Tumor treatment with microbubble enhanced low-intensity ultrasound and paclitaxel nanocapsules reduces drug dose required for therapeutic effect

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.