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通过兆赫兹高强度超声将药物局部递送至关节软骨

Delivering Agents Locally into Articular Cartilage by Intense MHz Ultrasound.

作者信息

Nieminen Heikki J, Ylitalo Tuomo, Suuronen Jussi-Petteri, Rahunen Krista, Salmi Ari, Saarakkala Simo, Serimaa Ritva, Hæggström Edward

机构信息

Department of Physics, University of Helsinki, Helsinki, Finland.

Department of Physics, University of Helsinki, Helsinki, Finland; Research Center for Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.

出版信息

Ultrasound Med Biol. 2015 Aug;41(8):2259-65. doi: 10.1016/j.ultrasmedbio.2015.03.025. Epub 2015 Apr 25.

DOI:10.1016/j.ultrasmedbio.2015.03.025
PMID:25922135
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4587538/
Abstract

There is no cure for osteoarthritis. Current drug delivery relies on systemic delivery or injections into the joint. Because articular cartilage (AC) degeneration can be local and drug exposure outside the lesion can cause adverse effects, localized drug delivery could permit new drug treatment strategies. We investigated whether intense megahertz ultrasound (frequency: 1.138 MHz, peak positive pressure: 2.7 MPa, Ispta: 5 W/cm(2), beam width: 5.7 mm at -6 dB, duty cycle: 5%, pulse repetition frequency: 285 Hz, mechanical index: 1.1) can deliver agents into AC without damaging it. Using ultrasound, we delivered a drug surrogate down to a depth corresponding to 53% depth of the AC thickness without causing histologically detectable damage to the AC. This may be important because early osteoarthritis typically exhibits histopathologic changes in the superficial AC. In conclusion, we identify intense megahertz ultrasound as a technique that potentially enables localized non-destructive delivery of osteoarthritis drugs or drug carriers into articular cartilage.

摘要

骨关节炎无法治愈。目前的药物递送依赖于全身给药或关节内注射。由于关节软骨(AC)退变可能是局部性的,且病变外的药物暴露会引起不良反应,局部药物递送可能会带来新的药物治疗策略。我们研究了高强度兆赫超声(频率:1.138兆赫,正峰值压力:2.7兆帕,空间平均时间平均声强:5瓦/平方厘米,-6分贝时波束宽度:5.7毫米,占空比:5%,脉冲重复频率:285赫兹,机械指数:1.1)能否在不损伤AC的情况下将药物递送至其中。通过超声,我们将一种药物替代物递送至相当于AC厚度53%深度的位置,且未对AC造成组织学上可检测到的损伤。这可能很重要,因为早期骨关节炎通常在AC表层表现出组织病理学变化。总之,我们确定高强度兆赫超声是一种有可能实现将骨关节炎药物或药物载体局部无损递送至关节软骨的技术。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/29807a84e007/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/5ff314c2b85d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/6d52b0b547b7/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/202d1f3b6433/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/942d8e53f442/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/0bf27f15db71/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/29807a84e007/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/5ff314c2b85d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/6d52b0b547b7/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/202d1f3b6433/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/942d8e53f442/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/0bf27f15db71/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fa/4617473/29807a84e007/gr6.jpg

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