Nanoanesthesia: a novel, intravenous approach to ankle block in the rat by magnet-directed concentration of ropivacaine-associated nanoparticles.
BACKGROUND
As an alternative to current methods of local nerve block, we studied the feasibility of producing ankle block in the rat with IV injection of magnetic nanoparticles (MNPs) associated with ropivacaine and application of a magnet at the ankle.


METHODS
The anesthetic effect of magnet-directed ropivacaine-associated MNPs (MNP/Ropiv) was tested in the rat using paw withdrawal latencies from thermal stimuli applied to the hindpaw. The MNP/Ropiv complexes consisted of 0.7% w/v ropivacaine and 0.8% w/v MNPs containing 12% w/w magnetite (F₃O₄). The effect of IV injection of MNP/Ropiv with 15, 30, and 60-minute magnet application to the right ankle was compared with the effect without magnet application on the left hindpaw, to conventional ankle block with 0.1% or 0.2% ropivacaine, and to IV injection of MNPs alone with 30-minute magnet application to the right ankle. In addition, the pharmacokinetics of the MNP/Ropiv complexes were determined.


RESULTS
IV injection of MNP/Ropiv with magnet application at the ankle significantly increased paw withdrawal latencies from thermal stimuli compared with pretreatment baselines in the same paw (P < 0.0001) and compared with the contralateral paw without magnet application (P < 0.0001). IV injection of MNPs alone had no significant effect on paw withdrawal latency. Absolute ropivacaine concentrations in ankle tissue, and ankle tissue-to-plasma concentration ratios were higher in the MNP/Ropiv group with 30-minute magnet application compared with MNP/Ropiv group without magnet application (mean ± SEM, 150 ± 10 ng/g vs 105 ± 15 ng/g, respectively, and 6.1 ± 0.8 vs 4.2 ± 0.7, respectively).


CONCLUSIONS
The current study establishes proof of principle that it is possible to produce ankle block in the rat by IV injection of MNP/Ropiv complexes and magnet application at the ankle. The results indicate that further study of this approach is warranted.
From the *Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; †Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania; ‡Center for Macromolecular Engineering, Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania; §Data Center, Center for Research on Health Care, and ‖Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Venkat R R
VR
Mantha
Harsha K
HK
Nair
Raman
R
Venkataramanan
Yuan Yue
YY
Gao
Krzysztof
K
Matyjaszewski
Hongchen
H
Dong
Wenwen
W
Li
Doug
D
Landsittel
Elan
E
Cohen
William R
WR
Lariviere
D000577:Amides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000758:Anesthesia / Q000379:methods*; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D004339:Drug Compounding; D006207:Half-Life; D006614:Hindlimb; D008280:Magnetics; D008297:Male; D053758:Nanoparticles; D009407:Nerve Block / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine