Poloxamer-stabilized PLGA nanoparticles loaded with pterostilbene: Colloidal characterization and apoptosis-dominant cellular response in HepG2 cells

Polymeric nanoparticles (PNPs) represent tunable colloidal systems whose stability and interfacial properties govern their interactions in complex environments. In this study, pterostilbene (PTE)-loaded poly(lactic-co-glycolic acid) (PLGA) PNPs, stabilized with poloxamer 188 were formulated systematically evaluated with emphasis on time-dependent colloidal stability, surface-mediated interactions, and their implications for nano-biointerfaces. PNPs were prepared by an oil-in-water emulsion solvent evaporation method and optimized based on temporal evolution of average particle size (Z avg ), polydispersity index (PDI), and zeta potential (ζ). The optimized formulation exhibited a Z avg of approximately 131 nm, a narrow size distribution (PDI ∼ 0.13), a negative ζ (∼ −28 mV), and high drug entrapment efficiency (∼ 97%), indicating a well-dispersed colloidal system stabilized by a hydrated poloxamer corona. DLVO analysis suggested that electrostatic and steric interactions jointly stabilized the nanoparticles against aggregation. The optimized PNPs exhibited a biphasic drug release profile, with an initial burst release followed by sustained PTE release over 72 h. Transmission electron microscopy confirmed predominantly spheroidal nanoparticle morphology consistent with dynamic light scattering measurements. In vitro cytotoxicity assessment revealed a modest reduction in IC 50 for PTE-loaded PLGA PNPs compared with free PTE. Remarkably, flow cytometric analysis demonstrated a pronounced apoptosis-dominant cellular response (59%) and minimal necrosis. These findings highlight how surface-engineered electrostatic-steric stabilization governs colloidal stability and downstream nano-biointerfacial responses, underscoring the importance of colloidal interaction principles in the rational design of polymeric nanocarriers.