University Events

Description: TITLE: DEVELOPING FLUORESCENT SENSORS FOR THE BIOIMAGING OF CHELATABLE IRON (II) IONS
Abstract: Therapeutic agents, in order to reach their target, frequently need to cross epithelial and endothelial sheets. Two routes are available for such purpose: the transcellular and the paracellular pathways. The former is employed by lipophilic drugs and by molecules selectively transported by channels, pumps and carriers present in the plasma membrane. Hydrophilic molecules cannot cross biological membranes, therefore their transepithelial transport could be significantly enhanced if they moved through the paracellular pathway. Transit through this route is regulated by tight junctions (TJs). The discovery in recent years of the molecular mechanisms of the TJ has allowed the design of different methods to open the paracellular route in a reversible manner. One such method is the use of chemical entities called bioenhancers, to promote and augment the bioavailability of the drugs which are mixed with them without exhibiting any synergistic effects. The need of the hour is to carry out extensive research on these bioenhancers so that they could be utilized in the drug formulations.

In this study we present the preliminary understanding of two different candidates, which have the potential to be used as a bioenhancer for hydrophilic molecules by enhancing paracellular transportation. Our first candidate was a type of herbally prepared silver nanoparticle (rajath bhasma), used in the ancient system of Ayurveda for several centuries as a part of a concoction including a mixture of medicinal herbs to treat a wide array of illnesses. The other candidate that was considered was an 80kDa novel botulinum neurotoxin type E (BoNT/E) neurotoxin associated proteins (P-80). In this work, we characterize structure and function of these candidates by using chemical, biochemical and biophysical techniques. In vitro studies indicated morphological and biochemical changes in epithelial cells upon treatment with these candidates. Proteomic approach in combination with a literature-based pathway analysis showed altered expression of enzymes associated with the regulating integrity of tight junction. The bioehancing potential of these candidates were further validated by using an in vitro model to examine the paracellular transport of a co-incubated therapeutic molecule. The findings of this study could be used as foundational tool for designing a new generation of bioenhancers resulting in higher efficacy of therapeutic molecules.

Committee members: Dr. Shuowei Cai (Advisor) and Dr David Mande from Chemistry & Biochemistry; Dr. Vijaya Chalivendra, Mechanical Engineering; and Dr. Yashwant Pathak, College of Pharmacy, University of South Florida Health.
All BMEBT students are encouraged to attend and all interested parties invited.
Refreshments will be served.

For further information, please contact Dr. Shuowei Cai at 508-999-8807 or by email scai@umassd.edu.