Vladimir Seregin

Vladimir Seregin

Antimicrobial Drug Delivery Device Fabrication

In medicine, the use of drug delivery systems, designed for organ or tissue-specific delivery of antibiotics, is a useful way to safely and selectively increase local drug concentration at the site of the infection. Whether these systems are based on polymers, dendrimers, liposomes or other constructs, they are rarely intended to increase a specific drug's penetration of bacteria's cell wall. The use of cell-penetrating drug delivery systems is typically limited to treating antibiotic-resistant bacterial stains. As part of the Biochip Collaborative, the goal of this project is to adapt existing antibiotic cellular drug delivery devices to transport candidate quorum sensing inhibitors (e.g. LuxS/Pfs inhibitors) which have been identified through novel screening methods. These will then be used to evaluate the antimicrobial efficacy of the selected drug candidates, which cannot be tested in vitro or in vivo with conventional permeation-enhancer methods.

Composite Nanoparticles for Targeted Delivery to Breast Solid Tumors

The objective of this research is to demonstrate that large quantities of anticancer agents can be safely and selectively delivered (and then released in a controlled manner) to Estrogen Receptor-negative (ER-) breast tumors using novel intelligent bi-particle nanotech drug delivery systems (nanoDDS). Currently, the work is focused on fabrication and assembly of the nanoDDS components: pH-sensitive elastic polymers and porous nanoparticles. The resulting nanoDDS with be designed for safe and effective delivery of large quantities of Adriamycin® (doxorubicin) and Taxol® (paclitaxel) directly to ER- breast tumors using assembled composite nanoparticles.

Dr. Seregin is a Research Associate at at the University of Maryland School of Pharmacy. He holds B.S. in Chemistry/Mathematics from Texas A&M University-Commerce, and a Ph.D. in Inorganic and Materials Chemistry from Texas Christian University.

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