New insights in nanocrystal technology chemotherapeutic drugs targeting cancer with a translational research paradigm.

Nanocrystal formulation has been increasingly investigated for overcoming the limitations of Biopharmaceutical Classification System (BCS) Class II and IV chemotherapeutic agents. Nanocrystal (NC) formation is widely accepted for increasing the solubility, biological barrier permeability, and cell internalization of poorly-soluble chemotherapeutic drugs. Nanocrystalization improves the bioavailability of anticancer agents, increasing their cytotoxicity and effectiveness for cancer treatment. NCs are nanodrug particles that are coated with a thin polymer or surfactant layer, that enhance their stability, solubility, and internalization in tumor cells. For active targeting, NCs can be decorated with ligands, e.g., proteins and amino acids. NCs also undergo passive targeting by high cellular uptake and retention in the mononuclear phagocyte system (MPS). They are prepared by either top-down, or bottom-up methods or a combination and can be scaled up for industrial manufacturing. NCs are safely administered by oral, parenteral, or transdermal routes. This review highlights the role of morphology and stabilizer, with brief discussions on nanocrystal production, ligand conjugation on drug nanocrystal targeting, and uptake in cancer cells. The benefits of NC formulations over conventional drug delivery are presented by discussing aspects of cytotoxicity studies of anticancer drugs.