Non Invasive Approach for Insulin Delivery: A Mini Review

1Department of Pharmaceutical Analysis, Vathsalya college of Pharmacy, Hyderabad, India 2Department of Pharmaceutics, Vijay College of Pharmacy, Nizamabad, India 3Deparment of Biotechnology, Meerut Institute of Engineering Technology, Meerut, India 4Department of Pharmaceutics, G. Pulla Reddy College of Pharmacy, Hyderabad, India 5Department of Biotechnology, Chaitanya Bharathi Institute of Technology, Hyderabad, India


Introduction
Diabetes patients cannot produce sufficient insulin which is required to convert sugar, starches and other food source into energy. Insulin plays a major role in glycemic control. Various approaches that are currently available for the insulin delivery include insulin syringes, insulin infusion pumps, jet injectors and Pens. Most commonly preferred method is by subcutaneous injections. Major drawback of current forms of insulin therapy is their "Invasive nature". In case of diabetes mellitus Type I for an effective glycemic control patient requires about 3 or more insulin injections a day. In order to overcome the suffering and improve patient compliance, scientists have been looking for effective ways to deliver insulin into blood stream (exogenously). Several Non-Invasive approaches for insulin delivery have been explored which includes Transdermal, Buccal, Oral, Pulmonary, Nasal, Ocular, Rectal routes [1].

Insulin patches
It enables the delivery of insulin through skin. It is a beneficial route of administration because of low proteolytic activity of skin, moreover shows a long lasting effect by maintaining steady blood insulin levels for prolonged period of time. Because of its large molecular size insulin can't effectively penetrate across stratum corneum. Various strategies have been developed which can improve the effectiveness of transdermal route which includes use of penetration enhancers in the formulation, iontophoresis, electroporation, ultrasound, magnetophoresis. Various formulations have been developed for this technique of delivery which are under clinical investigation for their effectiveness [2].

Ocular route
Enormous research studies reveal that ocular route can be utilized as a non-invasive means of delivering drugs systemically.

Oral route of insulin delivery
This route of administration is limited for insulin delivery because of its large molecular size, and enzymatic degradation in the GIT. Various researches have tried to overcome these barriers and promote the oral bioavailability of insulin, which includes entrapment of insulin in micro particles, simultaneous administration of protease inhibitors, coating of insulin with chitosan which stabilizes degradation thereby improves permeability and absorption. Coating of insulin with PH independent Eudragit can improve bioavailability up to 13-14% when compared to intraperitonially administered insulin.

Nasal route
Due to its high epithelial permeability and patient compliance this route is well established for delivery of proteins and peptides. L-Penetratin which acts as a cell penetrating peptide improves the absorption of insulin with a bioavailability of 76% [3].

Inhaled insulin
Pulmonary route is widely used for the treatment of respiratory disorders. Due to its large surface area lungs offer the best route for insulin delivery. Various pumps are available in the market and few formulations are still under clinical investigation for its approval.

Buccal insulin delivery
This is another sophisticated route as an alternate for insulin injections. Few benefits by this route include high patient compliance, robustness of mucosal membrane [4]. Oral-lyn® is a unique oral formulation of insulin that is delivered via the RapidMist® device directly to the mouth, where it is rapidly absorbed into the bloodstream through the buccal mucosa.

Self-regulated insulin
This is designed to release insulin in response to blood glucose level. Hydrogels loaded with glucose oxidase is an example, in which glucose oxidase acts as a glucose sensor and pH sensitive hydrogel acts as insulin release controller. This is the best technique which improves patient quality by reducing the frequency of administration [5].

Conclusion
Diabetes Mellitus is reaching potentially epidemic proportions in India. The quest to eliminate the needle from insulin delivery and to replace it with non-invasive route has begun serious pharmaceutical research which unfolded numerous methods. Though every method has its own pros and cons, few of them are under clinical investigation for their practical applicability. This review summarizes different effective ways of non-invasive routes of insulin delivery.