Tissue barriers and novel approaches to achieve hepatoselectivity of subcutaneously-injected insulin therapeutics

A Review on Bioengineering Approaches to Insulin Delivery: A Pharmaceutical and Engineering Perspective

“…It is clear that the injection route of insulin delivery is not able to provide enough concentration of insulin in the liver. Insulin–Tf has been proven to act as a liver targeted insulin to make a physiological balance in the peripheral and portal insulin concentrations . In the study by Shojaee et al., the administration of a covalently attached thyroxyl‐insulin to humans was reported for the first time.…”

“…Insulin-Tf has been proven to act as a liver targeted insulin to make a physiological balance in the peripheral and portal insulin concentrations. [44] In the study by Shojaee et al, the administration of a covalently attached thyroxyl-insulin to humans was reported for the first time. This bulky conjugate with a long serum half-life can only transfer through the open sinusoids in liver; however, it cannot pass endothelium and thereby have hepato-selectivity and provides a more physiological effect after subcutaneous injection in comparison to the NPH analog.…”

Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec

“…The activated ProINS-Tf exhibits a prolonged effect on the phosphorylation of Akt protein in H4IIE cells [ 2 ] and on the lowering of blood glucose levels in a type 1 diabetic mouse model under fasting conditions, where the liver plays a predominant role in controling blood glucose levels [ 1 , 2 , 3 ]. The liver has long been considered as the major organ in glucose homeostasis [ 4 ] and is the target organ of endogenous insulin action under physiological conditions [ 5 , 6 ]. Therefore, ProINS-Tf is considered an ideal insulin analog for the treatment of insulin-deficient diabetes due to its liver-targeted effects [ 5 , 6 ].…”

“…The liver has long been considered as the major organ in glucose homeostasis [ 4 ] and is the target organ of endogenous insulin action under physiological conditions [ 5 , 6 ]. Therefore, ProINS-Tf is considered an ideal insulin analog for the treatment of insulin-deficient diabetes due to its liver-targeted effects [ 5 , 6 ]. To further investigate the potential applications of ProINS-Tf in diabetes treatment, alternative expression systems were explored in this study aimed at achieving a high production yield for this recombinant fusion protein.…”

Introduction for the special issue on recent advances in drug delivery across tissue barriers

“…Finally, Shau et al 18 from the University of Southern California remind us that although sub-cutaneous (s.c.) insulin has been a life-saving drug for decades, there is still much that is poorly understood in relation to the interaction between peripheral insulin and its effects in the liver. The premise is that s.c-delivered insulin is actually quite poor at accessing the liver and that downside outcomes of peripherally-dosed insulin are an increased potential for hypoglycaemia excursion and weight gain.…”