Abstract
Diabetes mellitus is a chronic endocrine disease, affecting more than 400 million people around the world. Patients with poorly controlled blood glucose levels are liable to suffer from life-threatening complications, such as cardiovascular, neuropathy, retinopathy and even premature death. Today, subcutaneous parenteral is still the most common route for insulin therapy. Oral insulin administration is favourable and convenient to the patients. In contrast to injection route, oral insulin delivery mimics the physiological pathway of endogenous insulin secretion. However, oral insulin has poor bioavailability (less than 2%) due to the harsh physiological environment through the gastrointestinal tract (GIT). Over the last few decades, many attempts have been made to achieve an effective oral insulin formulation with high bioavailability using insulin encapsulation into nanoparticles as advanced technology. Various natural polymers have been employed to fabricate nanoparticles as a delivery vehicle for insulin oral administration. Chitosan, a natural polymer, is extensively studied due to the attractive properties, such as biodegradability, biocompatibility, bioactivity, nontoxicity and polycationic nature. Numerous studies were conducted to evaluate chitosan and chitosan derivatives-based nanoparticles capabilities for oral insulin delivery. This review highlights strategies that have been applied in the recent five years to fabricate chitosan/chitosan derivatives-based nanoparticles for oral insulin delivery. A summary of the barriers hurdle insulin absorption rendering its low bioavailability such as physical, chemical and enzymatic barriers are highlighted with an emphasis on the most common methods of chitosan nanoparticles preparation. Nanocarriers are able to improve the absorption of insulin through GIT, deliver insulin to the blood circulation and lower blood glucose levels. In spite of some drawbacks encountered in this technology, chitosan and chitosan derivatives-based nanoparticles are greatly promising entities for oral insulin delivery.
Highlights
Diabetes mellitus (DM), one of the major epidemics worldwide of the 21st century, is a chronic disease that developed in about 451 million people in 2017 and this number is anticipated to increase to 693 million by 2045 worldwide [1,2]
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Summary
Diabetes mellitus (DM), one of the major epidemics worldwide of the 21st century, is a chronic disease that developed in about 451 million people in 2017 and this number is anticipated to increase to 693 million by 2045 worldwide [1,2]. Mere oral administration of insulin is encountered with enzymatic and physiological barriers that negate insulin absorption through intestinal epithelial cells Such hurdles render insulin poor oral bioavailability, despite the oral route is the most favourable mode of diabetes management [1]. In the last two decades, great interest was granted to polymeric and lipid-based nanoparticles over inorganic metal ones for proteins/peptides oral delivery, owing to their biocompatibility and biodegradability, as well as promising clinical outcomes [7,8]. What makes chitosan unique over other polysaccharides for oral drug delivery is its chemical structure that allows specific modifications through modulation in the chitosan amine or hydroxyl functional groups [16]. This review will discuss how recent developments in chitosan/chitosan derivatives-based nanotechnology have been emerged in a multitude of platforms for safe and efficient delivery of insulin orally for the treatment of DM
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