Highly site-selective transvascular drug delivery by the use of nanosecond pulsed laser-induced photomechanical waves

Photomechanical waves (PMWs), which were generated by irradiation of a light-absorbing material (laser target) with nanosecond laser pulses, were used for targeted transvascular drug delivery in rats. An Evans blue (EB) solution was injected into the tail vein, and laser targets were placed on the skin, muscle and brain. Each laser target was irradiated with a laser pulse(s) and 4 h later, the rat was perfused and the distribution of EB fluorescence in the targeted tissues was examined. We observed laser fluence-dependent and hence PMW pressure-dependent extravasation of EB selectively in the tissues that had been exposed to a PMW(s). Uptake of leaked EB into cells in extravascular space was also observed in the targeted tissues. Tissue damage or hemorrhage was not apparent except in the brain exposed to the highest laser fluence used. The results for the brain indicated opening of the blood-brain barrier (BBB). Reverse-order (PMW application before EB injection) experiments showed that the BBB was closed in the duration from 8 h to 12 h after PMW application at a laser fluence of 0.5 J/cm². Since EB molecules are strongly bound with serum albumin in blood, the results indicate that the present method can be applied not only to small molecules but also to macromolecules.