TY - JOUR
T1 - Delivering Agents Locally into Articular Cartilage by Intense MHz Ultrasound
AU - Nieminen, Heikki J.
AU - Ylitalo, Tuomo
AU - Suuronen, Jussi Petteri
AU - Rahunen, Krista
AU - Salmi, Ari
AU - Saarakkala, Simo
AU - Serimaa, Ritva
AU - Hæggström, Edward
N1 - Funding Information:
We thank the Academy of Finland (Projects 253579 , 268378 and 273571 ) and the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013, ERC Grant Agreement 336267) for financial support. We are grateful to Lihakonttori Oy (Helsinki, Finland) for providing bovine knees. We warmly thank Dr. S. Adam Hacking, Ph.D. and Prof. Kenneth P. H. Pritzker, M.D., FRCPC for their constructive criticism. We are grateful to Mr. Alexander Meaney for assistance with the XMT imaging of sample 1. We thank Mr. Eetu Lampsijärvi, Mr. Jari Rinta-aho and Mr. Nestori Westerlund for assistance with experiments and Mr. Christoffer Fridlund for assistance in sample preparation. We are grateful to Ms. Ida Holopainen and Mr. Anton Nolvi, B.Sc. for their help in technical drawing.
Publisher Copyright:
© 2015 World Federation for Ultrasound in Medicine & Biology.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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/cm2, 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 beimportant 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.
AB - 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/cm2, 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 beimportant 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.
KW - Cartilage repair
KW - Drug delivery
KW - Osteoarthritis
KW - Ultrasound
UR - http://www.scopus.com/inward/record.url?scp=84930537603&partnerID=8YFLogxK
U2 - 10.1016/j.ultrasmedbio.2015.03.025
DO - 10.1016/j.ultrasmedbio.2015.03.025
M3 - Article
C2 - 25922135
AN - SCOPUS:84930537603
SN - 0301-5629
VL - 41
SP - 2259
EP - 2265
JO - ULTRASOUND IN MEDICINE AND BIOLOGY
JF - ULTRASOUND IN MEDICINE AND BIOLOGY
IS - 8
ER -