10.1021/acsnano.8b05408.s001 Christopher Weldon Christopher Weldon Tianjiao Ji Tianjiao Ji Minh-Thuy Nguyen Minh-Thuy Nguyen Alina Rwei Alina Rwei Weiping Wang Weiping Wang Yi Hao Yi Hao Chao Zhao Chao Zhao Manisha Mehta Manisha Mehta Bruce Y. Wang Bruce Y. Wang Jonathan Tsui Jonathan Tsui Robert P. Marini Robert P. Marini Daniel S. Kohane Daniel S. Kohane Nanoscale Bupivacaine Formulations To Enhance the Duration and Safety of Intravenous Regional Anesthesia American Chemical Society 2018 anesthetic dose M-Bup anesthesia safety Intravenous Regional Anesthesia Intravenous rat tail vein IVRA model postoperative pain relief L-Bup Nanoscale Bupivacaine Formulations 100 nm liposomal bupivacaine tourniquet removal 2018-10-23 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Nanoscale_Bupivacaine_Formulations_To_Enhance_the_Duration_and_Safety_of_Intravenous_Regional_Anesthesia/7358720 Intravenous 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.