# 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 Ocular Delivery  
Most eye-related problems, including dry eye, fungal infection, inflammation, ocular hypertension, and glaucoma, are generally treated with topical ophthalmic drugs [56]. Ophthalmic drug formulations include nanosomes, micelles, and emulsions; these formulations show high drug-loading efficiency, ocular bioavailability, and prolonged drug effects in the eyes [57]. Compared to other charged surfactants, PSs offer more efficient ocular drug delivery owing to their properties such as smooth penetration, drug-solubilizing capability, and effective drug protection. Moreover, nonionic surfactants are known to be less harmful and irritating than charged surfactants [58]. PSs increase ocular bioavailability because they can act as penetration enhancers that can remove mucus layers and destroy junctional complexes [59].  
DUREZOL(r) is a commercially available corticosteroid formulation used for the treatment of inflammation and pain associated with ocular surgery. This Food and Drug Administration (FDA)-approved formulation contains PS 80 as a nonionic emulsifier (4% \(v/v\)) [60]. Similarly, cyclosporine emulsions containing 1% PS 80 were developed and sold under the brand name Restasis(r) [61]. Many PS-based formulations with various ocular drugs, including flurbiprofen [62], ibuprofen [63], indomethacin [64], dexamethasone [65], chloramphenicol [66], and hydrocortisone [67], have been developed and evaluated in preclinical studies. These PS-based formulations exhibit low irritation, high drug solubility, efficient penetration across cell membranes, and high bioavailability.  
Recently, niosomes composed of cationic lipids and PSs have been developed for nonviral gene delivery. Niosomes are nonionic surfactant-based vesicles formed via self-assembly in an aqueous solution [68; 69]. Niosomes have bilayer structures that can encapsulate both hydrophilic and hydrophobic drugs, such as liposomes. Because niosomes are biodegradable, stable, and inexpensive, they have great potential as alternatives to liposomes [70; 71]. Niosome formulations comprising the cationic lipid \(N\)-[1-(2,3-dioleoyloxy) propyll]-\(N\),\(N\),\(N\)-trimethylammonium chloride (DOTMA) and nonionic PS 60 were developed for retinal gene delivery [72]. The incorporation of natural lipids (i.e., lycopene) resulted in high transfection efficiency in the human retinal pigment epithelial cells (ARPE-19) through the caveolae-mediated endocytic pathway. The DOTMA/PS 60/lipid niosomes administered into the rat retina via subretinal and intravitreal routes efficiently transfected the outer segments of the retina. The same group studied the effects of PS (PS 20, PS 80, and PS 85) on the transfection efficiency of niosomes in the rat retina [73]. The graphical representation of niosomes is shown in Figure 3. Niosomes formulated with PS 20 showed more efficient transfection in retinal cells than the niosomes containing PS 85. The greater hydrophilicity of PS 20-containing niosomes than the PS 85-containing niosomes facilitated caveolae-mediated endocytosis in retinal cells, thereby preventing lysosomal degradation [73].