Development of glucose oxidase-immobilized alginate nanoparticles for enhanced glucose-triggered insulin delivery in diabetic mice.

In this work, we successfully developed poly(acrylamido phenylboronic acid)/sodium alginate nanoparticles (NPs) via formation of cycloborates (glucose- and H2O2-responsive functional groups), as an improved glucose-mediated insulin delivery system loaded with glucose oxidase (GOx). Dynamic light scattering revealed that the GOx-loaded NPs showed better glucose-sensitivity than the GOx-unloaded NPs. In addition, compared to insulin-loaded NPs, the insulin/GOx-loaded NPs displayed faster glucose-responsive insulin release. Importantly, there was a significant hypoglycemic effect on diabetic mice following the subcutaneous injection of insulin/GOx-loaded NPs. Furthermore, the NPs exhibited favorable biocompatibility as demonstrated by cytotoxicity assay, hemolysis study, and histopathological examination. The NPs have the advantages of easy preparation, enhanced glucose-responsiveness, and good biocompatibility, making them as potential candidates for subcutaneous insulin delivery.

Chai Z ，Dong H ，Sun X ，Fan Y ，Wang Y ，Huang F ... -  《-》

pH and H(2)O(2) dual-sensitive nanoparticles enable enhanced and safe glucose-responsive oral insulin delivery for diabetes mellitus treatment.

Li M ，Wang N ，Liu R ，Zhang X ，He W ，Zhang W ，Li J ，Peng C ，Li Y ... -  《Theranostics》

Glucose and H(2)O(2) dual-sensitive nanogels for enhanced glucose-responsive insulin delivery.

Li C ，Liu X ，Liu Y ，Huang F ，Wu G ，Liu Y ，Zhang Z ，Ding Y ，Lv J ，Ma R ，An Y ，Shi L ... -  《-》

Glycopolypeptide Nanocarriers Based on Dynamic Covalent Bonds for Glucose Dual-Responsiveness and Self-Regulated Release of Insulin in Diabetic Rats.

Wang Y ，Fan Y ，Zhang M ，Zhou W ，Chai Z ，Wang H ，Sun C ，Huang F ... -  《-》

Preparation, in vitro and in vivo evaluation of PLGA/Chitosan based nano-complex as a novel insulin delivery formulation.

The smart self-regulated drug delivery systems for insulin administration are desirable to achieve glycemic control, and decrease the long-term micro- and macro vascular complications. In this study, we developed an injectable nano-complex formulation for closed-loop insulin delivery after subcutaneous administration and release of insulin in response to increased blood glucose levels. The nano-complex was prepared by mixing oppositely charged chitosan and PLGA nanoparticles. PLGA nanoparticles were prepared using double-emulsion solvent diffusion method, and were loaded with glucose oxidase (GOx) and catalase (CAT) enzymes. These negatively charged particles decrease micro-environmental pH, by gluconic acid production in the glucose molecules presence. Positively charged chitosan nanoparticles were prepared using ionic gelation method, and were loaded with insulin. These nanoparticles (NPs) released insulin by dissociation in acidic pH caused by the GOx activity. Following in vitro studies, in vivo evaluation of nano-complex formulations in streptozocin induced diabetic rats showed significant glycemic regulation up to 98 h after subcutaneous administration.

Mohammadpour F ，Hadizadeh F ，Tafaghodi M ，Sadri K ，Mohammadpour AH ，Kalani MR ，Gholami L ，Mahmoudi A ，Chamani J ... -  《-》