Abstract
Localized delivery of drugs into an osteoarthritic cartilaginous lesion does not yet exist, which limits pharmaceutical management of osteoarthritis (OA). High-intensity focused ultrasound (HIFU) provides a means to actuate matter from a distance in a non-destructive way. In this study, we aimed to deliver methylene blue locally into bovine articular cartilage in vitro. HIFU-treated samples (n = 10) were immersed in a methylene blue (MB) solution during sonication (f = 2.16 MHz, peak-positive-pressure = 3.5 MPa, mechanical index = 1.8, pulse repetition frequency = 3.0 kHz, cycles per burst: 50, duty cycle: 7%). Adjacent control 1 tissue (n = 10) was first pre-treated with HIFU followed by immersion into MB; adjacent control 2 tissue (n = 10) was immersed in MB without ultrasound exposure. The MB content was higher (p < 0.05) in HIFU-treated samples all the way to a depth of 600 µm from AC surface when compared to controls. Chondrocyte viability and RNA expression levels associated with cartilage degeneration were not different in HIFU-treated samples when compared to controls (p > 0.05). To conclude, HIFU delivers molecules into articular cartilage without major short-term concerns about safety. The method is a candidate for a future approach for managing OA.
Highlights
Localized delivery of drugs into an osteoarthritic cartilaginous lesion does not yet exist, which limits pharmaceutical management of osteoarthritis (OA)
We investigate if High-intensity focused ultrasound (HIFU) can deliver a 320 Da sized molecule into articular cartilage (AC) without affecting the short-term viability or RNA expression of chondrocytes
Bovine osteochondral samples that were immersed in a contrast agent while being sonicated (T1 and femoral condyle) (Fig. 1, Table 1) were colored with pronounced blue intensity compared to adjacent tissue
Summary
Localized delivery of drugs into an osteoarthritic cartilaginous lesion does not yet exist, which limits pharmaceutical management of osteoarthritis (OA). We demonstrated that laser ultrasound -induced shock waves (center frequency 3 MHz) were capable of delivering 320 Da molecules to a depth of 600 μm in a clinically relevant timeframe of 11 minutes[21] This induced no structural damage to the AC and neither affected AC cell (chondrocyte) viability nor their RNA expression[21]. It seems that HIU provides a means to deliver molecules whose size is equivalent to that of drugs into AC without significant short-term adverse effects to AC. We investigate if HIFU can deliver a 320 Da sized molecule into AC without affecting the short-term viability or RNA expression of chondrocytes
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