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How the novel on-skin artificial pancreas can ease diabetes problems?

Artificial Pancreas for Diabetes

Diabetes is sixth leading cause of death.  According to WHO’s Global Report on Diabetes, in 2016, an estimated 1.6 million deaths were directly caused by diabetes. The chronic disease caused due to pancreas inefficiency to produce enough insulin is capturing higher number of people every year. The same research explains that the number of people with diabetes has risen from 108 million in 1980 to 422 million in 2014, which is a drastic 4 times growth.

The traditional method to treat diabetes via insulin injection not only involves pain, inconvenience, infection and nerve damage, but also is difficult to achieve persistent glycemic control. Therefore, there is a great need for an alternative method to manage the insulin doses.An artificial pancreas has the potential to relieve the person with diabetes from some of the these key issues with traditional methods by automating detection of blood sugar levels and delivery of insulin in response to those levels and providing optimal blood glucose control with minimal effort and reducing the potential for disease complications.

What is Artificial Pancreas?

Artificial Pancreas is nothing but a system of devices that closely imitates the glucose regulatory functions of healthy pancreas. The glucose management inside the human body is considered as open-loop activity. This technology is consisting of a feedback control instrument that regulates insulin delivery. The Artificial Pancreas device system has got several names like ‘Closed-loop system’, or ‘automated insulin delivery system’, or ‘autonomous system for glucose control’

Most of the Artificial Pancreas Device System consists of a continuous glucose monitoring system (CGM) and an insulin infusion pump. A blood glucose devise such as glucose meter is used to calibrate the CGM. Algorithm controlled by a computer is connected to CGM and insulin infusion pump. This provides the continuous communication between two devices. This technology monitors glucose levels in the body as well as automatically adjusts the delivery of insulin to reduce glucose levels preventing hyperglycemia. It will also prevent hypoglycaemia by diminishing the low blood glucose levels.

The various functions of various parts of the system:

  1. i) Continuous Glucose Monitor:

A CGM is used to provide information of patient’s blood glucose level. The sensor positioned under patient’s skin measures the glucose in the fluid around the cells. This information is sent further to a receiver with the help of a small transmitter.

  1. ii) Control Algorithm:

It is software embedded in an external processor or controller which receives the information from CGM and performs various mathematical calculations. The controller sends instructions to infusion pumps on the basis of calculations. The control algorithm can be performed by number of devices like computer or cellular phone etc.

iii) Insulin Pump:

An infusion pump adjusts the insulin delivery to the tissue under the skin as per the instructions sent by the controller.

iv)Patient:

It is the most important part of the system. The whole system might get affected by the diet and activities and metabolism of the patient.

A successful artificial pancreas will make life changing advancement for many people with type 1 diabetes. Still there are some disadvantages of this technology.

This Artificial Pancreas—aka “closed-loop” delivery systems are either electronics-derived or protein-based, leading to the concerns of electrical failure or immunetoxicity.Therefore, to deliver insulin in a glucose-responsive, painless, convenient, and safe way, scientists have developed an electronics-free, enzyme-free smart artificial “on-skin pancreas”Prof. Akira Matsumoto from Medical and Dental University and the Kanagawa Institute of Industrial Science and Technology, along with his co-workers thoroughly investigated and made a report on stable, long-acting insulin delivery technology called as artificial on-skin pancreas.

Why should diabetes patients go for on-skin artificial pancreas?

The on-skin pancreas is electronics free, enzymes free, a microneedles (MNs) patch fabricated with smart hybrid hydrogel and silk fibroin. Silk fibroin is derived from silkworm cocoons. It is designed in a way that it will deliver insulin in a convenient and safe way. It will be painless and glucose responsive.

The hydrogel is contained in MNs and it allows glucose-responsive diffusion control of insulin which corresponds to the change in hydration on the gel surface called as ‘skin layer’ formation. The silk fibroin magnifies the mechanical strength of the MNs and facilitates skin penetration.

Working mechanism of on-skin artificial pancreas

In this technology Phenylboronic acid (PBA) is assigned with the major role. PBA binds with glucose reversibly and works aptly for glucose sensing and self-regulated insulin delivery purpose. Moreover, it does not have immunetoxicity and denaturing concerns. The semi-interpenetrating network hydrogel is fabricated using PBA derivative. N-isopropylacrylamide and silk fibroin brings in the mechanical robustness. Hybrid hydrogel is put on the tip region of MNs surface for continuous monitoring of the glucose level after insertion. The skin layer that forms on the MNs surface will efficiently block the release of insulin at the normoglycemic condition. Conversely, as the glucose concentration increases the binding of PBA with glucose leads to the hydration of the hybrid MNs and this allows the release of insulin at hyperglycemia condition.

Micro-molding technology

Moreover, micro-molding technology enabled the fabrication of two-layer MNs with silk fibroin as the base layer and hybrid hydrogel in tip region. Here an insulin reservoir is attached to intensify the amount of loaded insulin.  The MNs patch is effectively penetrated in the skin and released insulin in accordance with the external glucose concentration.

This novel on-skin pancreas has the potential to be the next-generation therapy for diabetes because it is patient-friendly, possible to achieve persistent glycemic control, durable and disposable.

More reasons to accept this innovation

According to Dr. Akira Matsumoto,the most remarkable advantage of this technology is that it is remarkably stable, while providing both fast and long-acting glucose-responsive insulin delivery. It can overcome the limitations associated with current technologies such as short duration of action, instability, and possible toxicity.

Reference Paper:

  1. Siyuan Chen, Hiroko Matsumoto, Yuki Moro‐oka, Miyako Tanaka, Yuji Miyahara, Takayoshi Suganami, Akira Matsumoto. 2018. Microneedle‐Array Patch Fabricated with Enzyme‐Free Polymeric Components Capable of On‐Demand Insulin Delivery. [2018 December 09; accessed 2019 Feb 18].