Sustained Glipizide Release and Enhanced Hypoglycemia With Nano-Mesoporous SBA-15 in Diabetic Mice

Glipizide is an oral hypoglycemic medication that has many limitations in its therapeutic use due to poor aqueous solubility and low plasma half-life. These disadvantages result in inefficient glycemic regulation and a high frequency of dosing. To develop and test different mesoporous silica nanocarriers (MSN), especially Santa Barbara Amorphous-15 (SBA-15), to deliver glipizide continuously and enhance the overall therapeutic effects on diabetic mice. Nano-mesoporous carriers (Mobil Composition of Matter No. 41 [MCM-41], SBA-15, and Hollow Mesoporous Nanoparticles [HMNs]) were synthesized and loaded with glipizide. After assessing drug encapsulation efficiency, SBA-15 was selected as the model for our study. SBA-15 and SBA-15 with surface-modified amine groups were characterized using zeta potential, Fourier-transform infrared spectroscopy (FTIR), scanning microscopy (SEM), and X-ray diffraction (XRD). In vivo evaluation of SBA-15 loaded with glipizide was conducted using streptozotocin-induced diabetic mice to measure glucose and insulin levels. Glipizide entrapment was highest in SBA-15 compared to other nano-mesoporous carriers. The high surface area, large pore diameter, and uniform morphology were confirmed by characterization, which facilitates efficient loading of drugs and stable amorphous dispersion of glipizide. In vitro dissolution revealed that there was a high pH dependence: at gastric pH (1.0), SBA-15/glipizide released approximately 25% at 2 h, and with further release thereafter, whilst at intestinal pH (7.4) it released approximately 90% at 2 h, and sustained release thereafter. Furthermore, the study on streptozotocin-induced diabetic mice showed that SBA-15 loaded with glipizide significantly reduced glucose levels and enhanced insulin release over 48 h compared to glipizide alone. SBA-15 is a viable nanocarrier of glipizide that offers high encapsulation efficiency, good physicochemical characteristics, and long-term pH-dependent release, resulting in long-term therapy. This intervention has the potential to improve diabetes management and patient adherence.