Sonopermeation Enhances Uptake and Therapeutic Effect of Free and Encapsulated Cabazitaxel

Sofie Snipstad; Ýrr Mørch; Einar Sulheim; Andreas Åslund; André Pedersen; Catharina de Lange Davies; Rune Hansen; Sigrid Berg

doi:10.1016/j.ultrasmedbio.2020.12.026

Sonopermeation Enhances Uptake and Therapeutic Effect of Free and Encapsulated Cabazitaxel

Ultrasound Med Biol. 2021 May;47(5):1319-1333. doi: 10.1016/j.ultrasmedbio.2020.12.026. Epub 2021 Feb 3.

Authors

Sofie Snipstad¹, Ýrr Mørch², Einar Sulheim³, Andreas Åslund², André Pedersen⁴, Catharina de Lange Davies⁵, Rune Hansen⁶, Sigrid Berg⁷

Affiliations

¹ Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway; Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway; Cancer Clinic, St. Olav's Hospital, Trondheim, Norway. Electronic address: sofie.snipstad@sintef.no.
² Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
³ Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway; Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway; Cancer Clinic, St. Olav's Hospital, Trondheim, Norway.
⁴ Department of Health Research, SINTEF Digital, Trondheim, Norway.
⁵ Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
⁶ Department of Health Research, SINTEF Digital, Trondheim, Norway; Department of Circulation and Medical imaging, Norwegian University of Science and Technology, Trondheim, Norway.
⁷ Cancer Clinic, St. Olav's Hospital, Trondheim, Norway; Department of Health Research, SINTEF Digital, Trondheim, Norway; Department of Circulation and Medical imaging, Norwegian University of Science and Technology, Trondheim, Norway.

PMID: 33549379
DOI: 10.1016/j.ultrasmedbio.2020.12.026

Abstract

Delivery of drugs and nanomedicines to tumors is often heterogeneous and insufficient and, thus, of limited efficacy. Microbubbles in combination with ultrasound have been found to improve delivery to tumors, enhancing accumulation and penetration. We used a subcutaneous prostate cancer xenograft model in mice to investigate the effect of free and nanoparticle-encapsulated cabazitaxel in combination with ultrasound and microbubbles with a lipid shell or a shell of nanoparticles. Sonopermeation reduced tumor growth and prolonged survival (26%-100%), whether the free drug was co-injected with lipid-shelled microbubbles or the nanoformulation was co-injected with lipid-shelled or nanoparticle-shelled microbubbles. Coherently with the improved therapeutic response, we found enhanced uptake of nanoparticles directly after ultrasound treatment that lasted several weeks (2.3 × -15.8 × increase). Neither cavitation dose nor total accumulation of nanoparticles could explain the variation within treatment groups, emphasizing the need for a better understanding of the tumor biology and mechanisms involved in ultrasound-mediated treatment.

Keywords: Cabazitaxel; Cavitation; Drug delivery; Microbubbles; Nanomedicine; Nanoparticles; Sonochemotherapy; Sonopermeation; Sonoporation; Ultrasound.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Combined Modality Therapy
Drug Delivery Systems / methods*
Heterografts
Male
Mice
Mice, Inbred BALB C
Microbubbles*
Nanoparticles*
Prostatic Neoplasms / drug therapy*
Taxoids / administration & dosage*
Taxoids / pharmacokinetics*
Treatment Outcome
Ultrasonic Therapy

Substances

Taxoids
cabazitaxel