Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes

Abstract

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.pain | site 1 sodium-channel blocker | photosensitizer | light | near infrared

Multiply repeatable and adjustable on-demand phototriggered local anesthesia

“…1,4,8,11,15,18,22,25-octabutoxyphthalocyaninato-palladium(II) (PdPC(OBu) 8 ) [PS] was synthesized as reported [14]. 1,4,8,11,15,18,22,25-octabutoxy-29H,31H-phthalocyanine (Aldrich) was dissolved in anhydrous dimethylformamide and mixed with PdCl 2 (Aldrich) in a 1:3 molar ratio.…”

“…Liposomes were prepared following a thin film hydration method [14]. 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC, Avanti Polar Lipids), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC, Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DSPG, Genzyme), and cholesterol (Sigma) in the molar ratio 3:3:2:3 were dissolved in a chloroform:methanol 9:1 solution.…”

Near-Infrared Light Triggered Release of Molecules from Supramolecular Hydrogel-Nanorod Composites

“…Stimuli-responsive materials are evolving as 'smart' delivery systems where the release of encapsulated molecules is controlled through external triggers, which may be in response to the physiological environment (e.g., enzymes) [2,3] or through sensitivity to an externally applied stimulus [4][5][6][7][8][9]. In the cases of material systems where an external cue is desired, triggers including ultrasound [10], light [4,6,9] and magnetic fields [7,8] have enabled noninvasive modulation of therapeutic payload delivery.…”

“…In the cases of material systems where an external cue is desired, triggers including ultrasound [10], light [4,6,9] and magnetic fields [7,8] have enabled noninvasive modulation of therapeutic payload delivery. In particular, light offers an accessible trigger with high spatiotemporal control, and near-infrared (NIR) light is especially attractive due to its minimal absorbance in vivo when compared with shorter wavelengths [11,12].…”

“…NIR photons can interact with photosensitive molecules and particles to trigger photochemical reactions [9] or to generate heat by the photothermal effect [4,[15][16][17][18]. Thus, the inclusion of gold nanoparticles (e.g., gold nanorods or AuNRs), which interact with NIR light, in materials allows plasmonic heating in response to NIR illumination.…”