Insulin Patch Research Articles

The pectin-insulin patch application prevents the onset of peripheral neuropathy-like symptoms in streptozotocin-induced diabetic rats.

Peripheral neuropathic condition is amongst the classical symptoms of progressed diabetes. An intensive glycemic control with insulin injections has been shown to delay the onset and the progression of this condition in diabetes. In this study, we investigated the effect of pectin-insulin patch application on peripheral neuropathic symptoms in streptozotocin-induced diabetic rats. Pectin-insulin patches (20.0, 40.8, and 82.9 μg/kg) were daily applied thrice in streptozotocin-induced diabetic rats for 45 days. The diabetic animals sham treated with insulin-free patch served as negative control, while diabetic animals receiving subcutaneous insulin served as positive controls. The locomotor activity, gripping strength, and thermal perception were assessed at day 36, day 40, and day 44, respectively. On the 45th day, the animals were sacrificed, after which the plasma insulin, nitric oxide, C-reactive protein, tumor necrosis factor alpha, and malondialdehyde were measured. The patch application attenuated hyperglycemia with an improvement in the locomotor activity, thermal perception, and gripping strength in diabetic animals. Furthermore, the application of the patch augmented plasma nitric oxide while attenuating plasma malondialdehyde and tumor necrosis factor alpha. The application of pectin-insulin patch delays the onset of peripheral neuropathic-like symptoms in diabetic animals.

Core-Shell Microneedle Gel for Self-Regulated Insulin Delivery.

A bioinspired glucose-responsive insulin delivery system for self-regulation of blood glucose levels is desirable for improving health and quality of life outcomes for patients with type 1 and advanced type 2 diabetes. Here we describe a painless core-shell microneedle array patch consisting of degradable cross-linked gel for smart insulin delivery with rapid responsiveness and excellent biocompatibility. This gel-based device can partially dissociate and subsequently release insulin when triggered by hydrogen peroxide (H2O2) generated during the oxidation of glucose by a glucose-specific enzyme covalently attached inside the gel. Importantly, the H2O2-responsive microneedles are coated with a thin-layer embedding H2O2-scavenging enzyme, thus mimicking the complementary function of enzymes in peroxisomes to protect normal tissues from injury caused by oxidative stress. Utilizing a chemically induced type 1 diabetic mouse model, we demonstrated that this smart insulin patch with a bioresponsive core and protective shell could effectively regulate the blood glucose levels within a normal range with improved biocompatibility.

Hypoxia and H2O2 Dual-Sensitive Vesicles for Enhanced Glucose-Responsive Insulin Delivery.

A glucose-responsive closed-loop insulin delivery system mimicking pancreas activity without long-term side effect has the potential to improve diabetic patients' health and quality of life. Here, we developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing insulin-loaded vesicles. Formed by self-assembly of hypoxia and H2O2 dual-sensitive diblock copolymer, the glucose-responsive polymersome-based vesicles (d-GRPs) can disassociate and subsequently release insulin triggered by H2O2 and hypoxia generated during glucose oxidation catalyzed by glucose specific enzyme. Moreover, the d-GRPs were able to eliminate the excess H2O2, which may lead to free radical-induced damage to skin tissue during the long-term usage and reduce the activity of GOx. In vivo experiments indicated that this smart insulin patch could efficiently regulate the blood glucose in the chemically induced type 1 diabetic mice for 10 h.

Development of Miniaturized Nongassing Electroosmotic Pump for the Drug Delivery

Electroosmotic pumps are the simplest among all the pumps, consisting of two electrodes separated by a porous membrane. Most use Pt electrodes and operate at high voltages, electrolyzing water. Because evolved gas bubbles adhere and block parts of the electrodes and the membrane, steady pumping rates are difficult to sustain, and if it pumping in the closed system, the oxygen and hydrogen will mix together and it’s not safe. The use of electrochemical reaction such as Ag/Ag2O to operate the pump non-gassing with higher efficiency. It has simple structure, battery operable, flow rate is linear to voltage and to area of the pump. The pump is now curretly used to develop drug pumps such as insulin patch pump and implantable morphine pump.

