Injectable Nano-Network to control blood glucose level

Diabetes is one of the leading epidemic global public health diseases. An estimated 366 million people get affected across the world at present. It results by accumulation of glucose in blood. In diabetes condition, human body loses the ability to produce enough insulin that fulfills the body requirement (type 1) or body cells fail to respond to the insulin (type 2). Current standard care for type 1 diabetic patients and type 2 diabetic patients needs regular blood glucose levels monitoring and subsequent injections of insulin to attain normal glycemia level. Hypoglycemia results in risks of unconsciousness, seizures, brain damage, or ultimate death occurs. Hyperglycemia causes many serious complications such as kidney failure, limb amputation and blindness. Accurate monitoring the daily fluctuation of glycemia by self-administration (open loop insulin delivery) is painful and poor glucose level.

We need to develop a system that accurately monitors the glucose level in body. Considerable efforts have been concentrated in developing the close loop system that accurately monitors the glucose level according to body conditions. One of the strategies, in close loop insulin delivery, is to combine two techniques sensor activated insulin releasing element and glucose-sensing moiety within one system. A device has been created that works on the base of semiautomatic, in which we combine external insulin infusion pump with continuous glucose-monitoring sensor. Another technique is to develop polymeric biomaterials to achieve chemically controlled closed-loop insulin delivery. In this way we combine the synthetic phenylboronic acid (PBA) and lectin with enzyme glucose oxidase which form the gluconic acid in presence of glucose.

In biomaterial, enzyme is immobilized or entrap in glucose responsive system, it changes its properties in response to change pH level. The pH decreases when blood glucose level increases that changes the properties of biomaterials and release the store insulin. Biomaterial is a composed, injectable polymeric nanoparticle-cross-linked network; dextran is degradable in the presence of acid and biocompatible matrix material. In nano-network we use the nano-particles that formed by the double emulsion (water in oil and oil in water) based, extraction and evaporation method. It has four components .1) acid degradable, 2) polymeric matrix, 3) polyelectrolyte-based surface coatings that have glucose-specific enzyme and 4) recombinant insulin. Dextran is selected because it ease biodegradable, modify and biocompatible and make it water soluble by using different acid catalyze reaction with ethoxypropene using the hydrophilic payload and dextran hydroxyls with m-dextran. M-dextran is easily soluble in solvents which have organic nature used for preparation of emulsion such as acetone and dichloromethane. Ethoxypropene is pH sensitive. Under mildly acidic aqueous it hydrolyze and giving dextran hydroxyl groups. The complete hydrolysis of m-dextran results in regeneration of water-soluble native dextran together with ethanol and acetone, which show insignificant toxicity in small quantities. The enzyme GOx is the glucose-responsive factor for generating pH stimulus, while the CAT is applied to offer oxygen (O2) to assist GOxs catalysis .The weight ratio of GOx to CAT was optimized as 4:1 by analyzing the catalytic capability of enzyme mixtures at different concentrations.

In humans we use two polysaccharide nano-particles which have opposite charged such as chitosan as positive particle and alginate as negative particle. These particles modify the dextran nanoparticle surface and opposite charged dextran particle separated by loading the insulin. Small and uniform size of nano-particle gives the cohesive strength, and also opposite charge gives the tight particle packing as a cause of the electrostatic interaction. These particle loaded by insulin and enzymes by mixing in solution of oppositely charged dextran nanoparticle. To make it injectable via syringe requires low viscosity it achieved by reducing the cohesive force at high shear rate. Under hyperglycemic condition it gradually dissociated due the pH, whose level decreased in blood in result releases the insulin from particles. The insulin release through the nano-network is facilitated at a high glucose level and inhibited at a low glucose level.

In conclusion, we mediated insulin delivery in response to glucose level changes through injectable nano-network. It consists o nanoparticles of oppositely charged dextran sum up with glucoses specific enzymes and insulin. In hyperglycemia condition releases insulin by dissociation in reducing the pH and glucose converted into gluconic acid in the presence of enzymes and the subsequent degradation of the polymeric matrix are facilitated. This formulation design provides a potential delivery strategy for both self-regulated and long-term diabetes management.

The writer is associated with the Wheat Genetics Laboratory, Dept. of Plant Breeding and Genetics, University of Agriculture, Faisalabad, Pakistan. he can be reached at <>

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