Safety Validation of Nano-Herbal Formulations: A Systematic Review

Abstract

Nano-herbal formulations hold significant therapeutic promise, yet their clinical translation is hindered by an insufficient link between physicochemical characterization and biological safety outcomes. This systematic review establishes a correlative framework that integrates X-ray diffraction (XRD), scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDX), and Fourier-transform infrared spectroscopy (FTIR) to validate the safety of these formulations. A structured data extraction template captured study identity, formulation type, XRD-derived crystallinity metrics, SEM-EDX morphology and elemental composition, FTIR surface chemistry, synthesis parameters, and safety endpoints such as half-maximal inhibitory concentration (IC50) and reactive oxygen species (ROS) fold-change. The review yielded a comprehensive dataset predominantly for green-synthesized silver and zinc oxide nanoparticles. Our analysis demonstrates that a correlative XRD-SEM-EDX-FTIR framework is feasible and widely applied, but the retrieved studies primarily support qualitative characterization rather. For instance, Rubus discolor leaf extract-mediated silver nanoparticles exhibited crystalline XRD patterns, a strong silver peak in EDX, and FTIR evidence of phenolic capping, with IC50 values ranging from 11 to 49.1 micrograms per milliliter across multiple cancer cell lines. Encapsulated formulations showed reduced crystallinity or an amorphous halo in XRD, homogeneous elemental distribution in EDX, and attenuated payload bands in FTIR, correlating with a more favorable safety profile. A tentative safety hierarchy positions encapsulated systems as most likely to reduce immediate bioactive exposure, followed by surface-adsorbed systems. However, no retrieved study simultaneously reported explicit interaction-mode classification, full XRD crystallinity metrics, SEM-EDX elemental mapping, and quantitative biocompatibility endpoints, future studies must report these descriptors concurrently to enable robust safety prediction and reduce reliance on extensive biological testing during early development.