**8. Conclusion**

*Pharmaceutical Formulation Design - Recent Practices*

ing genes and hydrophobic therapeutic agents [65].

**6.4 Other parenteral routes**

**6.5 Ultrasound guided drug delivery**

and the release of DOX to the nucleus, which ultimately decreased the miR-21 expression. This combined DOX and miR-21i delivery surprisingly displayed an antiproliferative efficiency compared with separate treatment of DOX or the miR-21. The outcomes revealed that this co-polymeric system was a better option for deliver-

Delivering the drug directly into the brain is another way of treating brain disorders. This local drug delivery has been approved by the US FDA [66].

Intrathecal administration of nanopharmaceuticals delivers the nano-drugs in the CSF. However, this route of administration is most commonly used for anesthetics and neurotic pain [67]. This route is under experimental phases in humans. It includes two different ways of delivering the therapeutic moiety, either by infusion in the intralumbar region or intraventricularly using an Ommaya reservoir placed subcutaneously and connected to the brain with a catheter [68]. Thioflavin-T was delivered by intrahippocampal injection for targeting the β amyloid in the brain using the nanoparticles. The data reported localization of thioflavin-T in the intracellular and extracellular spaces of the brain, which prevented the formation of β-amyloid aggregates in the Alzheimer's disease. This same method can be adapted to deliver the anticancerous drugs as well as other analgesic peptides [69]. In an *in situ* perfusion study conducted on mice, Polysorbate 80 coated PBCA NPs loaded with the tubocurarine were able to cross the BBB after intraventricular drug administration. There was a marked effect on the EEG epileptiform spikes [70]. Intraarterial drug delivery has an advantage over the other conventional systems of drug delivery because of the increased dose delivery at the desired site of the brain. This route can also be exploited for the immun0-targeting. However, this route has some limitations like a dilution of the drug because of cerebral blood flow [71].

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].

Another targeted approach to the brain for delivering drugs is through the ocular route. The ocular route has so many advantages like reduced peripheral toxicity and

**7. Future prospects for nanopharmaceuticals delivery**

**130**

Brain-targeted drug delivery is a difficult matter due to anatomic and pathophysiological brain barriers. The current advances in nanotechnology provide a solution in the form of nanopharmaceuticals, drug containing nanocarriers, to cross the CNS barriers and to target the brain tissue in various disorders. Nanopharmaceuticals' mode of administration into the body is an important aspect, which ultimately effects drug concentration in the brain and drug therapeutic effect. Current chapter highlighted the routes of administration through which nanopharmaceuticals can be delivered to reach the brain. Every route has pros and cons, nanopharmaceuticals overcome the route associated limitations in the delivery of drug to the brain due to their peculiar physicochemical properties and surface modulation. Translation this research area into the clinic still require investigations, as safety is the foremost concern and distribution to other body organs must be eradicated. Moreover, there is a need to control the drug delivery rate when nanopharmaceuticals reach the brain for safer action.
