PT  - JOURNAL ARTICLE
AU  - Peng-Fei Sun
AU  - Tian Tian
AU  - Li-Na Chen
AU  - Rong-Guo Fu
AU  - Shan-Shan Xu
AU  - Hong Ai
AU  - Bing Wang
AU  - Jian Zhang
AU  - Ruo-Yan Si
AU  - Zhonglin Chai
AU  - Mark E. Cooper
AU  - Shu-Ting Ren
TI  - Ultrasound Combined with Microbubbles Enhances the Effects of Methylprednisolone in Lipopolysaccharide-Induced Human Mesangial Cells
AID  - 10.1124/jpet.117.246223
DP  - 2018 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 476--484
VI  - 365
IP  - 3
4099  - http://jpet.aspetjournals.org/content/365/3/476.short
4100  - http://jpet.aspetjournals.org/content/365/3/476.full
SO  - J Pharmacol Exp Ther2018 Jun 01; 365
AB  - A novel drug delivery system mediated by ultrasound (US) combined with microbubbles (MBs) (US+MB) could improve local drug concentration to enhance its efficacy. To investigate the influence of US+MB on methylprednisolone (MP), the effect of US+MB combined with MP (US+MB+MP) on lipopolysaccharide (LPS)-induced human mesangial cells (HMCs) and the underlying mechanism were explored in this study. The results revealed that HMCs treated with LPS underwent significant proliferation and exhibited an increase in nuclear transcription factor-κB (NF-κB) and transforming growth factor-β1 (TGF-β1) expression and a decrease in cellular apoptosis. This effect was significantly inhibited by MP (30–100 μg/ml), US combined with MBs (3.22 × 107 and 8.05 × 107 bubbles/ml), and US combined with both MBs (1.29 × 107 bubbles/ml) and MP (12 μg/ml) (US+MB1+MP12). The effect of US+MB1+MP12 was better than the effect of 12 μg/ml of MP alone and was similar to the effect of 100 μg/ml of MP. Additionally, the intracellular free MP content was significantly higher in the US+MB1+MP12 group than in the MP12 group. US combined with MBs not only inhibited LPS-induced HMC proliferation and NF-κB and TGF-β1 expression and increased cellular apoptosis but also synergized with the pharmacologic effect of MP. The mechanism is partially due to the US-assisted MB local drug delivery and the anti-inflammatory effect induced by US combined with MBs.