Cocrystallization-like strategy for the codelivery of hydrophobic and hydrophilic drugs in a single carrier material-free formulation
2021
Abstract Codelivery of drugs is a promising strategy against several diseases such as infections and cancer. However, traditional drug carriers are typically characterized by having low drug payload limiting their long-term treatment efficacy. Using nanocrystals of insoluble drug as carriers, a carrier material-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 in a drug’s nanocrystals for codelivery.
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