nn8b05408_si_001.pdf (1013.33 kB)
Nanoscale Bupivacaine Formulations To Enhance the Duration and Safety of Intravenous Regional Anesthesia
journal contribution
posted on 2018-10-23, 00:00 authored by Christopher Weldon, Tianjiao Ji, Minh-Thuy Nguyen, Alina Rwei, Weiping Wang, Yi Hao, Chao Zhao, Manisha Mehta, Bruce Y. Wang, Jonathan Tsui, Robert
P. Marini, Daniel S. KohaneIntravenous
regional anesthesia (IVRA; Bier block) is commonly
used to anesthetize an extremity for surgery. Limitations of the procedure
include pain from the required tourniquet, the toxicity that can occur
from systemic release of local anesthetics, and the lack of postoperative
pain relief. We hypothesized that the nanoencapsulation of the local
anesthetic would prolong local anesthesia and enhance safety. Here,
we developed an ∼15 nm micellar bupivacaine formulation (M-Bup)
and tested it in a rat tail vein IVRA model, in which active agents
were restricted in the tail by a tourniquet for 15 min. After tourniquet
removal, M-Bup provided local anesthesia for 4.5 h, which was two
times longer than that from a larger dose of free bupivacaine. Approximately
100 nm liposomal bupivacaine (L-Bup) with the same drug dose as M-Bup
did not cause anesthesia. Blood levels of bupivacaine after tourniquet
removal were lower in animals receiving M-Bup than L-Bup or free bupivacaine,
demonstrating enhanced safety. Tissue reaction to M-Bup was benign.