School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, People's Republic of China.
Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control, School of Mechanical Engineering, Tianjin University of Technology, Tianjin, 300382, China.
Drug Deliv Transl Res. 2024 Dec;14(12):3621-3639. doi: 10.1007/s13346-024-01695-7. Epub 2024 Aug 15.
Local intra-articular administration with minimal side effects and rapid efficacy is a promising strategy for treating osteoarthritis(OA). Most drugs are rapidly cleared from the joint space by capillaries and lymphatic vessels before free diffusion into cartilage. Ultrasound, as a non-invasive therapy, enhances molecular transport within cartilage through the mechanisms of microbubble cavitation and thermal effects. This study investigated the mass transfer behavior of solute molecules with different molecular weights (479 Da, 40 kDa, 150 kDa) within porcine articular cartilage under low-frequency ultrasound conditions of 40 kHz and ultrasound intensities of 0.189 W/cm and 0.359 W/cm. The results revealed that under the conditions of 0.189 W/cm ultrasound intensity, the mass transfer concentration of solute molecules were higher compared to passive diffusion, and with an increase in ultrasound intensity to 0.359 W/cm, the mass transfer effect within the cartilage was further enhanced. Ultrasound promotes molecular transport in different layers of cartilage. Under static conditions, after 2 h of mass transfer, the concentration of small molecules in the superficial layer is lower than that in the middle layer. After applying ultrasound at 0.189 W/cm, the molecular concentration in the superficial layer significantly increases. Under conditions of 0.359 W/cm, after 12 h of mass transfer, the concentration of medium and large molecules in the deep layer region increased by more than two times. In addition, this study conducted an assessment of damage to porcine articular cartilage under ultrasound exposure, revealing the significant potential of low-frequency, low-intensity ultrasound in drug delivery and treatment of OA.
局部关节内给药具有副作用小、疗效快的特点，是治疗骨关节炎（OA）的有前途的策略。大多数药物在自由扩散到软骨之前，会被毛细血管和淋巴管迅速清除出关节间隙。超声作为一种非侵入性治疗方法，通过微泡空化和热效应等机制增强了软骨内分子的传输。本研究在 40 kHz 的低频超声条件和 0.189 W/cm 和 0.359 W/cm 的超声强度下，研究了不同分子量（479 Da、40 kDa、150 kDa）的溶质分子在猪关节软骨内的传质行为。结果表明，在 0.189 W/cm 超声强度下，溶质分子的传质浓度高于被动扩散，随着超声强度增加到 0.359 W/cm，软骨内的传质效果进一步增强。超声促进了软骨不同层之间的分子传输。在静态条件下，经过 2 小时的传质后，浅层中小分子的浓度低于中层。在施加 0.189 W/cm 的超声后，浅层的分子浓度显著增加。在 0.359 W/cm 的条件下，经过 12 小时的传质后，深层区域中、大分子的浓度增加了两倍多。此外，本研究还评估了超声暴露对猪关节软骨的损伤，揭示了低频、低强度超声在药物输送和治疗 OA 方面的巨大潜力。
