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 glucoseresponsive vesicles (GRVs; with an average diameter of 118 nm), which are loaded with insulin and glucose oxidase (GO x ) 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.diabetes | drug delivery | glucose-responsive | hypoxia-sensitive | microneedle
Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 mM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.
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. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to “closed-loop” insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels. “Closing the loop” between blood glucose level (BGL) measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed.
An enantioselective Overman 3,3-sigmatropic rearrangement
on a quinuclidine skeleton was developed for the pilot-plant synthesis
of a glycine transporter 1 inhibitor. The first stereocenter was produced
by a Ru-catalyzed asymmetric transfer hydrogenation process followed
by chirality transfer using the Overman rearrangement. The second
stereocenter was generated by a diastereoselective hydrogenation reaction.
Bioorganic catalysis is emerging as a powerful tool to complement traditional catalytic reactions in organic synthesis. A wide range of reactions can be catalyzed using biocatalysts, and this article attempts to introduce the reader to the variety of reactions that have been demonstrated. Although these reactions are possible in the laboratory, the challenge is to make them economically feasible on an industrial scale. Each biotransformation process has some unique obstacles to overcome before it is translated from the laboratory to commercial scale, and some of these problems are discussed. Biocatalytic properties are amenable to dramatic modification using genetic and solvent engineering, setting them apart from traditional catalysts. Many biocatalytic processes are being run on a commercial scale and one such reaction utilizing a transaminase is presented as a case study.
Bioorganic catalysis is emerging as a powerful tool to complement traditional catalytic reactions in organic synthesis. A wide range of reactions can be catalyzed using biocatalysts, and this article attempts to introduce the reader to the variety of reactions that have been demonstrated. Although these reactions are possible in the laboratory, the challenge is to make them economically feasible on an industrial scale. Each biotransformation process has some unique obstacles to overcome before it is translated from the laboratory to commercial scale, and some of these problems are discussed. Biocatalytic properties are amenable to dramatic modification using genetic and solvent engineering, setting them apart from traditional catalysts. Many biocatalytic processes are being run on a commercial scale and one such reaction utilizing a transaminase is presented as a case study.
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