Tumor treatment with microbubble enhanced low-intensity ultrasound and paclitaxel nanocapsules reduces drug dose required for therapeutic effect
Ultrasonics Symposium(2011)
Abstract
Applying ultrasound in conjunction with microbubbles at the tumor site can enhance vascular permeability and motivate nanoparticle extravasation. We combine low intensity ultrasound (US) and microbubbles (MB) with drug-bearing nanocapsules (NC) to improve the therapeutic index of paclitaxel. Female mice bearing 4T1 mammary carcinoma tumors received one of five treatments: paclitaxel NC only at 2.5 mg/kg; paclitaxel NC only at 5 mg/kg; paclitaxel NC (2.5 mg/kg) prior to two minutes of therapeutic US exposure; paclitaxel NC (2.5 mg/kg) co-administered with MB prior to two minutes of therapeutic US; and control. Therapeutic US was applied using a Sonicator 740 system operated at 1 MHz, 2 W/cm2, and 10% duty cycle. At 2.5 mg/kg, mice treated with NC+MB+US had slower tumor growth compared to treatment with NC or NC+US. A statistically significant difference between NC+MB+US and both NC and NC+US groups was seen on multiple days. Data suggest treating at a dose of 2.5 mg/kg with NC+MB+US is as effective as treating with NC alone at 5 mg/kg. This finding is significant because lowering a treatment dose may reduce the risk of unwanted side effects.
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Key words
biomedical ultrasonics,bubbles,cancer,drug delivery systems,drugs,nanomedicine,nanoparticles,organic compounds,tumours,4t1 mammary carcinoma tumors,sonicator 740 system,drug dose,drug-bearing nanocapsules,duty cycle,female mice,frequency 1 mhz,microbubble enhanced low-intensity ultrasound,nanoparticle extravasation,paclitaxel nanocapsules,therapeutic us exposure,therapeutic effect,therapeutic index,time 2 min,tumor growth,tumor site,tumor treatment,vascular permeability,contrast agent,drug delivery,microbubble,nanoparticle,therapeutic
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