**6.5 Ultrasound guided drug delivery**

Ultrasound facilitated drug penetration through brain barriers is yet another option for safe and reversible targeted drug delivery [72]. In this technique, ultrasound radiations are employed to generate shear stress on the vascular endothelium for a transient and reversible perforation in the BBB which facilitates the nanoscaled drug delivery to the targeted site. It appeared in a research outcome that docosahexaenoic acid binding with low-density lipoprotein NPs can penetrate the BBB by the application of ultrasound sonication. A near IR fluorescent dye examination revealed about 60 times greater accumulation of sonication facilitated drug delivery to the targeted site. The main advantage reported was lack of cytotoxicity or neuronal damage due to pointed ultrasound irradiation [73]. PEGylated PLA nanoparticles delivery to the brain was facilitated via ultrasound-induced perforation. β-specific antibody 6E10 was conjugated on PEG-PLA along with the coumarin 6 and DiR as fluorescent probes to assess the target site accumulation. Ultrasonication facilitated NPs penetration was about 2.5-fold more than the complementary non-sonicating therapy [74]. Ultrasound techniques can be used to aid the enhanced delivery of PEG-b-poly(l-Lysine) coupled with siRNA into glioma cells by 10-fold in conjunction with a newer gas-cored nanobubble [75].
