Nitrilotriacetic Acid (NTA) and Phenylboronic Acid (PBA) Functionalized Nanogels for Efficient Encapsulation and Controlled Release of Insulin

Protein drugs play a significant role in the treatment of many diseases such as diabetes, cancers, and immune system diseases. Though polymeric nanocarriers have been designed to deliver protein drugs for prolonging circulation lifetime and providing stimuli-triggered release, problems are still often encountered including lower loading efficiency and capacity as well as poor circulation stability because of the weak interaction between protein drugs and nanocarriers. Herein, we described a new kind of bifunctional polymeric nanogels for efficient loading and glucose-triggered release of insulin. Biodegradable poly(N-isopropylacrylamide) (PNIPAM)-based nanogels was synthesized with nitrilotriacetic acid (NTA) and phenylboronic acid (PBA) as functional groups and ethylene glycol dimethacrylate (EGDMA) as cross-linker. The NTA groups could specifically bind imidazole-containing protein drugs such as insulin via chelated zinc ions, leading an efficient loading of insulin. The structure, morphology, and drug-loading properties of the nanogels were well-characterized, and glucose-triggered insulin release was achieved based on the glucose-responsiveness of PBA groups. MTT assay and enzymatic degradation revealed good biocompatibility and biodegradability for the nanogels. This kind of bifunctional nanogels would be promising candidates for glucose-responsive delivery of insulin in the future.