# PolySorbate-Based Drug Formulations for Brain-Targeted Drug Delivery and Anticancer Therapy
## 5 PS-Coated NPs for Efficient BBB Transport
The nanoformulation coated with PS-80 crossed the BBB through the endocytosis pathway and inhibited the P-gp efflux pump to avoid drug elimination [140]. PS 80-coated particles showed higher anticancer efficacy than free drugs or PS 80-free formulations. [PERSON]'s disease-induced albino mice were treated with PS 80-coated PLGA NPs encapsulating thymoquinone [141]. These NPs enhanced the bioavailability of thymoquinone, reduced the immobility time (\(39.45\pm 3.32\) s), and increased superoxide dismutase functioning (\(8.33\pm 2.61\) units/mg) upon injection into mice (\(5\) mg/kg concentrations). Thymoquinone reduced oxidative stress and thus restricted the accumulation of A\(\beta\) and hyperphosphorylated \(\tau\)-protein tangles via the antioxidant cascade [141]. PS 80-coated PLGA NPs were developed for the efficient transport of small interfering RNA (siRNA) across the BBB in traumatic brain injury (TBI) [142] (Figure 10). siRNA-based therapeutics can mitigate disease progression in TBI treatment, but siRNA suffers from poor BBB transport. The surface of siRNA-loaded PLGA NPs was coated with five different coating materials (e.g., PS 80, Pluronic F-68, DSPE-PEG, DSPE-PEG-glutathione (GSH), DSPE-PEG-transferrin (Tf)) to identify a surface coating material and coating density that can maximize the penetration of siRNA-loaded NPs across intact BBB. Among the NPs with different coatings materials, PS-coated NPs showed the most efficient in vitro gene silencing efficiency and BBB penetration. As a result, tau siRNA-loaded PS 80-coated PLGA NPs  
Figure 8: (**A**) PS-coated superparamagnetic iron oxide NPs (PS-SPIONs) pass through the intact BBB in rats under magnetic field. (**B**) Intracellular distribution of the PS-SPIONs in the frontal cortex in the presence of EMF. (i, ii) TEM images of PS-SPIONs that enter the brain by crossing BBB. (iii) Nanoparticle clusters were found near the axons of neurons. (iv) EDS analysis of electron-dense black clusters indicates the presence of Fe. Reproduced with permission from Reference [137]. Copyright 2016, American Chemical Society. significantly suppressed tau expression in cultured primary neural cells. Additionally, they achieved efficient tau silencing in TBI mice with no systemic toxicity when administered during the early or late injury period [142]. Figure 10: Schematic illustrating the design and mechanism of BBB pathophysiology–independent delivery of siRNA in TBI using siRNA-loaded PLGA NPs. Various siRNA-loaded PLGA NPs with five different surface coating materials (e.g., PS 80, Pluronic F-68, DSPE-PEG, DSPE-PE G-GSH, and DSPE-PEG-transferrin (DSPE-PEG-Tf)) and different coating densities were prepared. The gene silencing efficiency and BBB permeability of siRNA-loaded PLGA NPs with various surface coatings were assessed in TBI mice when administered during early injury or late injury periods, corresponding to physically breached BBB and intact BBB, respectively. Upon neuronal uptake of NPs, siRNA is released and silences the harmful proteins involved in TBI pathophysiology. Reproduced with permission from Reference [142]. Figure 9: BBB crossing mechanism of PS 80-coated PLGA NPs loaded with methotrexate-transferrin prodrug conjugates. Redrawn and reproduced with permission from Reference [140].