Hyperthermia Improves Solubility of Intravesical Chemotherapeutic Agents
Abstract
<jats:p>BACKGROUND: Nearly 70% of all new cases of bladder cancer are non-muscle invasive
disease, the treatment for which includes transurethral resection followed by intravesical
therapy. Unfortunately, recurrence rates approach 50% in part due to poor intravesical
drug delivery. Hyperthermia is frequently used as an adjunct to intravesical chemotherapy
to improve drug delivery and response to treatment. OBJECTIVE: To assess the solubility
profile of intravesical chemotherapies under varying conditions of pH and temperature.
METHODS: Using microplate laser nephelometry we measured the solubility of three intravesical
chemotherapy agents (mitomycin C, gemcitabine, and cisplatin) at varying physical
conditions. Drugs were assessed at room temperature (23°C), body temperature (37°C),
and 43°C, the temperature used for hyperthermic intravesical treatments. To account
for variations in urine pH, solubility was also investigated at pH 4.00, 6.00, and
8.00. RESULTS: Heat incrementally increased the solubility of all three drugs studied.
Conversely, pH largely did not impact solubility aside for gemcitabine which showed
slightly reduced solubility at pH 8.00 versus 6.00 or 4.00. Mitomycin C at the commonly
used 2.0 mg/mL was insoluble at room temperature, but soluble at both 37 and 43°C.
CONCLUSIONS: Hyperthermia as an adjunct to intravesical treatment would improve drug
solubility, and likely drug delivery as some current regimens are insoluble without
heat. Improvements in solubility also allow for testing of alternative administration
regimens to improve drug delivery or tolerability. Further studies are needed to confirm
that improvements in solubility result in increased drug delivery.</jats:p>
Type
Journal articlePermalink
https://hdl.handle.net/10161/21959Published Version (Please cite this version)
10.3233/blc-200350Publication Info
Grimberg, Dominic; Shah, Ankeet; Tan, Wei Phin; Etienne, Wiguins; Spasojevic, Ivan;
& Inman, Brant (2020). Hyperthermia Improves Solubility of Intravesical Chemotherapeutic Agents. Bladder Cancer, 6(4). pp. 461-470. 10.3233/blc-200350. Retrieved from https://hdl.handle.net/10161/21959.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Dominic Grimberg
House Staff
Brant Allen Inman
Professor of Surgery
Clinical research interests: Clinical trials of novel diagnostic tests and therapies
for genitourinary malignancies, with a strong focus on bladder cancer. Basic science
research interests: Immune therapies for cancer, hyperthermia and heat-based treatment
of cancer, molecular biology of genitourinary cancers, novel diagnostics and therapies
for genitourinary cancers
Ankeet Shah
Assistant Professor of Urology
Ivan Spasojevic
Associate Professor in Medicine
Alphabetical list of authors with Scholars@Duke profiles.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info