Enhancing Nab-Paclitaxel Delivery Using Microbubble-Assisted Ultrasound in a Pancreatic Cancer Model

Mol Pharm. 2019 Sep 3;16(9):3814-3822. doi: 10.1021/acs.molpharmaceut.9b00416. Epub 2019 Aug 6.

Abstract

A combination of microbubbles (MBs) and ultrasound (US) is an emerging method for noninvasive and targeted enhancement of anti-cancer drug uptake. This method showed an increase local drug extravasation in tumor tissue while reducing the systemic adverse effects in various tumor models. The present study aims to evaluate the effectiveness of this approach for Nab-paclitaxel delivery in a pancreatic tumor model. US and MBs of different types in combination with Nab-paclitaxel showed a loss in cell viability of pancreatic cancer cells in comparison with Nab-paclitaxel treatment alone in in vitro scenario. The in vivo data revealed that US and MBs in combination with Nab-paclitaxel induced a significant decrease in the tumor volume in a subcutaneous pancreatic adenocarcinoma mouse model in comparison to tumors treated with Nab-paclitaxel alone. The postmortem anatomopathological analyses of tumor tissues partially confirmed these results. In conclusion, this study demonstrates that MB-assisted US is a relevant technology to increase the therapeutic effectiveness of Nab-paclitaxel in a pancreatic cancer model.

Keywords: Nab-paclitaxel; microbubble; pancreatic cancer; sonoporation; ultrasound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / therapeutic use*
  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Cell Line, Tumor
  • Cell Membrane Permeability / drug effects
  • Cell Survival / drug effects
  • Contrast Media / therapeutic use*
  • Drug Delivery Systems / methods*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microbubbles / therapeutic use*
  • Nanoparticles / chemistry*
  • Paclitaxel / therapeutic use*
  • Pancreatic Neoplasms / drug therapy
  • Tumor Burden / drug effects
  • Ultrasonography / methods*
  • Xenograft Model Antitumor Assays

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antineoplastic Agents, Phytogenic
  • Contrast Media
  • Paclitaxel