Nanotechnology and Nanomedicine in Diabetes

For Instructors Request Inspection Copy. Understanding the importance of nanosciences in diabetes is problematic as some texts can be too technical for the novice. This book uses a reader—friendly format suitable not only for practitioners but newcomers as well. It begins with general aspects of nanotechnology and nanomedicine in diabetes. It then discusses glucose and glucose sensors based on functional nanocomposites before moving on to a discussion of insulin and the use of nanoprobes to monitor cell processes in the pancreas.

Finally, it explores drugs and other treatments, including second-generation sulfonylurea glipizide loaded biodegradable nanoparticles and nanoparticle-mediated delivery of angiogenic inhibitors in diabetic retinopathy. General Aspects Nanotechnology and Nanomedicine in Diabetes: An Overview, Denison J. Fangueiro, and Selma S. Souto Atomic Force Microscopy: Rodriguez and Suzanne P. Sajeesh , Chandra P.

Visit our Beautiful Books page and find lovely books for kids, photography lovers and more. An Overview, Denison J. Fangueiro, and Selma S. Souto Atomic Force Microscopy: Rodriguez and Suzanne P. Sajeesh , Chandra P. Bonn, and Christian W. These matrices can reversibly swell when PBA forms a boronate ester with glucose. The ester formation leads to an accumulation of negative charge on the matrix, which results in repulsive forces that cause the cross-linked matrix to swell and release insulin. The micelle was capable of swelling in response to glucose concentration. The core of the micelle shifted from being hydrophobic to hydrophilic as the glucose formed a complex with the PBA moiety in the core of the micelle.

The insulin stored within the micelle was then released in glucose dependent manner. In the absence of glucose the micelle was stable and no insulin release was detected. One of the primary issues with using PBA in clinical systems is that the tetrahedral form requires a pH higher than those observed in most physiological systems. Yao and co-workers developed a polymeric glucose-responsive insulin delivery system that operates under neutral pH conditions Electron donating groups were included within the polymer to increase its Lewis acidity and thereby reduce the pKa required to form the boronate ester.

The system was stable at normal blood sugar levels, and this stability reduced the risk of a burst release of insulin, which is highly desirable in a self-regulating insulin delivery device. Polymer based insulin delivery systems have great versatility. Modifying the structure of the polymer can be used to tune the insulin release behaviour and sensitivity.

Kim and co-workers synthesized a PEG-polyboroxole block co-polymer polymersome which was capable of self-assembly into micelles or cylindrical polymersomes based on the polyboroxole block length The group reported that at neutral pH, binding of the boroxole group to monosaccharides such as glucose 0. The polymersomes did not dissolve in the absence of monosaccharaides, and instead maintained their morphology for up to 3 months.

The boroxole group showed a stronger binding affinity for fructose over glucose, but the versatility this system shows promise for self-regulated insulin delivery platforms. Several groups have attempted to create platforms which exhibit a step wise response to glucose concentration and can deliver multiple drugs. Zhao and co-workers used Mesoporous Silica Nanoparticles MSNs as a platform for glucose-responsive release of Insulin and cyclic adenosine monophosphate cAMP — a trigger for the production of insulin from pancreatic beta cells Furthermore, MSNs have been shown to be internalized by cells through endocytosis; this facilitates the uptake of cAMP, which normally encounters difficulty in crossing the cell membrane.

The system was well realized and showed almost no leaching of cAMP without a glucose or fructose trigger. An ideal payload of insulin to lower blood glucose is about — pM The prospect of a dual delivery system is an exciting one, and has led to an increase in interest in MSNs for insulin delivery 37 , 52 , 66 , However, the modification of insulin with gluconic acid raises questions about the bioavailability of the drug once released from the MSN.

Wu and coworkers designed a multifunctional hybrid nanogel system to serve as an insulin delivery device and glucose sensor Figure 8 10 , The polymer is capable of crosslinking to form a nanogel which undergoes a phase transition in response to glucose concentration. The group included silver nanoparticles in the core of the nanogel that endows it with strong fluorescence.

The wavelength of this flourescence changes as the nanogel swells and shrinks in proportion to glucose concentration. In addition to the sensing mechanism, the system is also capable of dispensing insulin in a glucose-responsive fashion by swelling in response to hyperglycaemic conditions.

The system was capable of phase transitions at a physiologically relevant pH 7. Insulin release at basal levels could be sustained for over 2 days. Glucose-responsive insulin delivery systems utilizing phenylboronic acid. A Insulin release via pH responsive micelles. B Multifunctional hydrogel for glucose-responsive insulin release and glucose concentration measurement.

As the smart hydrogel swells in response to hyperglycemic conditions, the insulin is released and the fluorescence of the silver nanoparticles AgNPs is modulated.

This fluorescence change can be detected and used to quantify the glucose concentration and the release of insulin. Significant advances in both glucose sensors and self-regulated insulin delivery systems have been facilitated by nanotechnology. Amperometric sensors utilizing nanotechnology now facilitate rapid, accurate, and highly sensitive glucose measurements in blood and other clinically relevant fluids, such as tears and urine. Additionally, recent advances in fluorescent glucose detection holds the potential to lead to continuous in vivo glucose measurement.

The realization of sensors which do not require repeated finger pricks to draw blood for glucose testing is highly desirable, as alternatives which avoid the pain, tissue damage, and patient noncompliance associated with the legacy clinical standard are highly desirable 5. Furthermore, the clinical realization of a continuous glucose sensor could lead to closed-loop systems which could utilize existing insulin pumps 6. This could relieve the patient of the significant burden of continuously managing their diabetes, and may tremendously improve their long term health outcomes and well-being.

