# PolySorbate-Based Drug Formulations for Brain-Targeted Drug Delivery and Anticancer Therapy
## 7 Conclusions and Perspectives  
PSs are considered important excipients in pharmaceutical formulations. Several studies and reviews have reported the multimodal use of PSs as solubilizers, emulsifiers, stabilizers, microemulsions, nanosomes, self-assembled micelles, and drug carriers for pharmaceutical applications. In this review, we summarized recent progress in PS-based drug formulations and drug delivery systems. We also summarized various PS-based drug formulations in terms of different routes of administration, such as ocular, transdermal, oral, and nasal delivery. PS was found to be safe and effective for all the administration routes. PSs are used as emulsifiers and solubilizers for hydrophobic drugs and proteins. PS-based drug formulations improve the solubility, stability, and pharmacokinetic properties of drugs, as well as control drug release and drug dissolution rates. In addition, PS can inhibit the P-gp efflux transporter, resulting in increased drug accumulation. Notably, PS-coated drug carriers can cross the BBB via receptor-mediated transcytosis, resulting in brain-targeted drug delivery. The biocompatible nature of PSs is an additional advantage for drug delivery systems. PSs have been widely used in formulations and have demonstrated high therapeutic performance in preclinical studies [3]. In addition to the emulsifying and stabilizing properties, the advantages of using PSs as drug formulation agents are low cost, commercial availability, and ease of handling. Additionally, PSs are relatively low in toxicity, and their characteristic features can be achieved at low concentrations. However, complex mixtures of PSs, lack of spectral/quantitative characterization, and chemical/enzymatic degradation have hampered the use of PSs as active drug formulations. Commercial PSs are heterogeneous mixtures of structurally related compounds. PSs are available in three different grades according to their purities, including multi-compential, super-refined, and ultrapure grades. The multi-compential-grade PS 80 is a mixture of various fatty acid esters, with \(\geq\)58% oleic acid content. In contrast, super-refined and ultrapure PS grades are esterified with at least 98% of their corresponding fatty acids. Ultrapure PS 80 is a highly purified PS that was prepared to meet the standards of Chinese pharmacopeia for human use [151; 152]. Commercial PS 80 contains impurities such as 12-tricosanone, which leads to the occurrence of visible 12-tricosanone particles in drug formulations and decreases the activity of drugs [153]. The impurities of PSs can affect their performance in drug formulations. However, the challenges in characterization of PS heterogeneity have aroused significant interest in the development of new analytical methods to characterize PS heterogeneity. A recent study addressed the limitations in the characterization of PS heterogeneity using high-resolution mass spectrometry (HRMS) [154]. The molecular heterogeneity of PS 80 was analyzed using HRMS coupled with hydrogen/deuterium (H/D) exchange in deuterated methanol. The terminal hydroxyl groups of PSs have labile protons that can undergo H/D exchange in deuterated solvents. The resultant mass shifts indicate structural differences of isomers. Mass variation was identified to predict the structure and heterogeneity of PSs. This method was successfully applied to profile PS 80 samples from different suppliers or of different purity grades [154]. Figure 11: PL- and ICG-loaded PS 80-based NPs for combination chemo/photothermal/photodynamic therapy. Reproduced with permission from Reference [150]. Copyright 2020, Elsevier B.V.  
One of the major concerns involved in PS use is the degradation of PSs. The two main routes of PS degradation are oxidation and hydrolysis [155]. Degradation of PSs leads to protein aggregation, particle formation, lowered efficacy of drugs, and immune responses.