Poly (lactic-co-glycolic acid) (PLGA) nanoparticles for sustained release of metformin hydrochloride within cells: A therapy for Type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is the third leading chronic disease threatening human health, with patients primarily managing their blood glucose levels through oral administration of metformin hydrochloride (MH). However, oral delivery of the pure drug faces challenges such as low bioavailability and significant gastrointestinal side effects. To address these, we employed a high-pressure homogenizer to prepare PLGA nanoparticles encapsulating the drug via a double emulsion method. Orthogonal experiments revealed that both shear pretreatment and high-pressure homogenization significantly influenced the particle properties, which were subsequently characterized. The average particle size could reach as small as 113.00 nm, with an encapsulation efficiency up to 64.69 %. The surface of these nanoparticles was negatively charged, enabling sustained drug release for 36 h in vitro. They exhibited excellent biocompatibility, maintaining a 95.74 % cell survival rate after 48 h of co-culture with hepatocytes, and were capable of being internalized by cells. In vivo experiments demonstrated that orally administered MH-PLGA nanoparticles could sustain blood glucose lowering effects for 8-10 h. Compared with traditional oral metformin hydrochloride, MH-PLGA nanoparticles offer higher bioavailability and lower gastrointestinal side effects, which are expected to bring better therapeutic effects to patients.