Cocrystallization-like strategy for the codelivery of hydrophobic and hydrophilic drugs in a single carrier material formulation

Codelivery of drugs by drug carriers is a promising strategy against several diseases such as infections and cancer. However, traditional drug carriers are typically characterized by low drug payload, limiting their treatment efficacy. Using nanocrystals of insoluble drug as carriers, a carrier free platform was developed previously to deliver a second insoluble drug for codelivery. To extend the concept, we hypothesized, herein, that the platform allows for codelivery of hydrophobic and hydrophilic drugs using a cocrystalization-like strategy. To obtain proof-of-concept, paclitaxel (PTX), an insoluble chemotherapeutic agent, and dichloroacetic acid (DCA), a water-soluble inhibitor of pyruvate dehydrogenase kinase, were utilized as model drugs. PTX-DCA hybrid nanocrystals (PTX-DCA NCs) were prepared by anti solvent precipitation and characterized. Their in vitro antitumor activity against cancer cells was evaluated. PTX-DCA NCs prepared from the optimized formulation had a diameter of 160 nm and a rod shape morphology and possessed encapsulated efficacy of approximately 30% for DCA. The use of the hybrid crystals enabled synergy to kill cancer cells, in particular in PTX-resistant cells in a dose dependent pattern. In conclusion, by using a cocrystalization-like strategy, a hydrophilic drug can be formulated into a drug's nanocrystal for codelivery. (c) 2021 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

Automated summary

Using nanocrystals as carriers, a cocrystalization-like strategy enables codelivery of hydrophobic and hydrophilic drugs. PTX-DCA hybrid nanocrystals showed synergistic antitumor activity against cancer cells, particularly in PTX-resistant cells.