A liposomal etoposide with a sustained drug release effectively alleviated the therapy-related leukemia

作者全名："Xiong, Yan; Xie, Lei; Tang, Lingfeng; Xiao, Danling; Shi, Wenhao; Wang, Yang; Li, Yang; Han, Xue; Ying, Xue; Zheng, Yaxin"

作者地址："[Xie, Lei; Xiao, Danling; Shi, Wenhao; Han, Xue; Ying, Xue; Zheng, Yaxin] Chengdu Med Coll, Sch Pharm, Key Lab Sichuan Prov Specif Struct Small Mol Drugs, Chengdu, Peoples R China; [Xiong, Yan] Chengdu Med Coll, Affiliated Hosp 2, China Natl Nucl Corp 416 Hosp, Chengdu, Peoples R China; [Li, Yang] Chongqing Med Univ, Coll Pharm, Dept Pharmaceut, Chongqing 400016, Peoples R China"

通信作者："Han, X; Ying, X; Zheng, YX (通讯作者)，Chengdu Med Coll, Sch Pharm, Key Lab Sichuan Prov Specif Struct Small Mol Drugs, Chengdu, Peoples R China."

来源：INTERNATIONAL JOURNAL OF PHARMACEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001097546700001

JCR分区：Q1

影响因子：5.8

年份：2023

卷号：646

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Etoposide; Liposomes; Toxicity; Antitumor activity; Lymphocytosis; Sustained drug release

摘要："Etoposide (VP16) can induce therapy-related leukemia, which is reported to occur less frequently with a pro-longed dose schedule. Therefore, we hypothesized that nanocarriers could decrease the VP16-induced leuke-mogenesis by reducing the rate of VP16 exposure via a sustained drug release. To test our hypothesis, the VP16-loaded liposome with a slow drug release behavior was constructed by encapsulating a rapidly-cleaved VP16-maleimide conjugate into liposomes using a glutathione-gradient loading method, and its toxicities and in vivo antitumor efficacy were compared with free VP16 in the LLC lung cancer xenograft. It was found that the repeated injection of free VP16 induced severe splenomegaly, lymphocytosis, and extensive lymphocyte infil-tration in various tissues, indicating a sign of VP16 therapy-related leukemia. By contrast, the liposomal VP16 not only remarkably alleviated the syndrome of leukemogenesis, but also exhibited significantly enhanced antitumor activity as compared with free VP16 at the same dose. These results highlighted that the liposomal VP16 having a sustained drug release could effectively decrease the toxicity of leukemogenesis, which provided a new warranty to develop liposomal VP16 as a safe alternative to the commercial VP16 injection."

基金机构："National Natural Science Foundation of China [82204308]; Sichuan Science and Technology Program [2023NSFSC0680]; Disciplinary Construction Innovation Team Foundation of Chengdu Medical College [CMC-XK-2104]; Chengdu Medical College Graduate Innovation Fund Project [YCX2022-01-25, YCX2023-01-31, YCX2023-01-36]; Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College [YLZBZ2006]; National Undergraduate Training Program for Innovation and Entrepreneurship [S202213705074, 202213705027, 202313705007, 202313705002]"

基金资助正文："This research was supported by the National Natural Science Foundation of China (No. 82204308) , Sichuan Science and Technology Program (No.2023NSFSC0680) , Disciplinary Construction Innovation Team Foundation of Chengdu Medical College (CMC-XK-2104) , Chengdu Medical College Graduate Innovation Fund Project (YCX2022-01-25, YCX2023-01-31, and YCX2023-01-36) , Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College (YLZBZ2006) , and National Undergraduate Training Program for Innovation and Entrepreneurship (S202213705074, 202213705027, 202313705007, and 202313705002) ."