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Nanoanesthesia: A Novel, Intravenous Approach to Ankle Block in the Rat by Magnet-Directed Concentration of Ropivacaine-Associated Nanoparticles

Mantha, Venkat R. R. FFARCSI*; Nair, Harsha K.*; Venkataramanan, Raman PhD; Gao, Yuan Yue MS; Matyjaszewski, Krzysztof PhD; Dong, Hongchen PhD; Li, Wenwen PhD; Landsittel, Doug PhD§‖; Cohen, Elan MS§; Lariviere, William R. PhD*

doi: 10.1213/ANE.0000000000000175
Regional Anesthesia: Research Report

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 (Fe3O4). 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.

Supplemental Digital Content is available in the text.Published ahead of print April 10, 2014

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.

Harsha K. Nair is a Medical Student, SUNY, Buffalo, New York.

Hongchen Dong, PhD, is currently affiliated with GE Global Research Center, Niskayuna, New York.

Wenwen Li, PhD, is currently affiliated with Dow Chemicals, Freeport, Texas.

Accepted for publication December 19, 2013.

Published ahead of print April 10, 2014

Funding: Supported by a grant from: The Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA.

The authors declare no conflicts of interest.

This work has been presented in part at the “Science 2010” symposium, University of Pittsburgh, October 2010, and the International Anesthesia Research Society, 85th Annual Meeting, May 2011.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site.

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Address correspondence to Venkat R. R. Mantha, FFARCSI, Department of Anesthesiology, University of Pittsburgh School of Medicine, Magee-Womens Hospital, 300 Halket St., Pittsburgh, PA 15213. Address e-mail;

© 2014 International Anesthesia Research Society