Abstract
Localized delivery of drugs into articular cartilage (AC) may facilitate the development of novel therapies to treat osteoarthritis (OA). We investigated the potential of spark-gap-generated sound to deliver a drug surrogate, i.e. methylene blue (MB), into AC. In-vitro experiments exposed bovine AC samples to either simultaneous sonication and immersion in MB (Treatment 1; n = 10), immersion in MB after sonication (Control 1; n = 10), solely immersion in MB (Control 2; n = 10), or neither sonication nor immersion in MB (Control 3; n = 10). The sonication protocol consisted of 1000 spark-gap -generated pulses. Delivery of MB into AC was estimated from optical absorbance in transmission light microscopy. Optical absorbance was significantly greater in the treatment group up to 900 µm depth from AC surface as compared to all controls. Field emission scanning electron microscopy (FESEM), histological analysis, and digital densitometry (DD) of sonicated (n = 6) and non-sonicated (n = 6) samples showed no evidence of sonication-induced changes in AC. Consequently, spark-gap -generated sound may offer a solution for localized drug delivery into AC in a non-destructive fashion. Further research on this method may contribute to OA drug therapies.
Highlights
The socioeconomic burden that Osteoarthritis (OA) represents to individuals and society is rising rapidly
We found a significantly different (p < 0.01) optical absorbance (assumed to linearly depend on methylene blue (MB) concentration in articular cartilage (AC)) in the treated group (T1) as compared to controls Control 1 (C1) and Control 2 (C2) from 0 to 900 μm depth (Figure 3)
Based on field emission scanning electron microscopy (FESEM) imaging, we found no distinguishable difference in the superficial AC structure between DTa and DCa (Figure 4B)
Summary
The socioeconomic burden that Osteoarthritis (OA) represents to individuals and society is rising rapidly. In the USA alone, the number of patients diagnosed with OA increased from 21 million to 27 million between 1995 and 2007 [1]. The Global Burden of Disease Study 2010 estimated that knee OA affects nearly 250 million persons [2]. OA, a condition strongly associated with pain and reduced mobility, was responsible for more than 17 million years lived with disability (YLDs) [2, 3]. While no effective therapy to treat OA is yet available, recent research shows promising disease-modifying properties of several drug candidates [4,5,6].
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