An injectable and glucose-sensitive nanogel for controlled insulin release

Abstract

Glucose-responsive polymer gels provide an attractive option for the design of a self-regulated insulin delivery system. Here, this paper reported the biocompatibility, glucose-sensitive behavior, and in vivo application of a dispersion of nanogels with three interpenetrating polymer networks of poly(Nisopropylacrylamide), dextran and poly(3-acrylamidophenylboronic acid) (P(NIPAM-Dex-PBA)). The nanogels had an average hydrodynamic radius of about 150 nm, and particle size increased with increasing content of dextran. The swelling behavior of the nanogels at different glucose concentrations revealed definite glucose sensitivity of P(NIPAM-Dex-PBA) particles. Furthermore, the analysis of relative cell proliferation suggested that the nanogels had good biocompatibility with L-929 mouse fibroblast cells. The loading amount of insulin, as a model drug, was up to 16.2%, and the drug release was dependent on the composition of dextran in the particles and the concentration of glucose present in release medium. In vivo experiments revealed that insulin-loaded nanogels decreased the blood glucose levels in diabetic rats and maintained 51% of the baseline level for almost 2 hours. The hypoglycemic effect of the drug-loaded nanogels was similar to that of free insulin after administration. Importantly, the drug-loaded nanogels could keep blood glucose levels stable and avoided blood sugar fluctuations compared with free insulin.

Biodegradable Polymer Nanogels for Drug/Nucleic Acid Delivery

“…182,183 For example, DEX-MA-BA-NIPAM NGs (90−210 nm) are prepared by radical polymerization of dextran methacrylate, 3-acrylamidophenylboronic acid (BA), and NIPAM, using N,Nmethylenebis(acrylamide) as cross-linker. These NGs have a glucose-sensitive swelling behavior.…”

Glucose- and temperature-sensitive nanoparticles for insulin delivery

“…Our results agree well with previously reported studies in this regard. 47,49,54 The insulin-loaded NPs and injection-treated groups have very similar glucose levels from 0 to 48 h after treatment, but after 48 h, the former showed an increase in blood glucose levels. This suggests that the NPs induce a stable hypoglycemic effect in the body over 48 h, but after this time, their efficacy is decreased.…”

“…The percentage release values observed and the release rates are broadly in agreement with the literature. [49][50][51] of these two materials (ie, had a lower LCST) and further, since AAPBA is very expensive, is more cost-effective than PAD-2-1. PAD-5-1 was thus taken forward into further work.…”

Recent advances in nanotechnology for diabetes treatment

“…The equilibrium between the two states is pushed towards the tetrahedral state in the presence of diols and polyols such as those found in glucose 58 . This equilibrium can be utilized to trigger the dissolution of amphiphilic nanocarriers and thus release insulin 59–63 . The equilibrium shift from the neutral to the charged form can also trigger the swelling of crosslinked hydrogel matrices.…”