Citation: Yi Li, Chao Teng, Helena S. Azevedo, Lifang Yin, Wei He. Cocrystallization-like strategy for the codelivery of hydrophobic and hydrophilic drugs in a single carrier material formulation[J]. Chinese Chemical Letters, ;2021, 32(10): 3071-3075. doi: 10.1016/j.cclet.2021.03.085 shu

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

Yi Li ^{a, 1} ,
Chao Teng ^{a, 1} ,
Helena S. Azevedo ^b ,
Lifang Yin ^{a, *,} ,
Wei He ^{a, *,}

a.
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
b.
School of Engineering and Materials Science, Institute of Bioengineering, Queen Mary University of London, London E1 4NS, United Kingdom

lifangyin_@163.com

weihe@cpu.edu.cn

Received Date: 6 January 2021
Revised Date: 31 March 2021
Accepted Date: 1 April 2021
Available Online: 2 April 2021

Figures(4)

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.
- Hybrid nanocrystal,
- Codelivery,
- Multidrug resistance,
- Paclitaxel,
- Dichloroacetic acid,
- Cocrystallization
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