Accelerated absorption of insulin via a subcutaneously implanted, vascularized micro-chamber

通过皮下植入的血管化微室加速胰岛素的吸收

• 批准号: 10721366
• 负责人: Robert C Johnson
• 金额: $ 30万
• 依托单位: PROCYON TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-03 至 2024-08-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10721366
• 关键词: Acceleration; Animal Model; Animals; Area; Arizona; Blood; Blood Glucose; Blood Vessels; Bolus Infusion; Cannulas; Catheters; Cells; Child; Clinic; Custom; Data; Dermis; Device Designs; Devices; Diffusion; Dose; Drug Kinetics; Engineering; FDA approved; Fatty acid glycerol esters; Formulation; Future; Glucose; Growth; Histologic; Hour; Human; Hypoglycemia; Implant; Infusion procedures; Injections; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; Intercellular Fluid; Kinetics; Laboratories; Life; Measures; Medical Device; Membrane; Needles; NovoLog; Outcome; Pancreas; Patients; Penetration; Permeability; Polyesters; Polyethylenes; Polytetrafluoroethylene; Process Measure; Pump; Raccoons; Reproducibility; Rodent; Safety; Side; Skin; Subcutaneous Injections; Subcutaneous Tissue; Surface; Syringes; Technology; Testing; Therapeutic Effect; Thinness; Time; Tissues; Universities; Vascularization; absorption; blood glucose regulation; clinical translation; design; diabetes control; diabetic patient; diabetic rat; experience; implantation; improved; in vivo evaluation; insulin secretion; life history; manufacture; medical implant; phase 1 study; phase 2 study; preservation; prevent; prototype; seal; subcutaneous; type I diabetic; uptake

Project Summary In Type I diabetic (T1D) patients, insulin is injected into the subcutaneous (SC) tissue, by needle or a pump and SC cannula. A bolus of insulin SC reaches its peak in about one hour or more. This slow absorption is in dramatic contrast to the secretion of insulin into the blood by the normal human pancreas, a process measured in seconds. Consequently, patients with T1D often struggle to control their glucose, experiencing swings into hyper- and hypoglycemia. Faster insulin absorption will greatly improve glucose control in T1D patients, reducing complications in the near and long term. In rodent studies performed in the laboratory of Dr. Papas at the University of Arizona, administering insulin via a subcutaneously implanted vascularized chamber resulted in a Tmax of 7.5 minutes versus 22.4 min after SC injection. If translatable to the clinic, accelerated insulin absorption would greatly improve glucose control. Procyon Technologies LLC proposes to capitalize on these preliminary findings and evaluate the absorption kinetics of insulin delivery through custom-designed, SC-implanted, durable, low-volume microchambers compatible with insulin dosing (which especially in children, is measured in the low µL range, volumes difficult to measure and accurately deliver by syringe and needle). Small doses can be accurately delivered by existing precision insulin pumps, but they do so into the relatively avascular SC space. The Procyon microchambers are specifically engineered to develop a vascular network at the implant-tissue interface to accelerate insulin absorption and can connect with pumps. The chambers will be manufactured with membranes and materials long approved by the FDA for implantable medical devices (e.g., PTFE, polyester, and polyethylene). We propose the following three Specific Aims (SA), to be investigated in a diabetic rat model. SA1: To manufacture and bench test fixed volume (5L) Procyon microchambers with three different vascularized surface area to volume ratios (A/V) for in vivo testing in SA 2. We hypothesize that a critical design parameter for subcutaneously implanted, vascularized microchambers is the A/V ratio. This Aim will quantify the impact of this parameter for future device designs. SA2: To compare pharmacokinetics of the three microchamber configurations fabricated in SA1 versus subcutaneous injection of insulin. Reproducible, detailed pharmacokinetic data, obtained after a single dose of regular human insulin (NovoLog), injected SC or into a vascularized microchamber, will be compared over a period of 3 months. SA3: To evaluate histologically the “life history” of the three Procyon microchamber configurations tested in vivo in SA2 over a period of 3 months. These studies focusing on evaluating the maturing vascularization at the implant- tissue interface will provide information about durability, safety and, especially, the continued functionality of delivering insulin via a microchamber over months. Successful completion of these aims will frame device configurations for future studies in large animals and ultimately humans.

项目总结