Abstract
Current oral insulin formulations reported in the literature are often associated with an unpredictable burst release of insulin in the intestine, which may increase the risk for problematic hypoglycemia. The aim of the study was to develop a solution based on a nanolayer encapsulation of insulin-chitosan complexes to afford sustained release after oral administration. Chitosan/heparin multilayer coatings were deposited onto insulin-chitosan microparticulate cores in the presence of poly(ethylene) glycol (PEG) in the precipitating and coating solutions. The addition of PEG improved insulin loading and minimized an undesirable loss of the protein resulting from redissolution. Nanolayer encapsulation and the formation of complexes enabled a superior loading capacity of insulin (>90%), as well as enhanced stability and 74% decreased solubility at acid pH in vitro, compared with nonencapsulated insulin. The capsulated insulin administered by oral gavage lowered fasting blood glucose levels by up to 50% in a sustained and dose-dependent manner and reduced postprandial glycemia in streptozotocin-induced diabetic mice without causing hypoglycemia. Nanolayer encapsulation reduced the possibility of rapid and erratic falls of blood glucose levels in animals. This technique represents a promising strategy to promote the intestinal absorption efficiency and release behavior of the hormone, potentially enabling an efficient and safe route for oral insulin delivery of insulin in diabetes management.
Highlights
Insulin is the major protein hormone synthesized by the β cells of the pancreatic islets of Langerhans
We established that insulin microparticles could be formed either by precipitation in the presence of nonionic polymer (PEG) or by complexes of insulin with chitosan
By the addition of chitosan into the poly(ethylene) glycol (PEG) solution, a 98.5% insulin-association efficiency could be achieved with an insulin content of 90.9% in the insulin-chitosan microparticles
Summary
Insulin is the major protein hormone synthesized by the β cells of the pancreatic islets of Langerhans. It is essential for the treatment of type 1 diabetes and is often needed for optimal control of type 2 diabetes mellitus. It is usually administered to diabetic patients by subcutaneous injection. An oral delivery route of insulin would be the most convenient, comfortable, and patient-preferable means of administering the hormone.
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