A Microstirring Oral Pill for Improving the Glucose-Lowering Effect of Metformin

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia due to persistent insulin resistance, resulting in elevated blood glucose levels. Metformin is the most prescribed oral drug for lowering high blood glucose levels in T2DM patients. However, it is poorly absorbed and has low bioavailability. Here, we introduce magnesium-based microstirrers to a metformin-containing pill matrix to enhance the glucose-lowering effect of metformin. The resulting microstirring pill possesses a built-in mixing capability by creating local fluid transport upon interacting with biological fluid to enable fast pill disintegration and drug release along with accelerated metformin delivery. In vivo glucose tolerance testing using a murine model demonstrates that the metformin microstirring pill significantly improves therapeutic efficacy, lowering blood glucose levels after a meal more rapidly compared to a regular metformin pill without active stirring. As a result, the microstirrers allow for dose sparing, providing effective therapeutic efficacy at a lower drug dosage than passive metformin pills. These encouraging results highlight the versatility of this simple yet elegant microstirring pill technology, which enhances drug absorption after gastrointestinal delivery to improve therapeutic efficacy.

Recent advancements in Mg-based micromotors for biomedical and environmental applications

“…Experimental results show that the rate of reduction in the postprandial blood sugar levels realized by using self-stirring metformin tablets was higher than that achieved via the traditional delivery of metformin. 64 To improve the resistance of oral insulin to the harsh digestive environment, Liu, Peng, and Tu et al proposed the oral delivery of insulin system via tablets of insulin-loaded Mg micromotors and auxiliary materials with subsequent esterified by starch encapsulation; by using these tablets, blood sugar control for more than 5 h was realized. 26 To increase the speed of micromotors and enhance the penetration of micromotors into the gastrointestinal mucous membrane of organisms, Maric et al proposed a cascading device that nested Mg-based Janus micromotors in a microcontainer for drug loading and transportation.…”

“…63 Subsequently, to improve the bioavailability and reduce the blood sugar levels of patients with diabetes, a similar method was used to prepare self-stirring tablets loaded with metformin. 64 Liu, Peng, and Tu et al adopted the hydrophobic modification of natural starch by acetic anhydride, washed and removed pyridine and unreacted acetic anhydride to obtain esterified starch, and then dried and pulverized the esterified starch; then, they prepared insulin-loaded Mg/Au-CHI Janus micromotors by bottom-up deposition and coating with a Mg monolayer. Finally, esterified starch and micromotors were mixed and then pressed into tablets (Fig.…”

“…26,69 Wang and Zhang et al studied the speed of micromotors in simulated gastric and simulated intestinal fluids, and the speed of the micromotors was as high as 350 mm s À1 in simulated gastric fluid with a low pH and decreased to 180 mm s À1 in simulated intestinal fluid with higher pH. 64 However, the control of the direction of micromotors is difficult: a single-drive can no longer propel the micromotor to complete complicated tasks. To control the motility of micromotors, field-controlled particles were induced based on chemically driven micromotors.…”

“…63 Subsequently, to improve the bioavailability and reduce the blood sugar levels of patients with diabetes, a similar method was used to prepare self-stirring tablets loaded with metformin. 64…”

“…For example, when the concentration of NaCl in the medium was increased from 0.3 M to 3 M, the speed of micromotors could be increased from 90 μm s −1 to 300 μm s −1 . 45 To further stabilize the generated bubbles in order to improve the driving efficiency, a minority surfactant, such as SDS, 31 Triton X-100, 64 and Tween-20, 22 is added to the reaction medium. Finally, thermal energy can also improve the motion of micromotors: as the temperature rises, the rate of bubble generation increases, thus increasing the speed of the micromotors.…”