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

作　　者：Yi Li Chao Teng Helena S.Azevedo Lifang Yin Wei He 

机构地区：[1]School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China [2]School of Engineering and Materials Science,Institute of Bioengineering,Queen Mary University of London,London E14NS,United Kingdom

出　　处：《Chinese Chemical Letters》2021年第10期3071-3075,共5页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81872823,81871477 and 82073782);the Double First-Class(CPU2018PZQ13,China)of the China Pharmaceutical University;the Shanghai Science and Technology Committee(No.19430741500);the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine,China(No.TCM-201905)。

摘　　要：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 antisolvent 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 rodshape 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 dosedependent pattern.In conclusion,by using a cocrystalization-like strategy,a hydrophilic drug can be formulated into a drug’s nanocrystal for codelivery.

关 键 词：Hybrid nanocrystal Codelivery Multidrug resistance PACLITAXEL Dichloroacetic acid COCRYSTALLIZATION 

分 类 号：TQ460.4[化学工程—制药化工]