Delivering anticancer drugs as carrier-free nanocrystals

Chemotherapy has remained a first-line option for treating various types of cancers. Yet, many anticancer compounds cannot freely dissolve in aqueous environments, presenting great challenges in drug delivery. To enhance the dissolution rate and enable in vivo absorption in targeted tissues, these poorly soluble drugs are often formulated with solubilizing chemicals and solvents. Unfortunately, these methods often induce detrimental side effects because of ubiquitous exposure in the body and the inherent, unwanted cytotoxicity of these chemicals and solvents. The current formulation approaches of encapsulation and solubilization are also subjected to manufacturing difficulties and stability issues. Drug nanocrystals (NCs), on the other hand, represent a drastically different concept of delivering chemotherapeutic compounds without using solubilizing carrier substances. Directly injected as solid particles, the NC formulation can lead to enhanced dissolution, improved absorption and bioavailability, elimination of side effects from carrier chemicals, and enhanced efficacy. Moreover, this carrier-free delivery can reach 100% drug loading; even when surfactants are needed to stabilize NCs in solution, the drug loading can still be >90%. Generation of NCs mostly involves physical processes of comminution or crystallization, offering scale-up flexibility toward commercial production. In this report, we highlight three aspects associated with drug NCs—production, cellular interaction, and in vivo performance against tumors—to demonstrate that intravenously delivering a drug as submicron solid particles is a viable option for chemotherapy.