Zenli ChengAshok Kumar JanakiramanRamkanth SundarapandianSinouvassane DjearamaneHanish Singh Jayasingh ChellammalHaja Nazeer AhamedSaminathan Kayarohanam2025-10-242025-10-242025-0510.1016/j.nanoso.2025.101472https://dspace-cris.utar.edu.my/handle/123456789/11571The application of multifunctional zinc oxide nanoparticles (ZnONPs) for the delivery of vinblastine (VB) represents a novel approach in nanomedicine. However, the synthesis of this combination, its characteristics and potential in biomedical applications have yet to be explored. Given its promising therapeutic prospects, a holistic experimental approach is essential to achieve a robust formulation of VB-ZnONPs with therapeutic values. Hence, this study aimed to employ statistical experimental design to optimize the synthesis of vinblastine (VB)-loaded ZnONPs and assess their potential in targeted drug delivery and antimicrobial applications. The effect of the critical process parameters such as stirring temperature, stirring speed and drying temperature on the mean particle size, zeta potential (ZP), and entrapment efficiency (EE) were evaluated and the optimal synthesis conditions were determined with Box-Behnken Design (BBD). Under the optimal synthesis conditions, VB-ZnONPs achieved mean particle size, ZP and EE of 159 ± 0.78 nm, −16.5 ± 0.61 mV and 92.8 ± 0.02 %, respectively, consistent with the predicted values from the software. UV–visible spectroscopy revealed an absorbance peak at 270 nm for VB and 344 nm for ZnONPs, confirming the formation of VB-ZnONPs. Further, the synthesis of VB-ZnONPs was affirmed through the detection of VB and ZnO functional groups in the Fourier transform infrared spectroscopy. Transmission electron microscopy confirmed irregular and quasi-spherical shaped particles, while energy-dispersive X-ray spectroscopy (EDX) displayed the elemental distribution of zinc, oxygen and carbon. The stability of VB-ZnONPs was verified through thermogravimetric analysis. X-ray diffraction pattern revealed that VB-ZnONPs possessed a crystallite size of 22.9 nm and a hexagonal wurtzite structure. VB-ZnONPs demonstrated pH-sensitive release of VB, indicating potential for targeted delivery to tumor microenvironment. Moreover, they prevented the growth of Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) in a dose-dependent manner. These research findings underscore the significance of employing a statistical approach in optimizing the formulation of VB-ZnONPs and the potential of VB-ZnONPs in biomedical applications. © 2025 Elsevier B.V.enAntibacterialCritical process parametersFormulation optimizationStatistical experimental designVinblastine sulfateZinc oxide nanoparticlesjournal-article