@article{fbb6807a1d394eb6b67c93f20090f816,
title = "Head-to-head comparative pharmacokinetic and biodistribution (PK/BD) study of two dexamethasone prodrug nanomedicines on lupus-prone NZB/WF1 mice",
abstract = "HPMA copolymer-based dexamethasone prodrug (P-Dex) and PEG-based dexamethasone prodrug (PEG-Dex, ZSJ-0228) were previously found to passively target the inflamed kidney and provide potent and sustained resolution of nephritis in NZB/WF1 lupus-prone mice. While both prodrug nanomedicines effectively ameliorate lupus nephritis, they have demonstrated distinctively different safety profiles. To explore the underlining mechanisms of these differences, we conducted a head-to-head comparative PK/BD study of P-Dex and PEG-Dex on NZB/WF1 mice. Overall, the systemic organ/tissue exposures to P-Dex and Dex released from P-Dex were found to be significantly higher than those of PEG-Dex. The high prodrug concentrations were sustained in kidney for only 24 h, which cannot explain their lasting therapeutic efficacy (>1 month). P-Dex showed sustained presence in liver, spleen and adrenal gland, while the presence of PEG-Dex in these organs was transient. This difference in PK/BD profiles may explain PEG-Dex{\textquoteright} superior safety than P-Dex.",
keywords = "Dexamethasone, Lupus nephritis, P-Dex, Pharmacokinetics and biodistribution, Prodrug nanomedicine, ZSJ-0228",
author = "Xin Wei and Gang Zhao and Xiaobei Wang and Nagsen Gautam and Zhenshan Jia and Zhifeng Zhao and Dexuan Kong and Fan Zhang and Sushil Kumar and Yuanyuan Sun and Ningrong Chen and Xiaoyan Wang and Libin Yang and Rongguo Ren and Thiele, {Geoffrey M.} and Bronich, {Tatiana K.} and O'Dell, {James R.} and Yazen Alnouti and Dong Wang",
note = "Funding Information: Funding: This study was supported in part by the National Institute of Allergy and Infectious Diseases of the United States National Institute of Health ( R01 AI119090 ), China Scholarship Council (XW, GZ, DK, FZ., NC., LY), and UNMC College of Pharmacy . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: Funding: This study was supported in part by the National Institute of Allergy and Infectious Diseases of the United States National Institute of Health (R01 AI119090), China Scholarship Council (XW, GZ, DK, FZ., NC., LY), and UNMC College of Pharmacy. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflicts of Interests: DW, ZSJ and XBW are co-inventors of the patent (PCT/US16/61728), which covers ZSJ-0228 prodrug technology. DW is a co-founder of Shannon Pharmaceuticals, which has licensed the technology for preclinical and clinical development. Shannon provides DW's laboratory with funding for Chemistry Manufacturing and Controls (CMC) development. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = oct,
doi = "10.1016/j.nano.2020.102266",
language = "English (US)",
volume = "29",
journal = "Nanomedicine: Nanotechnology, Biology, and Medicine",
issn = "1549-9634",
publisher = "Elsevier Inc.",
}