Pulmonary Insulin Delivery: Challenges and Current Status

Insulin is usually administered to diabetic patients through subcutaneous injection. However, the various problems are encountered with subcutaneous insulin injection. Insulin cannot be administered via the oral route due to rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes, and poor permeability across intestinal epithelium .Hence various alternative routes for insulin delivery have been investigated. The most promising alternative route of insulin administration seems to be pulmonary delivery by inhalation. However, the issue of short duration of action of drugs delivered through this route has continued to challenge drug formulators and various strategies have been developed. This review gives a detailed, overview of the available literature on the safety and efficacy of inhaled insulin in pre-clinical and clinical trials. Additionally, the potential risks of inhaled insulin, in particular concerning insulin antibodies and lung function parameters will be discussed. INTRODUCTION: Diabetes is a chronic progressive disease, which can lead to complications such as kidney failure blindness and foot amputation, and it is also a major risk factor for coronary heart disease and stroke. There are two main types of diabetes, type 1 and type 2. Type 1 accounts for 15% of people with diabetes in England and develops most frequently in children, young people and young adults. Type 2 accounts for the rest and is most commonly diagnosed in adults over the age of 40, although it is increasingly being diagnosed in younger people. On average, life expectancy is reduced by more than 20 years in people with type 1 diabetes and by up to 10 years in people with type 2 diabetes . Insulin is usually administered to diabetic patients through subcutaneous injection. However, the problems encountered with subcutaneous insulin injections are pain, allergic reactions, hyperinsulinemia, and insulin lipodystrophy around the injection site . Oral delivery of Insulin as a non-invasive therapy for Diabetes Mellitus is still a challenge to the drug delivery technology, since it is degraded due to the presence of enzymes in the acidic environment of stomach and also its absorption through the gastrointestinal mucosa is questionable. Generally, peptides and proteins such as insulin cannot be administered via the oral route due to rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen, and poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity [4-6] Alternative routes for insulin delivery that have been investigated include intrapulmonary intrauterineocular, nasal, buccal,and transdermal systems. However, results to date indicate problems related to poor absorption, high proteolytic degradation, and/or variable delivery times. Consequently, bioavailability is low, and response times are difficult to predict accurately. Since the discovery of insulin over 80 years ago, investigators have sought to develop a pulmonary route of insulin delivery. Major absorption of drugs intended for systemic action after pulmonary delivery occurs from the deep alveolar region. The respiratory tract can be categorized into two major regions: the upper respiratory region called the conducting zone and the lower respiratory region termed the respiratory zone. Nasal cavity, sinuses, nasopharynx, oropharynx, larynx, trachea, bronchi, and bronchioles comprise the conducting zone while the respiratory bronchioles, alveolar ducts and alveolar sacs comprise the respiratory zone. [5] The pulmonary route of administration offers several advantages. The lung offers nearly ideal conditions for the absorption of peptides including a vast (in humans 50 140 m, ~500 millions of alveoli) and well-perfuse Kamlesh Wadher et al /J. Pharm. Sci. & Res. Vol.3(2), 2011,1052-1059