Drug delivery systems for diabetes treatment Running title: Delivery systems for insulin.

BACKGROUND: . Insulin is essential for the treatment of Type 1 diabetes mellitus (T1DM) and necessary in numerous cases of Type 2 diabetes mellitus (T2DM). Prolonged administration of anti-diabetic therapy is necessary for the maintenance of the normal glucose levels and thereby preventing vascular complications. A better understanding disease per se and the technological progress contribute the development of new approaches with the aim to achieve better glycemic control.

OBJECTIVE: Current therapies for DM are faced with some challenges. The purpose of this review is to analyze in detail the current trends for insulin delivery systems for diabetes treatment.

RESULTS: Contemporary ways for management of both types of diabetes by adequate application of drug via subcutaneous, buccal, oral, ocular, nasal, rectal and pulmonary ways. Development of the improved oral administration of insulin is beneficial regarding mimicking physiological pathway of insulin and minimizing the discomfort of the patient. Various nanoparticle carriers for oral and other ways of insulin delivery are developing. Engineered specific properties of nanoparticles (NP): controlling toxicity of NP, stability and drug release, can allow delivery of higher concentration of drug to the desired location.

CONCLUSIONS: The successful development of any drug delivery systems relies on solving three important issues: toxicity of nanoparticles, stability of nanoparticles, and desired drug release rate at targeted sites. The main goals of future investigations are to improve the existing therapies by pharmacokinetic modifications, development of a fully automatized system to mimic insulin delivery by the pancreas and reduce invasiveness during admission.