Abstract
<title>Abstract</title> <p>Drug delivery systems powered by nanotechnology have greatly progressed pharmaceutical science by enhancing the solubility, stability, and therapeutic effectiveness of bioactive compounds. In this study, lipid–polymeric hybrid nanoparticles (LPHNPs) containing Phlorizin were created through a one-step nanoprecipitation method to address the compound's natural limitations in solubility and bioavailability. Thorough characterization was conducted, encompassing evaluations of particle size, zeta potential, morphology, entrapment efficiency, and in vitro drug release profile. Dynamic light scattering assessments revealed a Z-average particle size of 425.7 nm and a polydispersity index (PDI) of 0.272, showing consistency in size distribution. The nanoparticles showed a zeta potential of − 28.8 mV, suggesting strong colloidal stability. Scanning electron microscopy showed clearly defined, solid nanoparticles at the nanoscale. The formulation reached an entrapment efficiency of 99.62% and exhibited prolonged drug release for as long as 20 hours, adhering to near-zero-order kinetics. The anti-senescence effect was assessed in high glucose-exposed 3T3-L1 murine adipocytes through the use of SA-β-Gal staining. The Phlorizin nanosuspension offered dose-dependent defense against cellular senescence, demonstrated by a decrease in SA-β-Gal-positive cells at higher concentrations. Morphological assessment verified the return to a typical fibroblast-like cell structure. Together, these findings suggest that Phlorizin-loaded LPHNPs have significant potential as a nanocarrier system to improve therapeutic delivery and reduce glucose-triggered adipocyte senescence.</p>