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Insulin Delivery by a Bioartificial Pancreas
Published in Emmanuel Opara, Controlled Drug Delivery Systems, 2020
Pancreatic islet biology is closely tied to gut and liver biology.11 This, therefore, makes it extremely challenging for exogenously introduced insulin to mimic the dynamic patterns of normal insulin secretion.11 The pancreas typically starts to secrete insulin onto the portal vein even prior to food being swallowed, then this is followed by rapid biphasic insulin release that returns to basal levels as the food is absorbed.11 The normal kinetics of insulin release and the flow of insulin first to the liver and the complex interactions that normally occur cannot transpire with subcutaneous administration of insulin.11 Insulin that is delivered subcutaneously has significant and variable delays (approximately 1 hour to peak levels) in entering the blood and limited liver passage.29 Even with CGM, there is a variability in ongoing insulin needs.29
Controlled Release of Therapeutic Proteins
Published in Munmaya K. Mishra, Applications of Encapsulation and Controlled Release, 2019
Arruje Hameed, Tahir Farooq, Kanwal Rehman, Muhammad Sajid Hamid Akash
The multiple emulsion technique has also been used for the preparation of a microsphere formulation of interferon α (IFN-α) in a poly d,l-lactide-polyethylene glycol (PELA) matrix. In the formulation, PELA surrounds the calcium alginate core, and microspheres are encapsulated with IFN-α. The PELA matrix and IFN-α were stabilized by microsphere coating, resulting in the retention of bioactivity for a longer duration with high encapsulation efficiency. So, microsphere production by this method established its superiority over the conventionally practiced methods. Another study described the encapsulation of salmon calcitonin with PLGA microspheres, which demonstrated controlled release in 5 to 9 days after SC injection in rats. The same technique has also been used to prepare insulin-loaded microspheres using blends of poly(lactic acid) (PLA) and PEG homopolymer and PLGA copolymer. The resulting highly efficient microsphere formulation maintained a controlled delivery of insulin for 28 days. In rats, the glucose level remained suppressed for 9 days after the subcutaneous administration of ZnO–PLGA microspheres containing insulin, which confirmed the fast and long-lasting efficiency of the controlled delivery formulation.26
Nanomedicine Clinical and Preclinical Use
Published in Bertrand Henri Rihn, Biomedical Application of Nanoparticles, 2017
Roudayna Diab, Sanghoon Kim, Ileana-Alexandra Pavel, Nadia Canilho, Fernanda Bianca Haffner, Sijin Li, Alain Celzard, Mihayl Varbanov, Emmanuel Lamouroux, Andreea Pasc
Diabetes mellitus type 1 is the most common metabolic disease. Replacement therapy is based on multiple daily subcutaneous injections of insulin, associated with multiple drawbacks. Apart from the burden of frequent injections on patients, lipodystrophy and lipohypertrophy in the injection site are frequent complications. Moreover, subcutaneous injections fail to mimic the physiological secretion of insulin, in which insulin undergoes hepatic first pass effect, resulting in a concentration gradient between portal and systemic circulations. Consequently, insulin subcutaneous administration may lead to hyperinsulinemia and thus predisposes to hypoglycemia and overweight.
Artificial pancreas systems: experiences from concept to commercialisation
Published in Expert Review of Medical Devices, 2022
David L. Rodríguez-Sarmiento, Fabian León-Vargas, Maira García-Jaramillo
The main limitations of current commercial AID systems are related to common user interventions such as CGM calibrations (in the case of M670G), estimation of bolus insulin by carbohydrate counting, or adjustments in system settings, as well as owing to difficulties in coping with rapid changes in insulin requirements that cannot be correctly addressed owing to pharmacokinetic and pharmacodynamic limitations of the subcutaneous administration and corresponding delays in the absorption and action of insulin. Other limiting factors include the size and invasiveness of the device for the patient [131], resistance in using the device by healthcare providers [132–134], high costs that make accessibility difficult [104], and availability of this treatment outside the United States and Europe.
Model Predictive Control of Glucose Concentration Based on Signal Temporal Logic Specifications with Unknown-Meals Occurrence
Published in Cybernetics and Systems, 2020
Francesca Cairoli, Gianfranco Fenu, Felice Andrea Pellegrino, Erica Salvato
The Artificial Pancreas is a wearable device developed to simplify the therapy management for T1DM patients. The main elements of an AP are a Continuous Glucose Monitoring (CGM) system, which provides a real-time measure of glucose level in blood, and a pump, which allows a subcutaneous delivery of insulin. Ideally, a controller has to automatically compute the required amount of insulin starting from the knowledge of blood glucose concentration. Unfortunately, the subcutaneous administration of insulin leads to a delay in its absorption (American Diabetes Association 2013). The resulting effect is a rapid growth of glucose after meal that increases the risk of the hyperglycemia condition (Gingras et al. 2018). The current closed loop devices solve the aforementioned problem by requiring an accurate information about meal carbohydrate-content and meal announcement. These requests are not easy to satisfy, especially for adolescents, and the resulting mistakes can lead to undesirable and dangerous outcomes.
Closed-loop insulin delivery: current status of diabetes technologies and future prospects
Published in Expert Review of Medical Devices, 2018
Due to the reasons mentioned above, there has been an interest in the development of intraperitoneal insulin delivery. However, external CSII devices delivering intraperitoneal insulin, although commercially available are not widely used, due to various practical and clinical issues [22]. Barriers to more extensive use have included high device cost and associated healthcare expenditures, which include surgical and technical inputs, and the development of anti-insulin antibodies in some patients [23]. The MiniMed Implantable Intraperitoneal Pump 2007D (Medtronic, Northridge, CA, USA) is currently the only device for clinical application, and its use is still limited to some European countries under specific clinical circumstances [24]. As such, subcutaneous administration of insulin remains the pragmatic route for insulin-delivery systems in clinical practice, until other routes of delivery can be shown to be practical and efficacious.