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

Authors
  • Date, Abhijit A1, 2, 3
  • Kates, Max4, 5
  • Yoshida, Takahiro4
  • Babu, Taarika6
  • Afzal, Umara1, 7
  • Kanvinde, Pranjali1
  • Baras, Alexander4, 5, 8
  • Anders, Nicole9
  • He, Ping9
  • Rudek, Michelle9
  • Hanes, Justin1, 2, 6, 9, 8
  • Bivalacqua, Trinity J10, 11
  • Ensign, Laura M12, 13, 14, 15, 16
  • 1 The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, USA.
  • 2 Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, USA.
  • 3 Present address: The Daniel K. Inouye College of Pharmacy, University of Hawaii Hilo, 200 W. Kawili Street, Hilo, HI, USA.
  • 4 Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, USA.
  • 5 Greenberg Bladder Cancer Institute, Johns Hopkins Medical Institutions, Baltimore, USA.
  • 6 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, USA.
  • 7 Department of Biochemistry, PMAS-Arid Agriculture University, Muree Road, Shamsabad Rawalpindi, Pakistan. , (Pakistan)
  • 8 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, USA.
  • 9 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, USA.
  • 10 Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, USA. [email protected]
  • 11 Greenberg Bladder Cancer Institute, Johns Hopkins Medical Institutions, Baltimore, USA. [email protected]
  • 12 The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, USA. [email protected]
  • 13 Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, USA. [email protected]
  • 14 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, USA. [email protected]
  • 15 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, USA. [email protected]
  • 16 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, USA. [email protected]
Type
Published Article
Journal
Drug delivery and translational research
Publication Date
Oct 01, 2021
Volume
11
Issue
5
Pages
2085–2095
Identifiers
DOI: 10.1007/s13346-020-00870-w
PMID: 33164163
Source
Medline
Keywords
Language
English
License
Unknown

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. © 2020. Controlled Release Society.

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