Daily injections for basal insulin therapy are far from ideal resulting in hypo/hyperglycemic episodes associated with fatal complications in type-1 diabetes patients. The purpose of this study was to develop a thermosensitive copolymer-based in situ depot forming delivery system to provide controlled release of insulin for extended duration following a single subcutaneous injection, closely mimicking physiological basal insulin requirement. Size and nature of the incorporated therapeutic were observed to affect the release profile of insulin. Modification with zinc and chitosan preserved thermal, conformational, and chemical stability of insulin during the entire duration of storage (up to 9 months at 4 °C) and release (up to 3 months at 37 °C). In vivo, daily administration of long-acting insulin, glargine, resulted in fluctuating blood glucose levels between 91 – 443 mg/dL in type 1 diabetic rats. However, single administration of oleic acid-grafted-chitosan-zinc-insulin complexes incorporated in copolymer formulation demonstrated slow diffusion of insulin complexes maintaining peak-free basal insulin level of 21 mU/L for 91 days. Sustained release of basal insulin also correlated with efficient glycemic control (blood glucose <120 mg/dL), prevention of diabetic ketoacidosis and absence of cataract development, unlike other treatment groups. The suggested controlled basal insulin delivery system has the potential to significantly improve patient compliance by improving glycemic control and eliminating life-threatening diabetes complications. Furthermore, oleic acid-grafted-chitosan (CO) nanomicelles were investigated as a non-viral vector to deliver plasmid DNA encoding short hairpin RNA (shRNA) against pro-inflammatory cytokines to adipose tissue macrophages and adipocytes for the treatment of insulin resistance. Nanomicelles modified using mannose (COM) and adipose homing peptide (AHP) (COA) showed significantly higher uptake and transfection efficiency in inflamed macrophages- adipocytes co culture owing to glucose transporter-1 and prohibitin receptor mediated internalization, respectively. Ligand modified nanomicelles loaded with shRNA against tumor necrosis factor alpha (COM-TNFα) and monocyte chemoattractant protein-1 (COA-MCP1) demonstrated significant attenuation of pro-inflammatory cytokines and improved insulin sensitivity and glucose tolerance in obese-diabetic mice for six weeks post treatment with single dose of optimized formulation. Overall, chitosan nanomicelles mediated targeted gene therapy can help attenuate inflammation, the chief underlying cause of insulin resistance, thereby helping reverse the progression of diabetes. / National Institutes of Health (NIH) grant R15GM114701 / ND EPSCoR seed award FAR0030636

Blood glucose management in Type 1 diabetes is crucial in preventing several diabetic complications. Blood glucose management is a complex task requiring diabetics too carefully administer the correct dosages of insulin by taking their blood glucose levels, food consumption, exercise, stress, illnesses and several other factors into account. Improved bolus calculation greatly aids in controlling blood glucose levels within a tight range. This study investigates how the ets-concept (Equivalent Teaspoons Sugar-concept) can be used to develop products to calculate insulin boluses. A cellular phone based software application was developed to calculate insulin boluses using the ets-concept. This product was tested in a clinical trial. A blood glucose characterization procedure was also developed to characterize the blood glucose response of a Type 1 diabetic to carbohydrate ingestion and insulin administration. The characterization procedure was used during the clinical trial to characterize patients in order to customize the bolus calculation products for the specific diabetic user. / Thesis (Ph.D. (Mechanical Engineering)--North-West University, Potchefstroom Campus, 2006

The correct administration of insulin is a constant challenge for type 1 diabetics. The correct insulin regime leads to fewer complications and an easier way of life. The amount of insulin administered must take into account the meals eaten, previous administered insulin, exercise etc. A rapid process for determining insulin regimes that is accessible to type 1 diabetics will greatly reduce diabetic complications later in life. This study researches such a process. Software is developed to use the ets-concept to simulate blood glucose levels. From these simulations blood glucose characterisation can be done to propose insulin regimes. Data gathered in previous studies is used to verify the results of this process. These results are compared to factors that describe the accuracy of a person's blood glucose control. The effects the new regimes will have are used to make recommendations to the end-user. Accurate characterisation leads to insulin regImes that will Improve the control performance of type 1 diabetes. / Thesis (M.Ing. (Electronical Engineering)--North-West University, Potchefstroom Campus, 2008.

Blood glucose management in Type 1 diabetes is crucial in preventing several diabetic complications. Blood glucose management is a complex task requiring diabetics too carefully administer the correct dosages of insulin by taking their blood glucose levels, food consumption, exercise, stress, illnesses and several other factors into account. Improved bolus calculation greatly aids in controlling blood glucose levels within a tight range. This study investigates how the ets-concept (Equivalent Teaspoons Sugar-concept) can be used to develop products to calculate insulin boluses. A cellular phone based software application was developed to calculate insulin boluses using the ets-concept. This product was tested in a clinical trial. A blood glucose characterization procedure was also developed to characterize the blood glucose response of a Type 1 diabetic to carbohydrate ingestion and insulin administration. The characterization procedure was used during the clinical trial to characterize patients in order to customize the bolus calculation products for the specific diabetic user. / Thesis (Ph.D. (Mechanical Engineering)--North-West University, Potchefstroom Campus, 2006

The correct administration of insulin is a constant challenge for type 1 diabetics. The correct insulin regime leads to fewer complications and an easier way of life. The amount of insulin administered must take into account the meals eaten, previous administered insulin, exercise etc. A rapid process for determining insulin regimes that is accessible to type 1 diabetics will greatly reduce diabetic complications later in life. This study researches such a process. Software is developed to use the ets-concept to simulate blood glucose levels. From these simulations blood glucose characterisation can be done to propose insulin regimes. Data gathered in previous studies is used to verify the results of this process. These results are compared to factors that describe the accuracy of a person's blood glucose control. The effects the new regimes will have are used to make recommendations to the end-user. Accurate characterisation leads to insulin regImes that will Improve the control performance of type 1 diabetes. / Thesis (M.Ing. (Electronical Engineering)--North-West University, Potchefstroom Campus, 2008.

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