Impact of Secondary Structure of Polypeptides on Glucose Concentration Sensitivity of Nanocarriers for Insulin Delivery

A reasonably intelligent response to glucose concentration fluctuations is crucial for developing a self-regulated insulin delivery system. Inspired by the relationship between the higher ordered structures of proteins and their versatile functions, the introduction of polypeptides capable of mimicking different secondary structures into the delivery system will be anticipated for adjusting glucose concentration sensitivity. Herein, this work presents the impact of different secondary structural architectures of polypeptide blocks on the stability of glucose-responsive complex nanoparticles (CNPs) in the normal physiological environment and their response to the stimuli of normoglycemic and hyperglycemic conditions in vitro. Results from the conformational investigations of the CNPs carried out using circular dichroism and insulin release under the different stimuli suggested that the stability and glucose sensitivity of the CNPs are closely related to the secondary structure composition of the polypeptide blocks. The CNPs with a dominant α-helix structure exhibit a promising potential to improve normal glycemic control and to reduce the incidences of hyperglycemia and hypoglycemia both in vitro and in vivo