# PolySorbate-Based Drug Formulations for Brain-Targeted Drug Delivery and Anticancer Therapy
## 6 Anticancer Therapy Using PS-Based Formulations  
Cisplatin is widely used for treating bladder cancer [143; 144]. Because of its high toxicity, direct therapeutic usage is avoided. Cisplatin formulation developed with nonionic surfactants for i.v. administration. The nanoemulsions showed sustained release of the drugs and better activity against bladder cancer cells.  
GEM, a chemotherapeutic agent, has limitations to in vivo cancer therapy owing to its hydrophilic nature. The mixture of Tween 80, Span 80, 0.9 % sodium chloride solution was used to prepare GEM-loaded nanoemulsions [145]. The results showed that the release of GEM at pH 6.5 (45.19%) was higher than that at pH 7.4 (13.62%). The cytotoxicity study showed that the optimized nanoemulsion containing GEM induced cytotoxicity towards A549 cells compared to a control group (i.e., GEM solution).  
Docetaxel (DTX) is a widely used anticancer drug for the treatment of several types of cancers, including metastatic breast cancer, metastatic non-small cell lung cancer, hormone-refractory prostate cancer, gastric adenocarcinoma, and squamous cell carcinoma of the head and neck [146]. DTX-encapsulated, rod-like micelles were fabricated using PS 80 and phospholipids. The size of micelles was 13 nm with narrow size distribution. Pharmacokinetics results suggested that the micelles increased the residence amount of DTX in kidney, spleen, ovary, uterus, heart, and liver. The hemolytic potentials study revealed that the mixed micelles were safe for intravenous injection [147].  
PS-based nanoemulsions were developed for efficient intracellular delivery of photos sensitizers [148]. Indocyanine green (ICG) is a near-infrared light-absorbing dye approved by the FDA [149]. ICG has been employed as an NIR fluorescence-imaging tracer and photosensitizer. ICG was loaded into nanoemulsions composed of cationic lipid stearyamine (SA) and surfactant mixtures of PS 80 and Span 85. Loading ICG into SA-incorporated nanoemulsions more effectively reduced the aggregation and degradation of ICG compared to loading in SA-free nanoemulsions. SA incorporation also enhanced tumor cell uptake of ICG-loaded nanoemulsions due to positive charges of the SA-incorporated nanoemulsions. As a result, compared to SA-free nanoemulsions encapsulating ICG, SA-incorporated nanoemulsions encapsulating ICG exhibited higher phototoxicity upon NIR light irradiation. After subcutaneous injection into the footpad of mice, SA-incorporated nanoemulsions exhibited higher concentrations of ICG in popliteal lymph nodes compared to SA-free nanoemulsions [148].  
PS 80-based micelles were prepared for combination chemo/photothermal/photodynamic cancer therapy via effective intracellular delivery of piperlogumine (PL) and ICG [150] (Figure 11). PL was used as a cancer-specific anticancer agent by inducing selective oxidative stress in cancer cells. ICG was utilized as an NIR light-absorbing photothermal and photodynamic agent. PS 80-based micelles demonstrated successful dual drug encapsulation. The micelle formulations enhanced the cellular uptake, photothermal effects, and photodynamic effects of ICG. ICG-loaded PS 80-based micelles demonstrated NIR light-triggered photothermal and photodynamic effects. ICG- and PL-loaded PS 80-based micelles exhibited cancer-specific cytotoxicity because PL selectively induces oxidative stress in cancer cells. This study confirmed that PL-ICG-T80 micelles are an effective platform to achieve efficient, cancer-targeted chemo-photodynamic combination therapy [150].