TPGS Decorated Liposomes as Multifunctional Nano-Delivery Systems

Liposomes are sphere-shaped vesicles that can capture therapeutics either in the outer phospholipid bilayer or inner aqueous core. Liposomes, especially when surface-modified with functional materials, have been used to achieve many benefits in drug delivery, including improving drug solubility, oral bioavailability, pharmacokinetics, and delivery to disease target sites such as cancers. Among the functional materials used to modify the surface of liposomes, the FDA-approved non-ionic surfactant D-alpha-tocopheryl polyethylene glycol succinate (TPGS) is increasingly being applied due to its biocompatibility, lack of toxicity, applicability to various administration routes and ability to enhance solubilization, stability, penetration and overall pharmacokinetics. TPGS decorated liposomes are emerging as a promising drug delivery system for various diseases and are expected to enter the market in the coming years. In this review article, we focus on the multifunctional properties of TPGS-coated liposomes and their beneficial therapeutic applications, including for oral drug delivery, vaccine delivery, ocular administration, and the treatment of various cancers. We also suggest future directions to optimise the manufacture and performance of TPGS liposomes and, thus, the delivery and effect of encapsulated diagnostics and therapeutics.

Introduction

Liposomes are versatile nanocarriers that have gained attention for multiple applications in the drug delivery, cosmetic, and food industries [1,2,3]. Liposomes were the first nano-drug delivery system approved by the United States Food and Drug Administration (FDA) in 1995 when liposomes encapsulating doxorubicin (Doxil®) were approved for ovarian cancer therapy [4]. The FDA has subsequently approved several other liposome-based formulations for cancer therapy, including liposomal formulations of daunorubicin (DaunoXome®) and vincristine (Marqibo®) [5]. Liposomal formulations of amphotericin B (e.g., Ambisome ®) have also proven an important development for the treatment of fungal infections. Liposomes are a new alternative for delivering vaccines such as the products Epaxal ® and Inflexal® V [6].

Liposomes are sphere-shaped vesicles containing a phospholipid bilayer and aqueous core. Hydrophilic molecules can be encapsulated in the aqueous core, whereas lipophilic molecules can be entrapped in the lipid bilayer. Therefore, this lipid-based carrier’s amphiphilic nature is suitable for loading therapeutic agents with a range of physicochemical properties [7]. Liposomes are also generally non-toxic as they are prepared with biocompatible lipids. Importantly, the properties of liposomes, such as their composition, size, surface charge, and modifications, can be purposely modified to control the pharmacokinetics and biodistribution of encapsulated therapeutics and other molecules. This has, in particular, led to the use of liposomes to prolong the half-life and alter the biodistribution of therapeutics. Importantly, this can improve drug safety and efficacy profiles, as has been demonstrated for several important anti-cancer drugs [8].

In the early days of liposome development, conventional liposomes were prepared without significant surface modifications. Early liposomes were associated with various limitations, including instability, inadequate drug loading, rapid drug release, and short blood circulation half-life [9]. The short half-life was found to result from rapid clearance from the blood circulation by the reticuloendothelial system in the liver and spleen following opsonisation (coating of the surface of the liposomes by opsonins in the blood) and subsequent recognition and removal by phagocytic cells [10]. A breakthrough in liposome development in the 1980s was the invention of ‘stealth liposomes’ with a surface coating that prevented opsonisation and phagocytosis, thus significantly prolonging the circulation half-life [11]. The first coating used to prevent opsonisation and prolong circulation half-life was the innovation of modifying liposomes’ surface by adding lipid conjugated polyethylene glycol (PEG) molecules [12].

In addition to PEG, the surface of liposomes has been modified with molecules such as carbohydrates [13], aptamers [14], peptides [15], polysaccharides [16], and vitamins [17]. Mostly these molecules are recognized by surface receptors on specific cells leading to ‘targeted’ delivery. These additions on the surface of liposomes have considerably heightened the application of liposomes in drug delivery, particularly for cancer diagnosis and therapy [18].

An alternate form of PEGylation is the surface modification of liposomes with D-a-tocopheryl PEG 1000 succinate (vitamin E TPGS) [9]. (Fig. 1). As seen for PEG conjugated lipids, surface modification with TPGS can alter the pharmacokinetics (e.g., prolong the circulation half-life) and facilitate enhanced delivery to disease target sites [19,20,21]. In this review, we summarise the general properties of TPGS that make it a valuable molecule for surface engineering of liposomes. We provide an overview of studies demonstrating beneficial therapeutic applications of TPGS decorated liposomes, including to enhance oral and ocular drug delivery, vaccine delivery, and the treatment of various cancers. Finally, we discuss future ways in which TPGS liposomes may be exploited to advance health care.

Download the full article as PDF here TPGS Decorated Liposomes as Multifunctional Nano-Delivery Systems

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Farooq, M.A., Trevaskis, N.L. TPGS Decorated Liposomes as Multifunctional Nano-Delivery Systems. Pharm Res (2022). https://doi.org/10.1007/s11095-022-03424-6

See also the interesting video on Vitamin E TPGS: