Design and development of PLGA -hollow mesoporous silica nanoparticles for injectable micro- carriers of metformin based on a microfluidic device: Possible application for drug release in osteoarthritis treatment

• PLGA-HMSN microspheres ensure sustained, burst-free metformin release over 40 days. • Microfluidic synthesis enables monodisperse, size-controlled drug carriers (75.17 µm). • Drug release follows the Higuchi model, confirming diffusion-controlled mechanisms. • Encapsulation reduces toxicity, ensuring safety for normal chondrocyte cells up to 100 µM. • PLGA-HMSN microspheres show potential for osteoarthritis treatment with improved efficacy. Addressing the challenges of drug delivery in osteoarthritis (OA), this study explores a novel approach using Metformin (Met) encapsulated within poly(lactide-co-glycolide) (PLGA) microspheres containing hollow mesoporous silica nanoparticles (HMSN). By leveraging a flow-focusing microfluidic device, we designed and simulated the synthesis of injectable monodisperse PLGA-HMSN microspheres capable of sustained and burst-free drug release over 40 days. According to the cell viability test, the drug loaded in the microcarrier was much safer than the free drug, and the microcarriers were safe for normal chondrocyte cells up to a concentration of 100 micromoles. FTIR analysis confirmed successful Metformin loading into HMSNs and PLGA-HMSN microspheres. Structural analysis revealed nanoscale HMSNs averaging 279.23 nm and monodisperse PLGA-HMSN microspheres averaging 75.17 μm. The in vitro release profile of Met from HMSNs demonstrated a three-phase release: an initial burst (45 % in the first 10 h), a moderate release (60 % by 30 h), and a sustained release up to 80 h. In contrast, PLGA-HMSN microspheres showed a uniform, single-phase release without the initial burst, ensuring a linear release of Met over 40 days. The release kinetics aligned well with the Higuchi model, indicating a diffusion-controlled mechanism. These findings highlight that PLGA-HMSN microsphere synthesis with a microfluidic device provides a new promising strategy for precise, sustained Metformin delivery, offering significant improvements in OA treatment.