Polypeptide-participating complex nanoparticles with improved salt-tolerance as excellent candidates for intelligent insulin delivery

Abstract

A facile strategy toward improving the salt-tolerance of a glucose-responsive delivery system to realize self-

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

“…Polymers. As reported, 47,49 the amphiphilic polymers, MPEG- S2). In the presence of HBr/HOAc, the benzyl protection groups were successfully removed from the PBLG blocks of P-4 (Scheme 1).…”

“…As reported, , the amphiphilic polymers, MPEG- b -PPBDEMA (P-1) and MPEG- b -PBLG (P-4) (Scheme ), were prepared by atom transfer radical polymerization (ATRP) and ring-opening polymerization (ROP) with MPEG-Br and MPEG-NH 2 as the macroinitiators, respectively. From the 1 H NMR results shown in Figure S1, the degree of polymerization (DP) of the PPBDEMA block in P-1 was calculated to be 75 by comparing the peak areas for the phenyl ring (δ = 7.78 ppm) of the PPBDEMA segment to that for the methyl group (δ = 3.43 ppm) of the MPEG block.…”

“…43−46 The coassembly of amphiphilic copolymers is one highly efficient and convenient method to obtain nanoparticles with the special properties of the individual copolymers. 47 Inspired by the higher ordered structures of synthetic polypeptides, we are curious whether simple changes in the secondary conformation of the nanocarriers via the coassembly of PBA-based polymers and amphiphilic polymers with polypeptide blocks will generate a great impact on the self-regulated response of the overall materials.…”

“…Diabetes is a chronic disease where the body is unable to regulate blood glucose level within the normal range. , Traditional administrations of exogenous insulin via subcutaneous injection and noninvasive therapy such as oral, nasal, transdermal, and ocular delivery systems cannot regulate insulin release continuously and automatically in response to the blood glucose fluctuation because the glucose-sensing and insulin-releasing modules are not directly integrated. , To resolve these issues for diabetic patients and reduce the incidence of hyperglycemia and hypoglycemia, smart therapies called closed-loop insulin release, which can precisely control the insulin amount on demand, have been broadly developed. − Among them, phenylboronic acid (PBA)-based glucose-triggered systems have attracted great interest because PBA and its derivatives can conjugate with glucose molecules to form a reversible ester bond for the achievement of the closed-loop effect. , Until now, a variety of PBA-based glucose-responsive materials, especially in the form of nanoparticles including nanogels (microgels), , micelles, − vesicles, − and nanocapsules, , have been broadly explored to improve their glucose concentration sensitivity and on–off regulated response in a physiological environment. Most of the PBA-based nanocarriers in the reported examples rely on the versatile architectural design of the glucose-responsive materials themselves to modulate the sensitivity of insulin release in response to blood glucose level changes. − The coassembly of amphiphilic copolymers is one highly efficient and convenient method to obtain nanoparticles with the special properties of the individual copolymers . Inspired by the higher ordered structures of synthetic polypeptides, we are curious whether simple changes in the secondary conformation of the nanocarriers via the coassembly of PBA-based polymers and amphiphilic polymers with polypeptide blocks will generate a great impact on the self-regulated response of the overall materials.…”

Thermo‐ and glucose‐sensitive microgels with improved salt tolerance for controlled insulin release in a physiological environment

“…Comparatively, PBA and its derivatives have been broadly studied as candidate materials for sensors and drug delivery systems for sugar‐regulated human diseases due to their versatility for different designs and better stability . Indeed, a variety of PBA‐based glucose‐responsive materials especially in the form of nanoparticles including micelles, vesicles and mesoporous silica nanoparticles have exhibited effective glucose sensitivity at physiological pH …”