Diabetics Say Good Bye to Painful Insulin Injections

A systematic review concluded that inhaled insulin “appears to be as effective, but no better than injected short-acting insulin. But the cost is so much more that it is unlikely to be cost-effective. The inventions did not stop there, following insulin inhalers, the first “smart insulin patch was created by researchers at North Carolina State University and the University of North Carolina at Chapel Hill. Though it has thus far only been tested in a mouse model of type 1 diabetes. According to the paper published in the Proceedings of the National Academy of Sciences. The painless insulin patch has been shown to detect increases in blood sugar levels and secrete doses of insulin into the bloodstream whenever needed. The patch was able to regulate the insulin levels of diabetic mice for nine hours straight.

Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery

A glucose-responsive "closed-loop" insulin delivery system mimicking the function of pancreatic cells has tremendous potential to improve quality of life and health in diabetics. Here, we report a novel glucose-responsive insulin delivery device using a painless microneedle-array patch ("smart insulin patch") containing glucose-responsive vesicles (GRVs; with an average diameter of 118 nm), which are loaded with insulin and glucose oxidase (GOx) enzyme. The GRVs are self-assembled from hypoxia-sensitive hyaluronic acid (HS-HA) conjugated with 2-nitroimidazole (NI), a hydrophobic component that can be converted to hydrophilic 2-aminoimidazoles through bioreduction under hypoxic conditions. The local hypoxic microenvironment caused by the enzymatic oxidation of glucose in the hyperglycemic state promotes the reduction of HS-HA, which rapidly triggers the dissociation of vesicles and subsequent release of insulin. The smart insulin patch effectively regulated the blood glucose in a mouse model of chemically induced type 1 diabetes. The described work is the first demonstration, to our knowledge, of a synthetic glucose-responsive device using a hypoxia trigger for regulation of insulin release. The faster responsiveness of this approach holds promise in avoiding hyperglycemia and hypoglycemia if translated for human therapy.

Smart insulin patch delivers ‘fast, painless, continuous dose’

Smart insulin patch delivers ‘fast, painless, continuous dose’

Advances in pump technology: insulin patch pumps, combined pumps and glucose sensors, and implanted pumps

This review discusses the most recent developments in insulin pump technology. The benefits of the insulin pump to patients with type 1 diabetes are recognized both for its metabolic effectiveness and its positive effects on quality of life. The current pumps are reliable, small and light, and are becoming more and more sophisticated. Nevertheless, there remain practical and psychological constraints for the patient. However, recent patch-pump advances should simplify the technical aspects of pump treatment and enhance patient comfort. Another advance combines the insulin pump with a glucose sensor. Such a combination is logical for optimizing pump use and, to that end, developing an automated or 'closed-loop'system that permits the delivery of subcutaneous insulin adjusted according to measured levels of subcutaneous glucose. Finally, implanted insulin pumps have proven their worth not only because of their simple use, but also for their contribution in the artificial pancreas project. Indeed, the prompt response with intraperitoneal administration of insulin makes it of interest for use in a closed-loop system.

The Novel Insulin Patch Pen Device.

The Novel Insulin Patch Pen Device.

Insulin Patch Pumps: Their Development and Future in Closed-Loop Systems

Steady progress is being made toward the development of a so-called "artificial pancreas," which may ultimately be a fully automated, closed-loop, glucose control system comprising a continuous glucose monitor, an insulin pump, and a controller. The controller will use individualized algorithms to direct delivery of insulin without user input. A major factor propelling artificial pancreas development is the substantial incidence of-and attendant patient, parental, and physician concerns about-hypoglycemia and extreme hyperglycemia associated with current means of insulin delivery for type 1 diabetes mellitus (T1DM). A successful fully automated artificial pancreas would likely reduce the frequency of and anxiety about hypoglycemia and marked hyperglycemia. Patch-pump systems ("patch pumps") are likely to be used increasingly in the control of T1DM and may be incorporated into the artificial pancreas systems of tomorrow. Patch pumps are free of tubing, small, lightweight, and unobtrusive. This article describes features of patch pumps that have been approved for U.S. marketing or are under development. Included in the review is an introduction to control algorithms driving insulin delivery, particularly the two major types: proportional integrative derivative and model predictive control. The use of advanced algorithms in the clinical development of closed-loop systems is reviewed along with projected next steps in artificial pancreas development.

