Day 1 :
Baylor University Medical Center, USA
Time : 09:40-:10:20
Bashoo Naziruddin has been the Director of the cGMP Islet Cell Processing Laboratory at Baylor University Medical Center since April 2003. He is also an Adjunct Associate Professor at the Institute of Biomedical Studies at Baylor University, Waco, Texas. His current research is focused on “Immunobiology of human islet cell transplantation”. His specific research topics include assessment of immune response in islet transplant recipients, development of an optimal immunosuppressive regimen for islet transplantation, strategies to induce tolerance towards donor islets, identification of novel drugs to prevent islet rejection, and potential use of islets from pigs for transplantation into humans. He has published more than 113 research articles in peer-reviewed journals and has co-authored chapters in two books on Organ Transplantation and Type 1 Diabetes. He has also given more than 126 presentations at international/national scientific meetings and has delivered invited talks at reputed institutions.
Transplantation of islets isolated from deceased donor pancreas (ITA) is a promising minimally invasive treatment for patients suffering from severe form of type 1 diabetes to attain normoglycemia. Although this treatment was conceptualized more than a century ago, its application in clinical practice has seen a remarkable increase only from the year 2000. It is the only procedure known to provide a “transient cure” for type 1 diabetic patients in terms of their dependence on exogenous insulin use. Despite offering several advantages as a treatment for autoimmune diabetes, ITA is also facing several hurdles in its broader implementation. The quality of donor pancreas, islet isolation methodology, islet engraftment and immunosuppression play major role in the success of clinical islet transplants. A unique innate immune response against intraportally transplanted islets called instant blood-mediated inflammatory reaction causes significant destruction (~50% of transplanted islet mass) affecting the islet engraftment. According to the recent report by the collaborative islet transplant registry, 864 type 1 diabetic patients have received 1679 islet transplants. It is common for one patient to receive more than one islet transplant to achieve an optimal islet dose. The clinical outcomes have demonstrated that ITA is highly efficient in the prevention of severe hypoglycemic events. In terms of attainment of insulin independence, ITA has shown remarkable progress in recent years with ~50% of the recipients retaining the insulin independent status at 5 years post-transplant. Introduction of polyclonal T cell depleting antibodies and anti-inflammatory drugs during induction period were the major reasons for the improvement in islet graft function. A recently completed phase III clinical trial has confirmed the safety and efficacy of ITA. Our team has introduced a combination of Etanercept and Anakinra, which block TNF-a and IL-1b respectively, in a cohort of islet transplant patients and have shown improved islet graft function. Effective control of alloimmune and autoimmune responses may significantly improve the islet graft function. Increased clinical application of ITA is also awaiting approval of biological license application by the Food and Drug Administration.
University of Florida, USA
Time : 10:20-11:00
Anil K Mandal is board certified in Internal Medicine and Nephrology (not yet recertified in Nephrology). Diabetes Mellitus is the most common cause of kidney failure in the USA and worldwide; this strong association between diabetes and kidney failure has inspired him to develop the framework of Mandal Diabetes Research Foundation to assist diabetic patients in living a good life with medical treatment, and avoiding dialysis. He is a published author/editor of 12 books and more than 100 articles on research in diabetes and kidney disease. He is a two-time Fulbright Scholar and a Visiting Professor of 23 countries which permitted lectures on diabetes, high blood pressure and kidney diseases on five continents of the world. His astute knowledge and total dedication help patients get better and to live a good life.
We previously reported that dglucose is a strong predictor of renal function change in diabetes. This study is an expansion of a previous study with longer duration. Data was compared between first and last visits. Eighty five diabetic patients were treated with a combination of glargine or detemir and regular or fast acting insulin for 26.3+24.6 (SD) months. Blood pressure was controlled by beta blockers, calcium channel blockers, sympathetic inhibitors, or a combination, and chlorthalidone in resistant cases. Angiotensin converting enzyme inhibitors and receptors blockers (ACEI/ARB) were excluded in order to reduce the risk of acute and chronic renal failure. Objectives were to determine if this paradigm of treatment prevents progression of diabetic nephropathy. Fasting (F) and 2-hour postprandial (2hPP), glucose, serum creatinine (scr) and estimated glomerular filtration rate (eGFR); haemoglobin A1 c (HbA1 c); and sitting systolic and diastolic blood pressure (SBP, DBP) were recorded for first and last visits. Mean blood pressure (MBP) and differences (d, 2hPP-F) were calculated for glucose, scr, and eGFR. Parameters between first and last visits were compared using a paired t-test adjusted for age, gender and duration of treatment with P<0.05 considered significant. Significant differences were found between first and last visits for F and 2hPP glucose, F and 2hPP scr, and F and 2hPP eGFR, and HbAl c. dglucose, sitting SBP and MBP were significantly lower at last compared to first visit. Combining both visits dglucose and HbAl c showed a direct and positive correlation with dscr. Change in post minus pre-treatment values was significantly positive and correlated between HbAl c and FBG, 2hPPG or dglucose. In conclusion the current study emphasizes the importance of control of dglucose (2hPP-F) with insulin in preserving renal function in diabetes.
Roquette America Inc., USA
Keynote: How, why and when modified beta cyclodextrins are effective solubilizing tools for parenterals?
Time : 12:00-12:40
Carmen Popescu obtained her BS degree in Physics and PhD in Biophysics at University of Bucharest, Romania. She is a Senior Project Coordinator at Roquette America Inc. and Adjunct Associate Professor with University of Illinois at Chicago, Roosevelt University, University of Tennessee and University of Maryland. She has published over 120 research papers, book chapters and presentations on classic and new drug delivery dosage forms for small and large molecules. Additionally she is a reviewer for the International Journal of Pharmaceutics, Journal of Pharmaceutical Sciences, European Journal of Pharmaceutics and Biopharmaceutics, Journal of Pharma & Pharmaceutical Science and an active member of AAPS and CRS.
In finding new APIs combinatorial and high throughput chemistry strategies favor leads with hydrophobicity-driven potency properties. API high specificity and potency translates in high cLog P, high molecular weight, high melting point and very low solubility. Formulation scientists have reported myriad of conventional and advanced formulation strategies to improve solubility. However, many of them are still at bench stage because industrial scale equipment is not yet available and is financially difficult to be sustained. In recent years formulator’s attention was focusing on cyclodextrins as a solubilizing tool for their stubborn, like bricks, APIs. The reason is obvious: easy to scale up and a successful presence of parenterals as commercially available brands. This presentation is centered on a coherent approach of insoluble APIs solubilization by modified beta cyclodextrin complexation in liquid phase as well as solid dispersions (spray drying, lyophilization) through an extensive array of case studies (carbamazepine, danazol, albendazole, furosemide, zotepine, zaleplon, lorazepam, progesterone, celecoxib, furosemide, valsartan and NSAIDs (flurbiprofen, ibuprofen, ketoprofen, naproxen, piroxicam). If your API contains more than 5 atoms (C, P, S, and N) to form the skeleton of the drug molecule, less than 5 rings, water solubility is less than 10mg/ml, melting point temperature is below 250°C, the molecular weight between 100 and 400 and has stability issues (chemical, photo, etc.) then it is the best candidate for solubilization by cyclodextrin complexation. If API has good performance does not requires solubilization optimization and you are still wondering “why cyclodextrin complexation? “one should not forget that they can offer increased stability (physical, chemical), new formulation, patent extension, increased shelf life, etc.