Based on current developments in nanoscale glucose sensing, we can expect great clinical applications of this technology in the near future Progress in closed-loop insulin delivery systems has been encouraging and shows tremendous promise for the treatment of diabetes. Current closed-loop systems are capable of releasing large amounts of insulin; however, clinical realization requires tight control of insulin release to reduce the risk of insulin overdose.

Glucagon, a hormone which works antagonistically with insulin, could be co-delivered to reduce the risk of hypoglycaemia 3. Additionally, because insulin is a growth factor, long term exposure to excess insulin can cause changes to the cell division process Systems that offer remote control for the release of insulin are a promising development in dynamic insulin delivery.

Stanley and co-workers developed nanoparticles coated with antibodies capable of binding to TRPV1 calcium channels on genetically engineered cells. The application of a kHz RF signal causes localized heating of the channel via heating of the nanoparticles, and this heating causes subsequent passage of calcium into the cell, triggering the production of insulin within the cell The cells then release this insulin into the bloodstream Additionally, Di, et al.

A nano-network 48 comprised of PLGA nanoparticles containing insulin was used to form an insulin reservoir, which could be selectively degraded by the application of focused ultrasound and lead to insulin release in response to ultrasound application These remotely triggered strategies may lead to novel insulin delivery modalities which can reduce the pain associated with repeatedly injecting insulin and increase patient compliance, 5 and may serve as an element of closed-loop glucose therapies.

The best way of tackling the challenges ahead is by taking a multidisciplinary approach and incorporating knowledge of material science, physical chemistry, and pharmacology to develop more nuanced systems that are dynamic and stable. In this study, Yum, et al used fluorescent carbon nanotubes with boronic acid to fabricate an optical glucose sensor.

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As the boronic acid binds to the nanotubes, the fluorescence is quenched. As glucose binds to these boronic acids, the fluorescence returns. The authors declare no conflicts of interest. National Center for Biotechnology Information , U. Wiley Interdiscip Rev Nanomed Nanobiotechnol. Author manuscript; available in PMC Jul 1. Author information Copyright and License information Disclaimer. The publisher's final edited version of this article is available at Wiley Interdiscip Rev Nanomed Nanobiotechnol.

See other articles in PMC that cite the published article. Abstract Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics.

Introduction Diabetes is a metabolic disease characterized by chronically elevated blood glucose levels BGLs and an inability to maintain BGL homeostasis 1 , 2. Open in a separate window. Schematic of research themes using nanotechnology for diabetes treatment. Nanotechnology Enabled Glucose Sensing Accurate and frequent glucose measurements are the basis of contemporary diabetes management. Table 1 Summary of reported glucose measurement systems. Electrochemical Glucose Measurement The excellent conductivity and catalytic ability of nanoscale carbon structures has led to their use in a variety of glucose sensing modalities 23 — Optical Glucose Measurements Optical glucose measurements typically involve an increase in fluorescence intensity or a shift in the wavelength of the light produced by a fluorescent material coupled with a glucose sensitive material.

Glucose-Responsive Insulin Delivery Synthetic closed-loop systems are often characterized by their method of glucose detection. Glucose Oxidase GOx Systems Glucose oxidase is capable of enzymatically catalysing the oxidation of glucose to gluconic acid with high specificity. Phenylboronic Acid PBA Systems A disadvantage of protein based glucose sensing is that environmental factors such as pH and temperature must be tightly controlled to prevent protein denaturation.

Conclusion and Outlook Significant advances in both glucose sensors and self-regulated insulin delivery systems have been facilitated by nanotechnology. Footnotes The authors declare no conflicts of interest. Prausnitz MR, Langer R. Diagnosis and Classification of Diabetes Mellitus.

Chemistry and Biochemistry of Type 2 Diabetes. Diabetes and cardiovascular disease. Emerging micro- and nanotechnology based synthetic approaches for insulin delivery. Materials for diabetes therapeutics. Nanomedicine and its potential in diabetes research and practice. A glucose sensor protein for continuous glucose monitoring. Chemically controlled closed-loop insulin delivery.

Journal of Controlled Release. Drug Delivery Interfaces in the 21st Century: Fluorescence lifetime imaging microscopy of intracellular glucose dynamics. Journal of Diabetes Science and Technology. Electrodeposition of chitosan—ionic liquid—glucose oxidase biocomposite onto nano-gold electrode for amperometric glucose sensing.

Organization of glucose-responsive systems and their properties. Enhanced amperometric detection of glucose using Si29 particles. Near-infrared optical sensors based on single-walled carbon nanotubes. Amplifying a Nanoscale Actuator. Electrospun Co3O4 nanofibers for sensitive and selective glucose detection. Continuous analyte sensing with magnetic nanoswitches. Concanavalin A for in vivo glucose sensing: Modeling of spherical fluorescent glucose microsensor systems: New England Journal of Medicine.

Ultrathin polymeric coatings based on hydrogen-bonded polyphenol for protection of pancreatic islet cells. Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug. Behavior of synthetic polymers immobilized on a cell membrane. Journal of the American Chemical Society. Bioorthogonal layer-by-layer encapsulation of pancreatic islets via hyperbranched polymers.

Multiple functionalities of polyelectrolyte multilayer films: A glucose-responsive controlled release system using glucose oxidase-gated mesoporous silica nanocontainers.

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Oral glucose-and pH-sensitive nanocarriers for simulating insulin release in vivo. Applications of advanced hybrid organic—inorganic nanomaterials: Signalling through C-type lectin receptors: Glucose- and pH-responsive controlled release of cargo from protein-gated carbohydrate-functionalized mesoporous silica nanocontainers. Polyol Complexes and Structure of the Benzeneboronate Ion. The Journal of Organic Chemistry.