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

Abstract

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.

Insulin Delivery Using Dynamic Covalent Boronic Acid/Ester‐Controlled Release

“…Under normoglycemic conditions (5.5 × 10 −3 m glucose) ≈20% cumulative release of loaded insulin occurred after 90 h, while significant increases in insulin re- (P-3) reported by Yang and co-workers. [151] lease were observed under elevated glucose concentrations (11.1 × 10 −3 and 16.6 × 10 −3 m) under the same conditions at the same time (≈75% and 90% cumulative loaded insulin release, respectively). The two other materials displayed inferior properties, in terms of both salt stability and insulin release discrimination for different glucose concentrations, attributed by the authors to the differences of secondary structures of polyamide components of the assemblies.…”

“…Yang and co‐workers further explored their glucose responsive platform for insulin delivery in context of how the polyamide component's secondary structure influenced the payload discharge process. [ 151 ] The authors prepared equivalent sets of two block copolymers, with higher degrees of polymerisation in poly(γ‐benzyl‐ l ‐glutamate) block. Next, partial hydrolysis of benzyl esters was performed yielding two derivatives with ester to carboxylic acid ratios of 20:40 and 48:12 ( Figure ).…”

“…The structure of block copolymers MPEG‐ b ‐PPBDEMA (P‐1) , MPEG‐ b ‐PBLG (P‐4) , MPEG‐ b ‐(PBLG‐ co PGA) (P‐2) , and MPEG‐ b ‐(PBLG‐ co PGA) (P‐3) reported by Yang and co‐workers. [ 151 ] …”