Microbubble-mediated ultrasonic techniques for improved chemotherapeutic delivery in cancer

• Published in: Journal of drug targeting Vol. 20; no. 1; pp. 43 - 54
• Main Authors: Sorace, Anna G., Warram, Jason M., Umphrey, Heidi, Hoyt, Kenneth
• Format: Journal Article
• Language: English
• Published: London Informa Healthcare 01-01-2012; Taylor & Francis
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - metabolism; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; cancer; chemotherapy; drug delivery; Drug Delivery Systems - methods; Female; General pharmacology; Humans; Medical sciences; Mice; Mice, Nude; microbubble contrast agents; Microbubbles - therapeutic use; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Tumor Cells, Cultured; Ultrasonic Therapy - methods; Ultrasound; Xenograft Model Antitumor Assays - methods; Chemotherapy; Treatment; Pharmaceutical technology; Drug carrier; microbubble contrast agents; Malignant tumor; drug delivery; Ultrasound; Contrast media; Cancer
• ISSN: 1061-186X; 1029-2330
• DOI: 10.3109/1061186X.2011.622397

Background: Ultrasound (US) exposed microbubble (MB) contrast agents have the capability to transiently enhance cell membrane permeability. Using this technique in cancer treatment to increase the efficiency of chemotherapy through passive, localized delivery has been an emerging area of research.
Purpose: Investigation of the influence of US parameters on MB-mediated drug delivery in cancer.
Methods: The 2LMP breast cancer cells were used for in vitro experiments and 2LMP tumor-bearing mice were used during in vivo experiments. Changes in membrane permeability were investigated after the influence of MB-mediated US therapy parameters (i.e. frequency, mechanical index, pulse repetition period, US duration, and MB dosing and characteristics) on cancer cells. Calcein, a non-permeable fluorescent molecule, and Taxol, chemotherapeutic, were used to evaluate membrane permeability. Tumor response was also assessed histologically.
Results: Combination chemotherapy and MB-mediated US therapy with optimized parameters increased cancer cell death by 50% over chemotherapy alone.
Discussion: Increased cellular uptake of chemotherapeutic was dependent upon US system parameters.
Conclusion: Optimized MB-mediated US therapy has the potential to improve cancer patient response to therapy via increased localized drug uptake, which may lead to a lowering of chemotherapeutic drug dosages and systemic toxicity.