Strategies Adopted to Improve Bioavailability of Glibenclamide: Insights on Novel Delivery Systems

Objectives: Diabetes mellitus (DM) is one of the most prevalent chronic diseases worldwide. According to the statistics declared in 2020 by the World Health Organization [WHO], in the year of 1980, 108 million people have been diagnosed with diabetes mellitus worldwide, then, in 2014, that number had increased to 422 million. In 2020, International Diabetes Federation [IDF] has highlighted that; there will be nearly 700 million adults all over the world to be diagnosed with diabetes by the year of 2045. DM is sub-categorized into Type 1 and Type 2 DM. The former is considered as an autoimmune disorder, in which pancreatic β-cells are destructed, impairing insulin production. While Type 2 DM occurs due to loss of cells sensitivity to insulin. Both are associated with a marked increase in the blood glucose level (BGL) and hence, patients need for pharmacological treatment. T2DM is the most common among diabetic patients and its treatment involves the use of different classes like sulphonylureas, miglitinides and thiazolidinediones. Glibenclamide (GB) belongs to sulphonylureas, its low water solubility accompanied with lower bioavailability demands the use of a higher dose to assure proper management of diabetes. However, this is accompanied in some cases by a severe hypoglycemia that might be lethal in some cases. Therefore, finding a proper delivery system that could improve GB solubility is highly recommended. Nano-medicine could be considered as a promising strategy to improve the solubility and hence, bioavailability of GB. This review is exploring and presenting the recent studies performed to either to encapsulate GB into NPs or reduction of its size to the nano-size level, in order to improve its bioavailability. The review also points to the various obstacles facing nano-medicine clinical application and lack of human studies and sufficient long term safety studies suggesting that future work is needed to make a clearer conclusion about the clinical applicability of the nano-delivery of GB. Methods: This review reports a collection of research articles that investigated the use of several nano-delivery approaches for the delivery of GB up to 2022, using internationally accepted scientific journals and databases. Results: This review shows that the delivery of GB using nano-medicine strategy improves the GB aqueous solubility and hence, improves its oral bioavailability. It also shows that nano-medicine approach could sustain/control the release of GB, therefore, maintaining stable plasma drug concentration and avoiding any undesired fluctuation. Conclusion: The results of the collected articles show that the use of the different nano-medicine categories could be promising to overcome the poor bioavailability of GB. The successful clinical application of the liposomal delivery of certain drugs renders liposomes promising carrier for GB, however, because of the several advantages of the niosomes over liposomes, they seem to be a promising alternative. Despite this, there are still several barriers against the large scale manufacture of nano-medicines including niosomes, also, more research is required to confirm the long term safety of clinical application of GB-loaded niosomes.