Nanoparticles for Oral Delivery of Insulin
The development of insulin nanoparticles (NP) in addition to protecting insulin against a harmful gastric environment can avoid its enzymatic degradation, while controlling its release and enhancing its absorption in the small intestine.
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Abstract The development of insulin nanoparticles (NP) in addition to protecting insulin against a harmful gastric environment can avoid its enzymatic degradation, while controlling its release and enhancing its absorption in the small intestine. The enhancement of oral bioavailability of nanoencapsulated insulin has been demonstrated in animal studies. However, the question is why they were not followed by industrial development and clinical trials is still open. The variability of the insulin concentration delivered to the blood, the low bioavailability of encapsulated insulin requiring the administration of high doses and the lack of uptake mechanisms evidence, represent handicaps for the development of such delivery systems. Administration of such high doses of insulin transcellularly may induce mitogenic changes in the gastrointestinal epithelium, as insulin is a growth factor. Current NP systems must be improved both to increase the insulin loading and to lower the insulin dose required to produce a therapeutic glycemia reduction. Keywords Gastrointestinal epithelium • Insulin • Nanoparticle • Oral bioavailability • Therapeutic dose • Personalized medicine
A.J. Ribeiro () • F. Veiga Centre for Pharmaceutical Studies, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal e-mail: [email protected] R. Seiça Institute of Biomedical Research in Light and Image (IBILI), Faculty of Medicine, University of Coimbra, 3000-354 Coimbra, Portugal J. Coelho (ed.), Drug Delivery Systems: Advanced Technologies Potentially Applicable in Personalised Treatment, Advances in Predictive, Preventive and Personalised Medicine 4, DOI 10.1007/978-94-007-6010-3__4, © Springer ScienceCBusiness Media Dordrecht 2013
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1 Introduction Diabetes mellitus is a chronic disease that occurs either when the pancreas does not produce enough insulin and/or when the body became resistant to insulin actions. Diabetes and its complications have a significant economic impact on individuals, families, health systems and countries. For example, WHO estimates that 346 million people worldwide have diabetes and that deaths related to it will double between 2005 and 2030 [1]. Type 1 diabetes (previously known as insulindependent, juvenile or childhood-onset) is characterized by an almost complete loss of insulin mainly due to selective autoimmune destruction of the pancreatic “-cells and requires daily specific forms of diabetes. The etiology of type 1 diabetes is multifunctional and may involve genetic and environmental factors. Type 2 diabetes (formerly called non-insulin-dependent or adult-onset) results from insulin resistance and deterioration and “-cell function. Type 2 diabetes comprises 90% of people with diabetes around the world, and is largely related to excess body weight and physical inactivity. Gestational diabetes is hyperglycemia with onset or first recognition during pregnancy. Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are intermediate condit
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