Synthesis and performance optimization of multi-bioactive compound-loaded nanocarriers for antimicrobial applications

Curcumin (Cur), quercetin (Que), and piperine (Pip) are well-known plant-derived compounds with diverse pharmacological activities and health benefits. However, their clinical application is limited due to hydrophobicity and poor bioavailability. Polylactic-co-glycolic acid nanoparticles(PLGA NPs) provide efficient drug loading and sustained release, making them an ideal platform for controlled drug delivery. Cur, Que, and Pip co-loaded PLGA NPs (Cur-Que-Pip-PLGA NPs) were prepared using the emulsification-solvent evaporation method. Their physicochemical properties were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS),and high-performance liquid chromatography (HPLC). Biocompatibility was assessed through the CCK-8 cytotoxicity assay and Calcein AM/PI cell viability staining. Antimicrobial activity was investigated via the agar diffusion method. The average particle size of Cur-Que-Pip-PLGA NPs was 210.6 ± 0.22 nm, with a zeta potential of -8.57 ± 1.16 mV and a polydispersity index (PDI) of 0.186 ± 0.010. The encapsulation efficiencies of Cur, Que, and Pip were 97.1%, 95.5%, and 45.5%, respectively. The NPs were spherical with smooth surfaces. In vitro studies revealed that the cumulative release of Cur-Que-Pip-PLGA NPs in PBS after 96 h of sustained release was 26.9%, 57.5%, and 98%, respectively. In contrast, the cumulative release of free Cur, Que, and Pip after only 8 h of sustained release reached 92.1%, 94.8%, and 96.6%, respectively. This comparison highlights the significant slow-release effect of PLGA NPs. The NPs exhibited excellent stability at 25 ± 3°C for 14 days. The results of the CCK-8 cytotoxicity assay and Calcein AM/PI cell death staining indicated that Cur-Que-Pip-PLGA NPs exhibited good biocompatibility with RAW264.7, BMSC, and MC3T3 cells, with no significant cytotoxic effects. Agar diffusion method confirmed its good antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Cur-Que-Pip-PLGA NPs demonstrate excellent biocompatibility, controlled release, and antimicrobial properties, suggesting potential for improving the therapeutic performance of hydrophobic compounds.