Insulin was isolated in 1921 from animal sources by Canadian scientists Frederich G. Banting and Charles H. Best. Ever since it was discovered, researchers have been searching noninvasive (i.e. needle-free) ways to deliver insulin to people who have diabetes. Insulin, a hormone, is secreted by beta cells in the pancreas and insufficiency of insulin in the body results in diabetes. People with diabetes (mainly insulin dependent) take insulin to control blood glucose levels. Insulin cannot be taken orally, because like any other protein, it would be destroyed to its amino acid components in GIT by digestion. Therefore, insulin, a macromolecule, is usually administered as subcutaneous injection by various injection devices, adversely affecting patient's quality of life and compliance. The most commonly used delivery device is single-use syringe. Others are repeated-use insulin pens, insulin jet injections, and insulin pumps.
Historical events
The importance of insulin isolation from animal sources and its potential use were recognized way back in 1923, when Macleod and Banting were awarded Nobel Prize in Medicine or Physiology by Swedish Academy. It was the first protein for which the exact sequence of amino acids (structure) was determined by British biologist Frederick Sanger. For this discovery, he was awarded Nobel Prize in Chemistry in 1958. Human insulin differs by three amino acids from bovine insulin and only one from the porcine form. For nearly 60 years bovine and porcine insulins were used. In 1978, Genentech (a biotech manufacturer) produced human insulin in Escherichia coli in the laboratory using recombinant DNA (rDNA) technology. It was only second occasion a human gene was inserted in bacterial cell. In 1982, recombinant insulin was approved by FDA as Humulin. Incidentally Humulin became the first genetically approved drug. In 1981, another pharmaceutical company Novo Nordisk converted chemically and enzymatically animal insulin to human insulin (called semi-synthetic human insulin). More recently, genetic engineering is being used to create insulin analogs that differ in a few amino acids as a way to control their onset and duration of action.
Insulin in diabetes treatment
Since the 1920s, patients have depended on injections of insulin to help keep glucose levels in control. Insulin does this by preparing cells to admit the sugar. The insulin injections available in the 20th century had to be injected frequently since they were quick-acting. Modifications in formulations of injection solutions gave insulin solutions a more flexibility in activity including much needed prolong action. Many people with diabetes use insulin pens or jet insulin injections. Some control their insulin levels to be delivered in the body via portable insulin pumps. The discomfort associated with injection of insulin and patients' agony of self-administration still remains the main problem in diabetes treatment.
Recent reports predict diabetes may become a global burden. And many warn that for the foreseeable future, diabetes will remain a progressively worsening disease that can cause devastating complications. A study from a global database collected by WHO estimates worldwide increase in the number of patients with diabetes, from 135 million in 1995 to 300 million in the year 2025. The highest increase in the prevalence of diabetes is estimated to occur in China (68%) and India (59%) between 1995 and 2025. Since there are no efficient and practicable methods to prevent the manifestations of type 1 and type 2 diabetes, the choice still remains effective insulin therapy.
Inhalable insulin
Inhalable insulin has made many times news headlines in the past months. The US FDA has approved in January this year an inhaled form of insulin, the first new method for delivering insulin into body without needle. The new approved inhalable form of insulin is Pfizer's Exubera (brand name), which Pfizer plans to begin marketing very soon. Many health care providers across the globe have taken keen interest in this noninvasive approach to deliver insulin to people who have diabetes.
What is pulmonary delivery?
It is a method of delivering insulin through the lung by inhalation via mouth, the so-called inhalable insulin. Till recently, most people thought of pulmonary delivery as a topical method for respiratory diseases such as asthma. However, the observation that all asthma drugs are absorbed systematically had led to the idea of application of insulin in an inhalable form. The concept of pulmonary delivery can offer a lot of potential advantages, including a noninvasive alternative to injections, fewer systemic side effects, faster onset of medication, and avoids first-pass metabolism in the liver. Pulmonary insulin delivery systems can be either solution or dry powder formulations, which are delivered through different inhaler systems. Pfizer's Exubera is rapid-acting insulin in powder form. It is delivered with an inhaler of aerosol delivery system; much the same way drug to treat asthma is delivered. Studies so far show that Exubera works to be safe with short-term use. Exubera is approved for people 18 years old and above. However, researchers are interested to know its long- term safety from the results of post marketing surveillance study. Despite the distant apprehensions, the development of inhalable insulin and its subsequent approval is among the most interesting therapeutical options of diabetic management. The new approval of Exubera not only has the potential to fundamentally change the diabetes paradigm, but also has led to conclusive evidences that other drugs including macromolecules (peptides and proteins) could be delivered through lung.
(The author is Reader in Pharmacy, Annamalai University, Annamalai Nagar 608 002, (TN)
Email: cdl_scbasak@sancharnet.in)