A Novel Drug Delivery System: Hyodeoxycholic Acid-Modified Metformin Liposomes for Type 2 Diabetes Treatment

Abstract

Metformin is a first-line drug for the clinical treatment of type 2 diabetes; however, it always leads to gastrointestinal tolerance, low bioavailability, short half-life, etc. Liposome acts as an excellent delivery system that could reduce drug side effects and promote bioavailability. Hyodeoxycholic acid, a cholesterol-like structure, can regulate glucose homeostasis and reduce the blood glucose levels. As an anti-diabetic active ingredient, hyodeoxycholic acid modifies liposomes to make it overcome the disadvantages of metformin as well as enhance the hypoglycemic effect. By adapting the thin-film dispersion method, three types of liposomes with different proportions of hyodeoxycholic acid and metformin were prepared (HDCA:ME-(0.5:1)-Lips, HDCA:ME-(1:1)-Lips, and HDCA:ME-(2:1)-Lips). Further, the liposomes were characterized, and the anti-type 2 diabetes activity of liposomes was evaluated. The results from this study indicated that three types of liposomes exhibited different characteristics—Excessive hyodeoxycholic acid decreased encapsulation efficiency and drug loading. In the in vivo experiments, liposomes could reduce the fasting blood glucose levels, improve glucose tolerance, regulate oxidative stress markers and protect liver tissue in type 2 diabetic mice. These results indicated that HDCA:ME-(1:1)-Lips was the most effective among the three types of liposomes prepared and showed better effects than metformin. Hyodeoxycholic acid can enhance the hypoglycemic effect of metformin and play a suitable role as an excipient in the liposome.

Advances in metformin‐delivery systems for diabetes and obesity management

“…It employs new technologies, ideas, and methodologies to address the limitations of conventional drug‐delivery systems, including limited bioavailability, inconsistent plasma drug levels, and the inability to provide sustained release 59–61 . Innovative pharmaceutical approaches, such as fast‐dissolving tablets with the optimized dosage formulation, 62–68 micro and nanoparticle formulations, 17,69–95 micro and nanofabricated devices, 48,49,96–102 and other delivery systems, such as hydrogels, 103,104 membranes 105 and film dressing, 106 have been investigated to optimize metformin efficacy, dosage, targeting, bioavailability, and compliance 107 . Figure 1 compares conventional and novel delivery systems for metformin, highlighting the advancements in drug‐delivery technology to improve drug efficacy, patient compliance, and therapeutic outcomes.…”