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The treatment of diabetes lies in developing novel functional carriers, which are expected to have the unique capability of monitoring blood glucose levels continuously and dispensing insulin correctly and timely. Hence, this study is proposing to create a smart self-regulated insulin delivery system according to changes in glucose concentration. Temperature and glucose dual responsive copolymer microcapsules bearing N -isopropylacrylamide and 3-acrylamidophenylboronic acid as main components were developed by bottom-spray coating technology and template method. The insulinoma β-TC6 cells were trapped in the copolymer microcapsules by use of temperature sensitivity, and then growth, proliferation, and glucose-responsive insulin secretion of microencapsulated cells were successively monitored. The copolymer microcapsules showed favorable structural stability and good biocompatibility against β-TC6 cells. Compared with free cells, the biomicrocapsules presented a more effective and safer glucose-dependent insulin release behavior. The bioactivity of secreted and released insulin did not differ between free and encapsulated β-TC6 cells. The results demonstrated that the copolymer microcapsules had a positive effect on real-time sensing of glucose and precise controlled release of insulin. The intelligent drug delivery system is supposed to mimic insulin secretion in a physiological manner, and further provide new perspectives and technical support for the development of artificial pancreas.

The dose response of postprandial plasma glucose (PPG) to add-on, premeal oral hepatic-directed vesicle-insulin (HDV-I), an investigational lipid bio-nanoparticle hepatocyte-targeted insulin delivery system, was evaluated in a 3-test-meal/day model in type 2 diabetes patients. The single-blind, placebo-controlled, dose-escalating trial enrolled 6 patients with HbA(1c) 8.6 ± 2.0% (70.0 ± 21.9 mmol/mol) and on stable metformin therapy. Patients received oral HDV-I capsules daily 30 minutes before breakfast, lunch, and dinner as follows: placebo capsules, 0.05, 0.1, 0.2, and 0.4 U/kg on days 1, 2, 3, 4, and 5, respectively. Outcome measures were PPG and incremental PPG area under the concentration-time curve (AUC). All 4 doses of oral HDV-I statistically significantly lowered mean PPG (P ≤ .0110 each) and incremental PPG (P ≤ .0352 each) AUC compared to placebo. A linear dose response was not observed. The 0.05 U/kg dose was the minimum effective dose in the dosage range studied. Three adverse events unrelated to treatment were observed. Add-on oral HDV-I 0.05-0.4 U/kg significantly lowered PPG excursions and the dose response curve was flat. These results are consistent with the lack of a linear dose response between portal and systemic plasma insulin concentrations in previous animal and human studies. Oral HDV-I was safe and well tolerated., (© 2014 Diabetes Technology Society.)

Insulin-loaded nanofibers were prepared using chitosan as a natural polymer. The loaded insulin with polyethylene oxide was used for preparing monolayer batch S1. Nanofiber S1 was coated by seven layers of film on both sides to form batch S2 as a sandwich containing Layer A (CS, PEG and PEO) and Layer B (PEG and PEO) using electrospinning apparatus. SEM, TEM and FT-IR techniques were used to confirm the drug loading within the composite nanofibers. The in vitro activity that provided a sustained and controlled release of the drug from the nanofiber batch was studied at different pH values spectrophotometrically using a dialysis method. In batches S1 and S2, the release of insulin from nanofiber proceeds via burst release necessary to produce the desired therapeutic activity, followed by slow step. The rate and the percentage release of insulin in batch S2 are found to be higher at all pH values. [ABSTRACT FROM AUTHOR]

An adaptive-learning model predictive control (AL-MPC) framework is proposed for incorporating disturbance prediction, model uncertainty quantification, pattern learning, and recursive subspace identification for use in controlling complex dynamic systems with periodically recurring large random disturbances. The AL-MPC integrates online learning from historical data to predict the future evolution of the model output over a specified horizon and proactively mitigate significant disturbances. This goal is accomplished using dynamic regularized latent variable regression (DrLVR) approach to quantify disturbances from the past data and forecast their future progression time series. An enveloped path for the future behavior of the model output is extracted to further enhance the robustness of the closed-loop system. The controller set-point, penalty weights of the objective function, and constraints criteria can be modified in advance for the expected periods of the disturbance effects. The proposed AL-MPC is used to regulate glucose concentration in people with Type 1 diabetes by an automated insulin delivery system. Simulation results demonstrate the effectiveness of the proposed technique by improving the performance indices of the closed-loop system. The MPC algorithm integrated with DrLVR disturbance predictor has compared to MPC reinforced with dynamic principal component analysis linked with K-nearest neighbors and hyper-spherical clustering (k-means) technique. The simulation results illustrate that the AL-MPC can regulate the glucose concentrations of people with Type 1 diabetes to stay in the desired range (70–180) mg / dL 84.4% of the time without causing any hypoglycemia and hyperglycemia events. [ABSTRACT FROM AUTHOR]

Insulin plays an important role in the treatment of diabetes. Since it was discovered in the early 1920s, major advances have been made in the medical use of insulin. However, certain insulin associated challenges remain, such as hypoglycemia, weight gain, complex management, and injection site pain. Novel insulins and delivery systems are being developed that can address these limitations. Insulin degludec is a novel basal insulin with a long half-life (25 hours) and action duration (> 42 hours). Glargine U300 is a concentrated formulation of insulin glargine. For improvement in postprandial glucose control, ultrarapid-acting insulins are being investigated. New insulin delivery systems including inhaled insulin and insulin patches are also being developed to overcome the inconvenience associated with subcutaneous injection. In this review, clinical studies of new insulins and new insulin delivery systems are summarized. [ABSTRACT FROM AUTHOR]