# PolySorbate-Based Drug Formulations for Brain-Targeted Drug Delivery and Anticancer Therapy
## 1 Introduction  
Drug delivery systems are one of the mainstream strategies for achieving targeted delivery and controlled release of therapeutic drugs in the body. Various drug carriers composed of polymers, dendrimers, metal oxides, hydrogels, cell-derived membranes, exosomes, and surfactants have been developed to improve the therapeutic efficacy of drugs and alter their pharmacokinetics [1]. Despite the several advantages of drug carriers, some drug carriers have limitations, including toxicity, low physicochemical stability, immune responses, poor cell specificity, unwanted drug leakage, and high manufacturing cost, which make them unsuitable for practical applications [2]. Extensive research efforts have been made to develop drug carriers for safe, efficient, and targeted drug delivery by addressing the aforementioned issues [2]. Recently, drug carriers composed of surfactants have garnered great attention owing to their enhanced bioavailability and high biocompatibility [3]. Surfactants have been widely used in pharmaceutical formulations because they can enhance drug solubility and prevent protein aggregation [4]. Nonionic surfactants with charge-free head groups are an important subclass of surfactants. They have been intensively utilized as emulsifiers and stabilizers in the cosmetic industry [5]. Nonionic surfactants are commercially available in various chemical structures. Various types of nonionic surfactants have been used to form emulsions, micelles, and niosomes, all of which can efficiently encapsulate hydrophilic and hydrophobic molecules [6, 7]. The features of nonionic surfactant-based formulations are similar to those of liposomes, and thus, they are suitable alternatives to phospholipids. Low cost, bulk abundance, high physical stability, and ease of storage are advantages of using nonionic surfactants as pharmaceutical formulations. Moreover, the rich phase separation behavior and low critical micellization temperature values are important features of nonionic surfactants that make them attractive for pharmaceutical applications. Polysorbates (PSs), which are commerciallyknown as Tween, are synthetic nonionic surfactants that consist of polyethylene sorbitan fatty acid esters. PSs have numerous advantages, such as commercial abundance and ease of chemical modification, which render them suitable for various biomedical applications. Therefore, PSs have been widely employed as emulsifiers and stabilizers in various drug formulations and food additives [6; 7]. PSs have also served as wetting agents, foaming agents, and dispersants [8; 9; 10; 11]. Recently, various PS-drug conjugates and PS-conjugated drug carriers have been developed for safe and efficient drug delivery [12; 13; 14]. PSs have also attracted great attention as brain-targeting coating materials that can facilitate the transport of drug carriers across the blood-brain barrier (BBB) [15]. This review introduces the general features of PSs and PS-based drug carriers and summarizes recent progress in the development of PS-based drug carriers for the treatment of various diseases. Special emphasis is placed on PS-based drug carriers for brain-targeted drug delivery. In addition, the mechanism of action, current limitations, and perspectives of PS-based drug carriers are presented.