Sodium cholesterol sulfate mediated mitoxantrone prodrug electrostatic nanocomplexes:achieving the therapeutic efficacy and safety of mitoxantrone  

作　　者：Erwei Zhao Lingxiao Li Jingyi Zhang Yaqiao Li Rong Chai Bowen Zhang Jialin Xing Minglong Huang Lurong Zhang Xiaohui Pu Zhonggui He Bingjun Sun 

机构地区：[1]Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Joint International Research Laboratory of Intelligent Drug Delivery Systems,Ministry of Education,Shenyang Pharmaceutical University,Shenyang 110016,China [3]Peking Union Pharmaceutical Factory Ltd.,Beijing 102600,China [4]State Key Laboratory of Antiviral Drugs,School of Pharmacy,Henan University,Kaifeng 475004,China [5]Department of Bioengineering,Graduate School of Engineering,The University of Tokyo,Tokyo 113-0033,Japan

出　　处：《Science China Chemistry》2025年第3期1185-1198,共14页中国科学(化学英文版)

基　　金：financial support from National Natural Science Foundation of China (82272151,82173766,and 82204318);Liaoning Revitalization Talents Program (XLYC2203083);Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program (RC220389)。

摘　　要：Forming electrostatic nanocomplexes(ENCs)with counter-ions can improve the delivery efficiency of chemotherapy drugs.However,water-soluble chemotherapy drugs like mitoxantrone(MTO),have limited affinity for counter-ions,posing challenges in the creation of stable ENCs.Herein,MTO was connected to fatty alcohols of varying chain lengths(C8,C12,C16)via disulfide bonds,forming hydrophobic prodrugs.We found that conjugating MTO to fatty alcohols significantly improved its affinity for the counter-ion sodium cholesterol sulfate(SCS).Among the designed prodrugs,conjugated to fatty alcohols with longer carbon chain lengths exhibited heightened affinity for SCS,resulting in the formation of more stable ENCs.However,extending the carbon chain also slowed the rate of drug release.Overall,compared with MTO solution,these ENCs demonstrated comparable therapeutic efficacy while causing minimal damage to healthy tissues,especially for MTO-SS-C16 ENCs.Our research provides new insights for constructing stable and safe ENCs for hydrophilic drugs like MTO.

关 键 词：MITOXANTRONE PRODRUG sodium cholesterol sulfate electrostatic nanocomplexes disulfide bond 

分 类 号：R91[医药卫生—药学] TB383.1[一般工业技术—材料科学与工程]