@article{feac7255e59c49968d078ea581148a4e,
title = "Preclinical evaluation of a hypotonic docetaxel nanosuspension formulation for intravesical treatment of non-muscle-invasive bladder cancer",
abstract = "Abstract: Intravesical chemotherapy is a key approach for treating refractory non-muscle-invasive bladder cancer (NMIBC). However, the effectiveness of intravesical chemotherapy is limited by bladder tissue penetration and retention. Here, we describe the development of a docetaxel nanosuspension that, when paired with a low osmolality (hypotonic) vehicle, demonstrates increased uptake by the bladder urothelium with minimal systemic exposure. We compare the bladder residence time and efficacy in an immune-competent rat model of NMIBC to the clinical comparator, solubilized docetaxel (generic Taxotere) diluted for intravesical administration. We found that only the intravesical docetaxel nanosuspension significantly decreased cell proliferation compared to untreated tumor tissues. The results presented here suggest that the combination of nanoparticle-based chemotherapy and a hypotonic vehicle can provide more efficacious local drug delivery to bladder tissue for improved treatment of refractory NMIBC. Graphical abstract: [Figure not available: see fulltext.]",
keywords = "Chemotherapy, N-methyl-N-nitrosourea (MNU), Nanomilling, Pluronic, Taxotere, Urothelium",
author = "Date, {Abhijit A.} and Max Kates and Takahiro Yoshida and Taarika Babu and Umara Afzal and Pranjali Kanvinde and Alexander Baras and Nicole Anders and Ping He and Michelle Rudek and Justin Hanes and Bivalacqua, {Trinity J.} and Ensign, {Laura M.}",
note = "Funding Information: We thank the JHMI animal husbandry staff, the JHMI Reference Histology lab, and the Wilmer Microscopy and Imaging Core Facility (MICF) funded by NIH grant P30EY001765. We thank Dr. Fareeha Zulfiqar for her help with the osmolarity measurements. We would also like to thank BASF Corporation for providing free samples of stabilizers used in this study. Drug measurements were supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins [NIH grants P30CA006973 and UL1TR001079, and the Shared Instrument Grant (S10RR026824)]. The project described was also supported by grant number UL1 TR001079 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCATS or NIH. This work was supported by a grant from the Johns Hopkins Greenberg Bladder Cancer Institute. Funding Information: We thank the JHMI animal husbandry staff, the JHMI Reference Histology lab, and the Wilmer Microscopy and Imaging Core Facility (MICF) funded by NIH grant P30EY001765. We thank Dr. Fareeha Zulfiqar for her help with the osmolarity measurements. We would also like to thank BASF Corporation for providing free samples of stabilizers used in this study. Drug measurements were supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins [NIH grants P30CA006973 and UL1TR001079, and the Shared Instrument Grant (S10RR026824)]. The project described was also supported by grant number UL1 TR001079 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCATS or NIH. This work was supported by a grant from the Johns Hopkins Greenberg Bladder Cancer Institute. Publisher Copyright: {\textcopyright} 2020, Controlled Release Society.",
year = "2021",
month = oct,
doi = "10.1007/s13346-020-00870-w",
language = "English (US)",
volume = "11",
pages = "2085--2095",
journal = "Drug Delivery and Translational Research",
issn = "2190-393X",
publisher = "Springer Publishing Company",
number = "5",
}