Delivering Agents Locally into Articular Cartilage by Intense MHz Ultrasound.
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.
Department of Physics, University of Helsinki, Helsinki, Finland. Electronic address: heikki.nieminen@helsinki.fi.
Heikki J
HJ
Nieminen
Department of Physics, University of Helsinki, Helsinki, Finland; Research Center for Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
Tuomo
T
Ylitalo
Department of Physics, University of Helsinki, Helsinki, Finland.
Jussi-Petteri
JP
Suuronen
Research Center for Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
Krista
K
Rahunen
Department of Physics, University of Helsinki, Helsinki, Finland.
Ari
A
Salmi
Research Center for Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
Simo
S
Saarakkala
Department of Physics, University of Helsinki, Helsinki, Finland.
Ritva
R
Serimaa
Department of Physics, University of Helsinki, Helsinki, Finland.
Edward
E
Hæggström
D000818:Animals; D002358:Cartilage, Articular / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000528:radiation effects*; D002417:Cattle; D003287:Contrast Media; D018274:Electroporation / Q000379:methods*; D019220:High-Energy Shock Waves; D010772:Phosphotungstic Acid / Q000737:chemistry*; D013010:Sonication / Q000379:methods*; D014463:Ultrasonography
D003287:Contrast Media; D010772:Phosphotungstic Acid
Cartilage repair; Drug delivery; Osteoarthritis; Ultrasound