# PolySorbate-Based Drug Formulations for Brain-Targeted Drug Delivery and Anticancer Therapy
## 3 PS-Based Formulations for Various Routes of Drug Administration
### PS-Based Formulations for Oral Delivery  
Intestine, brain, liver, placenta, kidney, and cancer tissues express ATP-binding cassettes and solute carrier transporters (e.g., P-gp, MDR1, and ABCB1) [84,85]. These membrane transport proteins avoid the uptake of toxins and xenobides from the cells and maintain the bioavailability of active drug ingredients [86]. Previous studies have demonstrated that PS-based formulations enhance the intestinal absorption and bioavailability of drugs by modulating membrane transport proteins [87,88] and etoposide [89,90]. To improve the bioavailability of erythromycinocin for an in vivo fish model, three types of microemulsified erythromycinomic formulations were prepared and administered to fish over seven consecutive days. The results showed that emulsified erythromycinocin improved oral bioavailability and achieved a higher therapeutic plasma concentration than erythromycinomic powder [91]. Salmon calcitonin has low bioavailability and stability in the gastrointestinal tract [92]. PS-based microemulsions containing salmon calcitonin improved its oral bioavailability as well as pharmacological activity compared to those of free drugs [92]. The oral bioavailability of curcumin is poor owing to its low aqueous solubility, alkaline instability, and rapid elimination. Curcumin was encapsulated into ionic-gelated alginate-PS 80 nanoparticles (NPs) to increase its oral bioavailability. In healthy human volunteers, administration of the NPs showed five-fold higher bioavailability and higher plasma concentrations of curcumin than administration of curcumin suspensions [93]. Figure 3: Chemical structures of niosome components (DOTMA: 1,2-di-O-octadecenyl-3-trimethylammonium propane, HLB: Hydrophilic lipophilic balance). Reproduced with permission from Reference [73]. Copyright 2018, Elsevier B.V.  
9-Nitrocapntothecin (9-NC) is a potent topoisomerase I inhibitor for the treatment of pancreatic cancer. However, its bioavailability after oral administration is poor. To address the low bioavailability of 9-NC, 9-NC microemulsions were prepared using a self-microumslifying drug delivery system (SMEDDS). Different types of SMEDDS formulations of 9-NC were prepared using ethyl oleate as an oil phase, cremophor EL or PS 80 as a surfactant, and PEG-400/ethanol as cosurfactants. The antitumor effects of the resulting microemulsions were evaluated against human ovarian cancer cells in vitro and in vivo. In SKOV-3 cells, PS 80-based nanoemulsions showed the most efficient growth inhibition. Orally administered PS 80-based nanoemulsions also showed efficient tumor growth suppression in mice bearing human ovarian cancer xenografts [94]. Rosuvastatin is a prescription medicine used to prevent cardiovascular diseases. Microemulsion formulations were used to improve the oral bioavailability of rosuvastatin calcium. The microemulsion of rosuvastatin calcium was prepared using a mixture of peceol oil, PS 20 as a surfactant, and transcutol as a cosurfactant. Stability studies showed that the emulsion was stable for at least 3 months, with a high drug encapsulation efficiency of 91.6%. The microemulsion increased the oral bioavailability of rosuvastatin calcium by increasing the effective surface area of drug exposure in the physiological medium [95]. Fenofibrrate is a lipid-regulating agent that controls the levels of cholesterol and triglycerides (fatty acids) in the blood. A fenofibrrate-loaded emulsion was formulated by mixing olive oil, surfactants (a mixture of PS 20 and PS 80), and distilled water; a small-sized emulsion was prepared with a 5% olive oil concentration, and the mixture of PS 20 and PS 80 at 1:2 ratios showed high fenofibrrate solubility [96]. The formulations were physically stable for up to 4 weeks, with no significant change in particle size. In contrast to the limited dissolution rate of the drug, the SMEDDS formulation showed effective and rapid drug release.