Dipti Deshpande Receives the American Association of Indian Pharmaceutical Scientists (AAiPS) 2012 Student Scholar’s Award
Dipti Deshpande, a doctoral candidate currently pursuing her PhD in the Department of Pharmaceutical Sciences, School of Pharmacy at the Northeastern University was awarded the “AAiPS 2012 Student Scholar’s Award” at the 2012 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition at McCormick Place in Chicago, IL. She is currently working in Distinguished Professor and Chairman, Dr Mansoor Amiji’s laboratory and her thesis is titled, “Multimodal Omega-3 Fatty Acid Oil-Containing Nanoemulsion-Based Therapeutic Strategy for the Treatment of Endothelial Dysfunction in Coronary Artery Disease”.
Cardiovascular diseases are the leading cause of mortality in US and most countries worldwide. Coronary artery disease, mainly atherosclerosis has been identified as the primary predisposing factor that contributes towards the onset of these diseased conditions. The main goal of this project is to evaluate the benefits of 17-β-Estradiol (17-βE) loaded omega-3-fatty acid oil containing nanoemulsion system in the treatment of atherosclerosis. Since the development and progression of atherosclerosis involves a complex interplay between inflammation, hyperlipidemia, oxidative damage and endothelial dysfunction; the primary aim of developing this system is to target the disease in a multimodal fashion. While cardioprotective effects of 17-βE and omega-3-fatty acids are well known, the novelty of this system lies in combining these two molecules for enhanced delivery of these agents along the damaged arterial vessels. Since 17-βE is a natural hormone and flax seed oil belongs to the GRAS (generally regarded as safe) grade of chemicals, this nanoemulsion system has minimal toxicity and has been designed for longer circulation through incorporation of polyethylene glycol (PEG) in the system.
Preliminary studies have successfully demonstrated efficient loading and stability of the 17-βE loaded nanoemulsion system. Cell trafficking studies further showed effective intracellular uptake and internalization in the cultured aortic vascular cells. In addition, the system shows several benefits through modulation of the various overlapping pathways that are involved in cases of arterial disorders. This includes cell-specific modulation of the cellular MAPK activity, inhibition of vascular inflammation and up-regulation of the vascular nitric oxide tone in cultured aortic vascular cells. Thus, the future studies are focused on evaluating the benefits of the 17-βE loaded nanoemulsion system in vivo in a high-fat diet induced model of atherosclerosis using the ApoE-/- mice. The ongoing studies will evaluate the distribution and tissue retention of 17-βE in the mice when delivered using the nanoemulsion system. The studies will also look at the safety and efficacy of this system in the treatment of atherosclerosis in these animals especially by evaluating the lipid profile, inflammatory markers and atherosclerotic lesions observed in the diseased animals. The results from this study can help develop a non-invasive drug delivery approach for the treatment of atherosclerosis that can at least partially circumvent the problems associated with the current invasive treatment approaches like stents and balloon angioplasty.