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Safety Assessment of Ultrasound-Assisted Intravesical Chemotherapy in Normal Dogs : A Pilot Study

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Title: Safety Assessment of Ultrasound-Assisted Intravesical Chemotherapy in Normal Dogs : A Pilot Study
Authors: Sasaki, Noboru Browse this author →KAKEN DB
Ikenaka, Yoshinori Browse this author
Aoshima, Keisuke Browse this author
Aoyagi, Teiichiro Browse this author
Kudo, Nobuki Browse this author
Nakamura, Kensuke Browse this author →KAKEN DB
Takiguchi, Mitsuyoshi Browse this author →KAKEN DB
Keywords: drug delivery
intravesical chemotherapy
non-muscle invasive bladder cancer
Issue Date: 18-Mar-2022
Publisher: Frontiers Media
Journal Title: Frontiers in pharmacology
Volume: 13
Start Page: 837754
Publisher DOI: 10.3389/fphar.2022.837754
Abstract: Intravesical chemotherapy after transurethral resection is a treatment option in patients with non-muscle invasive bladder cancer. The efficacy of intravesical chemotherapy is determined by the cellular uptake of intravesical drugs. Therefore, drug delivery technologies in the urinary bladder are promising tools for enhancing the efficacy of intravesical chemotherapy. Ultrasound-triggered microbubble cavitation may enhance the permeability of the urothelium, and thus may have potential as a drug delivery technology in the urinary bladder. Meanwhile, the enhanced permeability may increase systemic absorption of intravesical drugs, which may increase the adverse effects of the drug. The aim of this preliminary safety study was to assess the systemic absorption of an intravesical drug that was delivered by ultrasound-triggered microbubble cavitation in the urinary bladder of normal dogs. Pirarubicin, a derivative of doxorubicin, and an ultrasound contrast agent (Sonazoid) microbubbles were administered in the urinary bladder. Ultrasound (transmitting frequency 5 MHz; pulse duration 0.44 mu sec; pulse repetition frequency 7.7 kHz; peak negative pressure -1.2 MPa) was exposed to the bladder using a diagnostic ultrasound probe (PLT-704SBT). The combination of ultrasound and microbubbles did not increase the plasma concentration of intravesical pirarubicin. In addition, hematoxylin and eosin staining showed that the combination of ultrasound and microbubble did not cause observable damages to the urothelium. Tissue pirarubicin concentration in the sonicated region was higher than that of the non-sonicated region in two of three dogs. The results of this pilot study demonstrate the safety of the combination of intravesical pirarubicin and ultrasound-triggered microbubble cavitation, that is, ultrasound-assisted intravesical chemotherapy.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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