Glucose and pH Dual‐Responsive Nanogels for Efficient Protein Delivery

Abstract

Direct delivery of protein suffers from their in vitro and in vivo instability, immunogenicity, and a relatively short half‐life within the body. To overcome these challenges, pH and glucose dual‐responsive biodegradable nanogels comprised of dextran and poly(L‐glutamic acid)‐g‐methoxy poly‐(ethylene glycol)/phenyl boronic acid (PLG‐g‐mPEG/PBA) are designed. The cross‐linked network imparted drug‐loading efficacy of α‐amylase up to 55.6% and hyaluronidase up to 29.1%. In vitro protein release profiles reveal that the release of protein is highly dependent on the pH or glucose concentrations, that is, less amount of protein is released at pH 7.4 or healthy blood glucose level (1 mg mL−1 glucose), while quicker release of protein occurs at pH 5.5 or diabetic blood glucose level (above 3 mg mL−1 glucose). Circular dichroism spectra show that the secondary structure of released protein is maintained compared to naive protein. Overall, the nanogels have provided a simple and effective strategy to deliver protein.

Novel glucose-responsive nanoparticles based on p-hydroxyphenethyl anisate and 3-acrylamidophenylboronic acid reduce blood glucose and ameliorate diabetic nephropathy

“…The distributions of AAPBA and p(AAPBA) spectra are consistent with that of Li et al. [ 25 , 26 ]. In addition, compared with AAPBA and HPA, the p(AAPBA-b-HPA)2 polymer has a characteristic monomer peak, a peak of the corresponding C C double bond disappears, and a peak of H at a position where the main chain appears, which confirm the occurrence of a polymerisation reaction.…”

Versatile Oral Insulin Delivery Nanosystems: From Materials to Nanostructures

“…The hypoglycemic effect was verified in animal experiments. Si et al developed a novel nanogel system with a particle size of approximately 44 nm based on poly (L-glutamic acid)- g -methoxypoly (ethylene glycol)/aminophenylboronic acid (PLG- g -mPEG/PBA) and dextran ( Figure 7 C) [ 133 ]. The nanogel was constructed through the reversible reaction of boron ester bonds between cis -diol on dextran and phenylboronic acid in PLG- g -mPEG/PBA, and insulin was loaded into the cross-linked lattice during the formation process.…”

Development of a Polysaccharide-Based Hydrogel Drug Delivery System (DDS): An Update

“…The nanogels (CytoC/aNGs) increased the cellular uptake of cytochrome c and improved the intracellular delivery to the targeted sites to induce apoptosis [82]. In another study, pH and glucose dual-responsive biodegradable nanogels were constructed and showed the release of the encapsulated proteins [83]. These nanogels were highly dependent on glucose or pH concentrations, where low amounts of proteins were released in physiological pH or under healthy blood glucose level, while the rapid release was seen at lower pH or under diabetic blood glucose level [83].…”

“…In another study, pH and glucose dual-responsive biodegradable nanogels were constructed and showed the release of the encapsulated proteins [83]. These nanogels were highly dependent on glucose or pH concentrations, where low amounts of proteins were released in physiological pH or under healthy blood glucose level, while the rapid release was seen at lower pH or under diabetic blood glucose level [83]. Massi et al generated a temperature-sensitive nanogel that responded to matrix metalloproteinase-7 (MMP-7) and with the addition of N-cyclopropylacrylamide (NCPAM) into NIPAM-based copolymer, it allowed the encapsulation of protein cargo and nanogel-crosslinking at slightly elevated temperatures [84].…”