Aspects of Insulin Treatment

This is the second of a series of articles based on presentations at the American Diabetes Association Scientific Sessions held 5–9 June 2009 in New Orleans, Louisiana, pertaining to insulin treatment approaches. At a symposium on aspects of continuous subcutaneous insulin infusion (CSII) treatment, Nancy Bohanon (San Francisco, CA) discussed new approaches to make this treatment available for subjects with type 2 diabetes and pointed out that “the pumps work!” She predicted that several of these products might be available within the next year. ### Patch pumps The Valeritas h-Patch technology has been used to develop a V-Go insulin patch pump (www.valeritas.com) to deliver both basal and bolus insulin, requiring a fixed basal dose, which appears to be preset to rates of 20, 30, and 40 units per 24 h. For bolus delivery, each click delivers 2 units up to a total of 36 units per 24 h. The pump is worn for 24 h, filled with an external device, with the backing removed to adhere to the skin. A button on the pump is pressed to insert a 30G needle. Bolus doses are delivered by pressing a button on one side that releases a bolus delivery deployment button—a safety feature to prevent accidental bolus delivery. After 24 h, a button is pressed to withdraw the needle. The device is purely mechanical, does not require a battery-driven pump or external controller, fits under clothing, and can be operated through clothing. In a user-preference program, patients liked it and considered it to be easy to use, discrete, and comfortable, although the filling mechanism was not considered to be ideal. Common to a number of these devices, although presumably allowing a less complex delivery mechanism, the single preset basal rate is somewhat disadvantageous, as an important benefit of CSII basal rates is the ability to …

Transdermal delivery of insulin from a novel biphasic lipid system in diabetic rats.

Noninvasive transdermal insulin delivery could provide diabetic patients with sustained physiological levels of basal insulin in a pain-free manner. We have developed a novel transdermal lipid-based system (Biphasix) suitable for macromolecule delivery across the skin. The objective of this study was to evaluate the pharmacological effects of the Biphasix-insulin delivery system in a diabetic rat model. Transdermal patches (one per animal) containing Biphasix-insulin formulation (10 mg of recombinant human insulin dose) were applied to the shaved abdominal skin of streptozotocin-induced diabetic rats for 48 h. Blood glucose was monitored every 2-4 h using a Lifescan glucose meter. Serum insulin levels were analysed by enzyme-linked immunosorbent assay. A decrease in blood glucose of 43.7 +/- 3.8% (mean +/- SEM, n = 25) was observed compared with initial blood glucose levels. The duration of the response was 51.5 +/- 3.7 h (mean +/- SEM, n = 25). Serum insulin after application of the transdermal Biphasix-insulin patch was 20.08 +/- 5.44 micro IU/mL (mean +/- SEM, n = 13) during the steady state, which was not statistically different from the insulin levels obtained 2 h after subcutaneous injection of 1 mg of recombinant human insulin solution. Insulin bioavailability from the transdermal Biphasix-insulin patches was 21.5 +/- 6.9% (mean +/- SEM, n = 13) based on serum insulin and 39.5 +/- 8.5% (mean +/- SEM, n = 25) based on the pharmacodynamic blood glucose-lowering effects. The Biphasix system successfully delivered insulin transdermally, as evidenced by a significant sustained decrease in blood glucose in diabetic rats, with a corresponding increase in serum insulin. These results support the feasibility of developing a transdermal insulin patch for human applications.