A Nanocrystal Platform Based on Metal-Phenolic Network Wrapping for Drug Solubilization

The preparation of drugs into nanocrystals represents a practical pharmaceutical technology to solubilize poorly water-soluble drugs and enhance bioavailability. However, commonly used stabilizers in nanocrystals like polymers and surfactants are frequently inefficient and cannot stabilize nanocrystals for an expected time. This study reports an exquisite platform for nanocrystal production based on a metal-phenolic network (MPN). MPN-wrapped nanocrystal particles (MPN-NPs) were fabricated through an anti-solvent precipitation method using tannic acid and Fe^III or Al^III as coupling agents and characterized by dynamic light scattering, transmission electron microscope, ultraviolet and visible spectrophotometry, fourier-transform infrared spectroscopy, and X-ray powder diffraction. In vitro release, cytotoxicity, and stability were mainly studied with MPN-NPs loading paclitaxel. The suitability of MPN as a nanocrystal stabilizer was also investigated for other classical hydrophobic drugs, including simvastatin, andrographolide, atorvastatin calcium, ferulic acid, and famotidine. The results showed that MPN could effectively wrap and stabilize various drug nanocrystals apart from famotidine. The maximum solubilization of MPN towards atorvastatin calcium was up to 1587 folds, and it also exhibited an excellent solubilizing effect on other hydrophobic drugs. We disclosed that the drug was entrapped in MPN in the nanocrystal form, and there were distinct physiochemical interactions between MPN and the payload. Our findings suggested that MPN may be a promising platform for nanocrystal production to address the challenge of low solubility associated with hydrophobic drugs. Graphical abstract.