RESUMEN
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-ß1 (TGF-ß1) 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-ß1 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.