Overcoming hurdles in nano-phytochemical development: challenges and future directions.

The clinical applications of phytochemicals are limited due to challenges such as poor tissue distribution, low solubility in bodily fluids, low absorption, off-target toxicity, and low efficacy. Advances in nanomedicine have offered opportunities to overcome these limitations by incorporating phytochemicals into various organic and inorganic nanocarriers. Despite this progress, nano-phytochemical formulations still face numerous obstacles. Today, nano-phytochemical research is focused on issues such as solubility, stability, and bioavailability. Active targeting remains particularly challenging due to the difficulty of identifying suitable ligands for complex molecules like phytochemicals. Efforts are underway to discover cancer-specific ligands capable of directing nano-phytochemicals toward tumors. Additionally, standardized construction techniques and robust monitoring processes are essential to facilitate the translation of nano-phytochemicals from nano-scale to large-scale production. Finally, despite the growing number of nano-phytochemical formulations in the preclinical stage, many of these fail to reach clinical trials, partly due to safety concerns. Expanding our understanding of the toxicity of nano-phytochemicals, especially potential long-term adverse effects, is critical for advancing their clinical applicability.