@article{Wang2022, 
author = {Helin Wang and Qi Lu and Yifan Miao and Jiaxuan Song and Mingyang Zhang and Zixuan Wang and Haotian Zhang and Zhonggui He and Chutong Tian and Jin Sun},
title = {Boosting SN38-based oral chemotherapy to combine reduction-bioactivated structured lipid-mimetic prodrug with ascorbic acid},
year = {2022},
journal = {Nano Research},
volume = {15},
number = {10},
pages = {9092-9104},
keywords = {oral chemotherapy, structured lipid-mimetic prodrug, 7-ethyl-10-hydroxycamptothecin (SN38), ascorbic acid},
url = {https://www.sciopen.com/article/10.1007/s12274-022-4544-7},
doi = {10.1007/s12274-022-4544-7},
abstract = {The reduction-responsive disulfide bonds have been widely used as bioactive linkages to facilitate a rapid release of anticancer drugs into tumor cells. However, the activation can be hindered by the kinetics of the thiol-disulfide exchange reactions. Supplementing with an additional reductant is a promising strategy to further boost drug release. Herein, inspired by the specific absorption mechanism of triglyceride fat, structured lipid-mimetic oral prodrugs of 7-ethyl-10-hydroxycamptothecin (SN38) were designed to improve intestinal permeability and bypass the first-pass effect. SN38 prodrugs were prepared into lipid formulations that could self-emulsify into nano-sized particles after entering the gastrointestinal tract. Surprisingly, we found that the oral bioavailability of the prodrug lipid formulation could be up to 2.69-fold higher than that of the parent SN38, indicating an effective oral delivery. In addition, the reduction-responsive disulfide bond was used as a linker, and ascorbic acid (ASC) was coadministrated to further promote the efficient release of SN38 from the prodrug. ASC enhanced the oral antitumor effect of the reduction-responsive oral prodrug and exhibited good safety. In summary, the combination of a structured lipid-mimetic prodrug and ASC was firstly demonstrated to boost the oral chemotherapy effect of the difficult-for-oral chemotherapeutics.}
}