455670 Repeatable and Adjustable on-Demand Local Anesthesia By Phototriggerable Liposomes

Thursday, November 17, 2016: 8:48 AM
Golden Gate 4 (Hilton San Francisco Union Square)
Alina Rwei, Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, Robert Langer, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA and Daniel S. Kohane, Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA

Current treatment of pain relies heavily on opioids and conventional local anesthetics. The former is associated with systemic side effects and addiction (1, 2), while the latter provides short durations of anesthesia (normally 6 – 12 h when typical post-operative pain lasts for a timescale of days) (3). Although sustained release systems can provide longer nerve block durations in animal models (up to days) (4), they have a major limitation: once administered, their drug release profile cannot be changed, regardless of the patient’s changing needs. This is particularly troublesome when physical therapy or movement are desired, as motor block often accompanies the desired sensory block (4). An on-demand local anesthesia system where patients and physicians could noninvasively control the timing, intensity and duration of local anesthesia therefore highly desirable.

Here we demonstrate a phototriggerable local anesthesia system that can realize this goal. A near infrared (NIR) light-absorbing photosensitizer was encapsulated within liposomes composed of lipids labile to reactive oxygen species (ROS) (6). Upon irradiation with NIR light, the photosensitizer released singlet oxygen, inducing lipid peroxidation and enhancing the permeability of liposomal lipid bilayers, resulting in the release of encapsulated drug. A potent local anesthetic, tetrodotoxin (TTX), was loaded into these phototriggerable liposomes (Lipo-PS-TTX). In vitro experiments showed repeatable phototriggered TTX release with 730-nm laser irradiation (7). In vivo injections of Lipo-PS-TTX percutaneously onto the rat sciatic nerve induced an initial sciatic nerve block, and subsequent irradiations at 730 nm induced repeated sciatic nerve block. The timing, intensity and duration of nerve block were adjustable by the parameters of irradiation. Nerve block duration showed a clear relationship with irradiation energy density, demonstrating the controllability of the system. On-demand phototriggerable nerve block systems may allow pain treatment to be personalized and substantially improve pain management.

1. J. L. Apfelbaum, C. Chen, S. S. Mehta, T. J. Gan, Anesth Analg 97, 534 (2003).

2. M. E. Lynch, C. P. N. Watson, Pain Res Manag 11, 11 (Spring, 2006).

3. M. J. M. D. F. Fredrickson, A. F. Abeysekera, R. M. A. White, Regional Anesthesia & Pain Medicine September/October 37, 495 (2012).

4. H. Epstein-Barash et al., Proc Natl Acad Sci USA 106, 7125 (2009).

5. A. V. Soldatova et al., Inorg Chem 50, 1135 (2011/02/07, 2010).

6. Y. Yorihiro, N. Etsuo, K. Yoshio, S. Hiroyuki, Biochim Biophys Acta 795, 332 (1984).

7. A. Y. Rwei et al., Proceedings of the National Academy of Sciences 112, 15719 (December 22, 2015, 2015).

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