Browsing by Subject "Type I diabetes"
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Item Intelligent delivery via enzyme active hydrogels(2009-12) Marek, Stephen Richard; Peppas, Nicholas A., 1948-Advances in medical treatment are leading away from generalized care towards intelligent systems or devices which can sense and respond to their environment. With these devices, the burden of monitoring and dosing for treatment can be removed from the doctor (or the patient) and be placed on the device itself. Implicit closed-loop control systems will allow the device to respond to its environment and release therapeutic agent in response to a specific stimulus. Environmentally responsive hydrogels show great promise in being incorporated in such an intelligent device, such as pH-responsive hydrogels which can swell and deswell in response to changes in the pH of the media. Thus, pH changes can be exploited for controlled and intelligent drug delivery when used in combination with these pH-responsive hydrogels. In this work, heterogeneous, thermal-redox initiated free-radical polymerizations were developed to synthesize novel pH-responsive hydrogels, microparticles, and nanogels. The specific disease of interest was type I diabetes, which requires daily doses of insulin both at a basal amount and either a postprandial or preprandial bolus in order to maintain blood glucose levels within safe limits. To allow pH-responsive hydrogels to be sensitive to glucose, glucose oxidase was incorporated which oxidizes glucose to gluconic acid. A novel inverse-emulsion polymerization method was developed for the synthesis of poly[2-(diethylaminoethyl methacrylate)-grafted-polyethylene glycol monoethyl ether monomethacrylate] (P(DEAEM-g-PEGMMA)) nanogels (100-400 nm) for intelligent insulin delivery. The new polymerization method allowed the incorporation of hydrophilic components, such as glucose oxidase and catalase, as well as PEG surface tethers of lengths 400 Da up to 2000 Da. Surface tethers successfully decreased the surface charge of the nanogels. Insulin loading and release was determined for microparticles which were able to imbibe substantial amounts of insulin from solution when swollen, entrap the insulin when collapsed, and then release the insulin in response to either a pH or glucose stimulus.Item Regulation of calcium stores in normal and diabetic endothelial cells(Texas Tech University, 2000-12) Sanka, Shankar ChittaranjanCytosolic Ca^^ ([Ca^^]*'^^) mediates many cellular ftinctions, e.g.. cell growth, motility, secretion, etc. In many cell types, ion transport processes appear to be dependent on metabolism of glucose for maximal activity. In certain cell types, a strict coupling between glycolysis and the acfivity of Endoplasmic Reticulum Ca^"-ATPases (SERCA). involved in regulating Ca^^ homeostasis, has been suggested. In diabetes, glucose homeostasis is altered. We hypothesize that Ca^^ homeostasis in microvascular endothelial cells from diabetic animals is altered due to a dysfunction of glycolysis coupling the activity of SERCA. We further hypothesize that endosomal/lysosomal (E/L) compartments exhibiting SERCA are involved in this dysfunction. Our data indicated that agonist stimulation (ATP, vasopressin, angiotensin-II)elicited [Ca^"]^^* increases (independent of extracellular Ca^^) that were larger in endothelial cells from diabetic than from normal animals. Simultaneous measurements of [Ca^^]'^^' and Ca^^ in E/L compartments ([Ca^^]^) using fluorescence spectroscopy, indicated that E/L compartments released Ca^^ following agonist-stimulation. The magnitude of the Ca'* release was significantly larger in microvascular endothelial cells from diabetic rats. SERCA inhibitors elicited Ca^^ releases from E/L compartments in both normal and diabetic models. The magnitude of the [Ca^^]^ release was however similar among normal and diabetic cells. Immunocytochemical experiments demonstrated that 60% of E/L compartments exhibited SERCA. These data indicate that (a) E/L compartments are important for Ca^^ homeostasis in microvascular endothelial cells from both normal and diabetic models; (b) Ca^^ regulation in E/L compartments is different in cells from a diabefic model, (c) the compartment involved in altered Ca'* homeostasis in diabetes is unknown.