Preclinical evaluation of a hypotonic docetaxel nanosuspension formulation for intravesical treatment of non-muscle-invasive bladder cancer

Abhijit A. Date, Max Kates, Takahiro Yoshida, Taarika Babu, Umara Afzal, Pranjali Kanvinde, Alexander Baras, Nicole Anders, Ping He, Michelle Rudek, Justin Hanes, Trinity J. Bivalacqua, Laura Ensign-Hodges

Research output: Contribution to journalArticlepeer-review

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.]

Original languageEnglish (US)
JournalDrug Delivery and Translational Research
DOIs
StateAccepted/In press - 2020

Keywords

  • Chemotherapy
  • N-methyl-N-nitrosourea (MNU)
  • Nanomilling
  • Pluronic
  • Taxotere
  • Urothelium

ASJC Scopus subject areas

  • Pharmaceutical Science

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