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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]

Open source closed loop automated insulin delivery (CL-AID) systems are increasingly used in the treatment of diabetes. Not being officially approved, such systems are used by patients on their own initiative. Accordingly, the medical community has very little information about the treatment satisfaction and needs of patients that use these systems. We conducted an anonymous internet survey of Russian users of open source CL-AID systems. Ninety-five respondents reported using AndroidAPS (60%), FreeAPS X (16.6%), Loop (10.5%), FreeAPS (5.3%), OpenAPS (3.2%), and Omnia (2.1%). The duration of use of the systems ranged from 0.1 to 6 years (median 2.1 years). The mean HbA1c in users was 6.1% v.s. 7.3% on previous therapy. Most respondents reported an increase in Time in Range (88%), a decrease in the number of hypoglycemic episodes (73%), an improvement in the sleep quality (76%), general well-being (73%), social adaptation (56%) and self-confidence (69%), as well as a decrease in stress levels (56%) after switching to the systems. Ninety (94%) survey participants reported increase in the treatment satisfaction. The majority of respondents (68%) consider themselves advanced gadget users. However, 79% of them had technical difficulties when setting up the system for the first time, 46% had difficulty understanding the settings of the algorithm / program, and 35% spent a lot of effort studying the system. Support from the attending physician was reported by 27% of respondents, 35% noted the neutral attitude to the use of the system, and in 18% of cases the doctor was not aware of its use. All respondents, with the exception of two who found it difficult to answer, plan to continue using the system. Thus, from the patient's point of view, open source CL-AID systems have a positive effect on glycemic control and quality of life. The medical community should pay more attention to the needs of patients using these systems in treatment.

Open source closed loop automated insulin delivery (CL-AID) systems are increasingly used in the treatment of diabetes. Assembled on a do-it-yourself (DIY) basis, these systems integrate insulin pumps, continuous glucose monitoring devices, and algorithms that control the rate of insulin delivery based on glucose levels. In this review, we consider the technological features of open source CL-AID systems (OpenAPS, AndroidAPS, Loop, etc.), advantages and barriers to their use in clinical practice. Advantages of open source CL-AID systems over commercially available ones included lower cost, a choice of devices, a wide range of user settings, as well as continuous improvement of algorithms. A growing body of evidence indicates that open source CL-AID systems, such as OpenAPS, AndroidAPS, and Loop, provide an excellent time in range with minimal risk of hypoglycaemia and increase treatment satisfaction in patients with type 1 diabetes. A wide range of settings makes open source systems an effective tool for managing diabetes in situations with rapidly changing insulin requirement. However, some technological, medical, legal and ethical issues associated with the use of non-commercial CL-AID systems still need to be addressed. Assembling the system requires skills in diabetes technology. The issue of cybersecurity is also relevant. Lack of official approvals, low awareness of medical professionals, and reimbursement issues are slowing down the introduction of the technology into clinical practice. The professional medical community at the international and national levels needs to determine its position regarding the use of open source CL-AID systems in the treatment of diabetes.

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.

Introduction: Diabetes is a growing epidemic worldwide and requires effective clinical therapies. In recent years, β-cell transplantation has emerged as a promising treatment for diabetes, and an encapsulation approach has been proposed to ameliorate this treatment.Methods: Microfluidic technology had been used to generate microcapsules using a porous sodium alginate shell and a core containing β cells. The microcapsules were transplanted into diabetic mice and the therapeutic effect was measured.Results: Porous hydrogel shell allows exchange of small molecules of nutrients while protecting beta cells from immune rejection, while the core ensures high activity of the encapsulated cells. The glucose control effect of the microcapsules were more durable and better than conventional methods.Discussion: We believe that this system, which is composed of biocompatible porous hydrogel shell and enables highly activity of encapsulated β cells, can enhance therapeutic efficacy and has promising clinical applications.

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. [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]

Introduction: Diabetes is a growing epidemic worldwide and requires effective clinical therapies. In recent years, β-cell transplantation has emerged as a promising treatment for diabetes, and an encapsulation approach has been proposed to ameliorate this treatment. Methods: Microfluidic technology had been used to generate microcapsules using a porous sodium alginate shell and a core containing β cells. The microcapsules were transplanted into diabetic mice and the therapeutic effect was measured. Results: Porous hydrogel shell allows exchange of small molecules of nutrients while protecting beta cells from immune rejection, while the core ensures high activity of the encapsulated cells. The glucose control effect of the microcapsules were more durable and better than conventional methods. Discussion: We believe that this system, which is composed of biocompatible porous hydrogel shell and enables highly activity of encapsulated β cells, can enhance therapeutic efficacy and has promising clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luo, Dong, Yu, Fu, Qiu, Sun and Chu.)

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]

Poorly controlled diabetes before conception and during pregnancy among women with pre-existing diabetes can cause major birth defects and spontaneous abortions, as wells as abnormal fetal growth and development including an offspring who is small or large for gestational age, or predisposed to obesity, type 2 diabetes, and metabolic syndrome in his/her lifetime. Conversely, for a woman with pre-existing diabetes, optimizing blood glucose levels before and during early pregnancy can reduce these risks dramatically. As insulin pump technology has evolved, continuous subcutaneous insulin infusion has become a safe and reliable method for treating diabetes during pregnancy. Although pump therapy is often preferred by patients and some experts, insulin pumps have not yet been shown to be superior to multiple daily injections of insulin during pregnancy. In this review of the literature we focus on the use of insulin pumps in the management of diabetes in pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: Many environmental conditions can influence the mechanical characteristics of the glucose-sensitive hydrogels. In this paper, a multi-effect-coupling glucose-stimulus (MECglu) model is developed to study the influence of environmental solution pH on the swelling behavior of soft smart hydrogels responding to change in surrounding blood glucose concentration. In order to characterize the chemo-electro-mechanical behaviors of the hydrogels, the model is composed of the Nernst–Planck type of diffusion-reaction partial differential equations for mobile species with consideration of the enzyme reaction catalyzed by the glucose oxidase and the catalase, the Poisson equation for electric potential, and the nonlinear equilibrium equation for mechanical large deformation of the glucose-sensitive hydrogel. In the MECglu model, the formulation of the fixed charge groups bound onto the corsslinked polymeric network is associated with the change of the ambient solution pH. Using these nonlinear coupled partial differential equations, we demonstrate that the computational mechanical deformation by the MECglu model consists well with the experimental observations published in the range of practical physiological glucose concentration from 0 to 16.5mm (300mg/ml). The simulations are also carried out for analysis of the influences of physiological pH on the distributive profiles of reacting and diffusive species concentrations and the electric potential as well as the mechanical deformation of the glucose-sensitive hydrogels. The simulations by the model can efficiently support the design and optimization of the insulin delivery system based on the glucose-sensitive hydrogels with the immobilized glucose oxidase and catalase. [Copyright &y& Elsevier]

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.)