Rwei Alina Y, Lee Jung-Jae, Zhan Changyou, Liu Qian, Ok Meryem T, Shankarappa Sahadev A, Langer Robert, Kohane Daniel S
Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15719-24. doi: 10.1073/pnas.1518791112. Epub 2015 Dec 7.
Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has ultrapotent local anesthetic properties. They were made photo-labile by encapsulation of a NIR-triggerable photosensitizer; irradiation at 730 nm led to peroxidation of liposomal lipids, allowing drug release. In vitro, 5.6% of TTX was released upon NIR irradiation, which could be repeated a second time. The formulations were not cytotoxic in cell culture. In vivo, injection of liposomes containing TTX and the photosensitizer caused an initial nerve block lasting 13.5 ± 3.1 h. Additional periods of nerve block could be induced by irradiation at 730 nm. The timing, intensity, and duration of nerve blockade could be controlled by adjusting the timing, irradiance, and duration of irradiation. Tissue reaction to this formulation and the associated irradiation was benign.
如果有一种制剂能够在患者期望的时间提供所需强度和持续时间的局部麻醉，那么疼痛管理将得到极大改善。为此，我们开发了近红外（NIR）光触发脂质体，以提供按需可调的局部麻醉。脂质体中含有具有超高效局部麻醉特性的河豚毒素（TTX）。通过包裹一种近红外可触发的光敏剂，使它们对光敏感；730nm的照射导致脂质体脂质过氧化，从而使药物释放。在体外，近红外照射后5.6%的TTX被释放，且可重复进行第二次释放。这些制剂在细胞培养中无细胞毒性。在体内，注射含有TTX和光敏剂的脂质体可引起初始神经阻滞，持续时间为13.5±3.1小时。730nm的照射可诱导额外的神经阻滞期。通过调整照射的时间、辐照度和持续时间，可以控制神经阻滞的时间、强度和持续时间。该制剂及相关照射对组织的反应是良性的。
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