Development of inhalatory insulin analogs for diabetes patients

Development of inhalatory insulin analogs for diabetes patients

Diabetes mellitus (DM) is a chronic disease which results in the increased risk of cardiovascular diseases; it is a major cause of blindness, leads to chronic kidney failure, amputations. It appears when the gland pancreas does not produce insulin at the necessary rate in the organism. Express Scripts reads:
“Insulin is a hormone produced naturally by the pancreas.
Insulin lowers the amount of sugar in your blood. Keeping
your blood sugar close to normal prevents or reduces long-
term complications of diabetes including damage to the
blood vessels, eyes, kidneys, or nerves”
The new method of insulinotherapy – inhalation therapy attracts everybody’s attention. Patients try to avoid switching to insulin that results in prolonged clinical course of diabetes with noncompensated hyperglycemia. All in all it is the fear of constant injections.
Inhalation is non-injection method of insulinotherapy, which will surely increase the patients’ adherence to insulin.
Meanwhile, the first experiments with inhalation insulin started in 1924 - two years after the 1st application of insulin. Only in 2006 the first insulin inhalation appeared. His "father" was a biologist John Patton.
The advantages of inhalation method are conditioned by the huge absorbing surface of alveole, which ensures equal distribution and simultaneous dose absorption. It is important to note that inhalation of insulin doesn’t serve as the basal insulin; it is the insulin of short effect. It is important that the speed of inhalatory insulin effect is more predictable, unlike those medicines, whose speed depends on the place of injection. Medscape Today proves this fact:
“Inhaled insulin has a time-action profile that offers a
peak of onset that is similar to rapid-acting subcutaneous
insulin analogs. However, its duration of action is longer,
approaching that of subcutaneous regular insulin.”
Designed inhalation method of introducing insulin is simple enough for the patient; insulin is in powder, packed in special blisters, which are placed in individual apparatus for inhaling the drug. International Diabetes Monitor Archives cites:
“An aerosol is defined as liquid or solid particles
suspended in air. The size of therapeutic aerosol particles
ranges from less than 1 mm to approximately 10 mm in
diameter. Aerosol particles also occur naturally and are
inhaled with every breath. A large proportion of the
inhaled particles will be deposited in the airways and only
some of the smallest particles are exhaled.”
The production of insulin inhalator is rather complex. First, insulin solution is created and then it is dried in a special way, while water is replaced by mannitol or glycerol. The drug is mixed with a small number of filler, then it is divided into doses and placed in the package, which protects against moisture.
Before getting on the absorbent surface of lungs, insulin passes through the bronchial tube, so when the drug reaches alveole, it has the extremely low concentration. During this process insulin must manage to pass the stage of spraying, sedimentation and diffusion. That is why it is necessary to inhale insulin very slowly.
Taking into account the method of application and the way that the drug passes from the mouth to the alveole, one of the biggest problems in the application of inhalatory insulin is its low bioavailability: nearly 30 per cents of insulin remain in the inhalator, nearly 20 per cents – in nasopharynx, 10 per cents – in trachea and only 40 per cents reach the alveole. There are other problems that must be solved by the scientists. They are production of antibodies to insulin, development of hypoglycemia during inhalation application, the dependence of inhaled insulin from a state of the lungs and lung functions, the ability to use insulin inhalation among the patient with bronchial asthma and other obstructive lung diseases, as well as among smokers. As a preliminary it should be said that before the treatment the doctor should examine the patient: to make spirometry and if a patient has significant violations of lung function the doctor should decline the use of insulin inhalations and moreover the patient should necessarily stop smoking. Obstructive lung diseases of non-heavy form are not the contraindication for the use of insulin inhalation, pneumonia is also not considered a contraindication, but the glucose levels be monitored thoroughly.
Thus, one can say that inhalation of insulin can be used among patients with diabetes mellitus of the 1st and he 2nd type. It should be noted that using non-injection method of insulin application, patients follow the treatment course more diligently. The main disadvantage of this method is its very high cost, as well as the limitation of patients.
Bibliography
American Diabetes Association. Complete Guide to Diabetes. Alexandria: American Diabetes Association, 2005.

Bernard L Silverman, Christopher J Barnes, Barbara N Campaigne, and Douglas B Muchmore. Inhaled insulin for controlling blood glucose in patients with diabetes. 2007. Pub Med Central. 1 June 2008. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2350138

Inhaled insulin was a reality. 18 October 2007. The Diabetes Monitor. 1 June 2008. http://www.diabetesmonitor.com/inhaledi.htm

Insulin inhalation powder. 18 October 2007. Express Scripts. 1 June 2008. http://www.drugdigest.org/DD/DVH/Uses/0,3915,8688%7CInsulin%2Binhalation%2Bpowder,00.html

Is Inhaled Insulin as Good as Insulin Shots? 2005. American Diabetes Association. 1 June 2008. http://www.diabetes.org/diabetes-research/summaries/skyler-inhaled-insulin.jsp

John A. Colwell. Diabetes. Philadelphia: Hanley & Belfus, 2003.

Mayer B. Davidson. Diabetes Mellitus: Diagnosis and Treatment. Saunders, 1998.

Per Wollmer. International Diabetes Monitor Archives. 1 June 2008. http://www.d4pro.com/idm/site/physiology_of_inhaled_insulin.htm

Potential Risks Associated With the Inhalation of Insulin. Medscape Today. 1 June 2008. http://www.medscape.com/viewarticle/493575_8

Ruchi Mathur, MD. Inhaled Insulin CME/CE. 2006. Medscape Today. 1 June 2008. http://www.medscape.com/viewarticle/540927