Heliotropium crispum-mediated assembly of silver nanoparticles exhibit profound antibacterial and anti-biofilm effects against multiple drug-resistant bacteria, but its stability and biocompatibility remain a hurdle in commercialization. Herein, we adopted a surface chemistry-based steric repulsion approach to investigate the colloidal stability of H. crispum silver nanoparticles (HC-AgNPs) and determine its application as a commercial antibacterial formulation. Two primary silver nanoparticles (AgNPs) were synthesized, i.e., HC-AgNPs and citrate-HC-AgNPs initially, which were then modulated to assemble various derivatives of AgNPs using polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP) as stabilizing agents. Various parameters were assessed to investigate the morphology, colloidal physio-chemistry, and surface capping using various analytical techniques, such as UV–Vis spectrophotometer, zeta–dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM, and transmission electron microscopy (TEM). Selective AgNPs were then screened on the basis of stability for up to 8 months, heat resistance at 100 °C, and bioactivity via MTT assay using HEP-2, MCF-7, and HCEC cell lines. The UV–Vis and electron microscope results revealed that HC-AgNPs confer near-spherical and slight triangular-shaped morphology and the size of all synthesized AgNPs is in the range of 400–450 nm. All AgNPs synthesized from HC-source have characteristic FTIR peaks recorded near 2931 cm−1, 1996 cm−1, and 825 cm−1. This study highlights promising evidence for the commercial application of HC-AgNPs as an antimicrobial agent. Additionally, it provides a methodology for modulating the surface capping of biological nanoparticles and assesses its corresponding effect on the stability.
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