Formulation, physicochemical characterization and in vitro evaluation of human insulin-loaded microspheres as potential oral carrier

In the past few decades, a significant interest has been focused in formulation and delivery of proteins and peptide drugs for various diseases. A sophisticated pharmaceutical technology is required for production development of these types of drugs, not similar to conventional drugs. Insulin is the most important drug candidate, which is well characterized amongst the therapeutic proteins and peptides derived from recombinant DNA technology. Insulin was isolated from bovine pancreas for the first time in 1922 by Frederick Banting and Charles Best. The aim for delivering exogenous insulin in patients with diabetes is to imitate as closely as possible the normal physiological insulin secretion as in healthy humans (George and Abraham 2006 ). Conventional insulin treatment is basically a replacement therapy for the management of diabetes, wherein insulin is exogenously administered by the subcutaneous route to secrete it as in non-diabetic pancreatic secretion. Insulin delivery by subcutaneous route has been extensively used and explored until now. Parenteral routes are satisfactory in terms of efficacy in the great majority of cases. However, they can result in peripheral hyperinsulinemia, the stimulation of smooth muscle cells proliferation, and the incorporation of glucose into the lipid of arterial walls, which can cause diabetic micro and macroangiopathy (Adameova and Dhalla 2014 ). In addition to this, pain of daily injections, physiological stress, inconvenience, cost, risks, infection, inability to handle insulin, and the localized deposition of insulin, leading to local hypertrophy and fat deposition at the injection sites are some of the problems for administration by parenteral route (Khafagy et al. 2007 ). With the advancement of recombinant DNA technology, it has become conceivable to develop well-defined recombinant human therapeutic proteins (Torosantucci et al. 2014 ). Due to its synthesis, insulin obtained by recombinant DNA technology, large quantities of insulin crystalline powders are available at an affordable price. This is the most important factor that has made insulin to be one of the most popular proteins to be studied for non-parenteral deliveries. Consequently, the results of research into several aspects of the delivery of the insulin are available. These days, there has been a lot of interest in the investigation and feasibility of non-invasive routes for insulin delivery and their product developments in the pharmaceutical industry. These non-invasive routes (Khafagy et al. 2007 ) include oral (Al-Remawi et al. 2017 ), nasal (Bloch et al. 2017 ), buccal (Kumria and Goomber 2011 ), pulmonary (Pfützner and forst 2005 ), transdermal (Leeladurga et al. 2016 ), ocular (Lee et al. 2002 ) and rectal (du Plessis et al. 2010 ) drug delivery systems (Owens 2002 ; Cefalu 2004 ).