Our newly proposed therapy shall contribute to better control of blood glucose levels in patients, leading to optimum management of DM. Named Smart Oral Insulin Therapy, this newly developed therapeutic recombinant construct contains an insulin gene and a regulatory promoter. This special promoter expresses insulin in a temporary, regulatable manner and is also sensitive to blood glucose level. For this purpose, an incretin hormone which is secreted by gut cells in response to high nutrients level is used. The promoter of this hormone gene was employed to create the therapeutic constructs. The constructs are then made into nanoparticles using chitosan as nanocarrier. The fact that this nanocarrier is of carbohydrate based chitin source otherwise known as chitosan, it is proven to be safe even for long term consumption. This new ongoing research treatment of DM is not only the first of its kind that is able to regulate the secretion of insulin mimicking physiological insulin secretion but it also escapes the cumbersome need for injection and glucose monitoring procedure as it is targeted to be taken orally.
Diabetes mellitus (DM) is a vicious, silent killer. There are two main types of diabetes: type 1 and type 2.
Type 1 diabetes is often referred to as insulin-dependent diabetes. In type 1 diabetes, the pancreas (a small gland behind the stomach) does not produce any insulin, causing the patients to take insulin injections for life. In type 2 diabetes, the pancreas does not produce enough insulin, or the body's cells do not react to it properly. Type 2 DM patients especially those with chronic uncontrolled glucose levels will eventually develop a condition known as pancreas exhaustion resulting in cessation of insulin production. As a result, insulin is and will always be the key variable in DM intervention.
Insulin was initially sourced by isolating it from animal pancreatic tissue. However, it was not entirely an effective solution because of immunogenicity of animal insulin. Immunogenicity may elicit an immune response whereby in very bad cases can lead to adverse effects. As such, insulin is now prepared through recombinant DNA techniques using microorganisms.
Currently, the only standard therapy for type 1 DM and type 2 DM-induced-hyperglycemia (advanced stage) is injection of this externally produced synthetic insulin. The injection is repeated daily in certain doses as a lifelong therapy. Ideally, patients have to first prick their finger to test the level of glucose in their blood. This is important because blood glucose level is influenced by many factors such as current diet, physical activity, stress or other illness.
Once the blood glucose level is determined, insulin dose is titrated accordingly and injected into the patient. For a patient with a very high blood glucose level, this exercise may be repeated up to four times daily. As a result, it can be tiresome, fearsome and traumatic to some patients, especially the young ones. Thus, for optimum control, strict monitoring of blood glucose level has to be carried out and this involves finger pricking or vein puncturing.
As a result, diabetic patients are hesitant to commence insulin therapy. This hesitation is due to the mode of insulin administration, a subcutaneous injection as well as the idea of having to sample their blood regularly. Patients would prefer non-invasive modes of treatment such as the oral hypoglycaemic agents.
The difficulty with oral insulin idea to date is finding a way to protect the delicate insulin proteins from being destroyed by the digestive system. There are a few oral insulin ideas which are still under research and development stage studied by multiple research and pharmaceutical centers worldwide. However, these ideas still require glucose monitoring to tailor suit the glucose level to the dose of insulin intake thus forfeiting the whole idea of escaping the needles.
With respect to the above mentioned unfriendly factor and many scientific issues; improved, dynamic approach to the therapy that is efficacious, accurate, needle and hassle free, cheap and above all, does not pose any threat to patients is called for.
This treatment is sustainable and cheap. Since DM is a chronic lifelong disease, the cost of treatment will be a factor that determines its success. Comparing the cost of syringes, needles, blood glucose tests and insulin to the therapeutic nanoparticle pills that are being developed, patients only have to pay two third of the initial cost. Furthermore, with this new innovation, patients are no longer burdened with the need to carefully store their insulin in the refrigerator. Instead, the new therapeutic nanoparticle pills can be left at room temperature in their original bottle and can be taken along anywhere if patients are travelling. The other added value of this invention is that patients only have to take a pill once every 2 days instead of the daily injections.
Once the pill is taken, the nanocarriers protect the therapeutic constructs so that they reach the gut safely. At the gut, although all cells uptake the constructs, only targeted cells express the production of mature insulin when required. This is the best part of the innovation where the ‘smart’ nanoparticles will only produce mature, active insulin, when the gut detects high, abnormal levels of blood glucose, amino acids and fatty acids. If the levels of the nutrients are within the normal range, insulin from the construct will not be produced. These newly developed therapeutic nanoparticles have been tested on mice and rats. In both models, the nanoparticles were able to lower the blood glucose levels of the diabetic animals. RT- PCR, QRTPCR, ELISA, Immunohistochemistry and Western-blot data have supported this idea positively. Ongoing research is being carried out on bigger animals. After the completion of the toxicology studies, we hope to continue research of this invention in clinical setting.