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      TPGS Decorated Liposomes as Multifunctional Nano-Delivery Systems

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          Abstract

          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.

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          Most cited references179

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          Global cancer statistics, 2012.

          Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.
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            PEGylation as a strategy for improving nanoparticle-based drug and gene delivery.

            Coating the surface of nanoparticles with polyethylene glycol (PEG), or "PEGylation", is a commonly used approach for improving the efficiency of drug and gene delivery to target cells and tissues. Building from the success of PEGylating proteins to improve systemic circulation time and decrease immunogenicity, the impact of PEG coatings on the fate of systemically administered nanoparticle formulations has, and continues to be, widely studied. PEG coatings on nanoparticles shield the surface from aggregation, opsonization, and phagocytosis, prolonging systemic circulation time. Here, we briefly describe the history of the development of PEGylated nanoparticle formulations for systemic administration, including how factors such as PEG molecular weight, PEG surface density, nanoparticle core properties, and repeated administration impact circulation time. A less frequently discussed topic, we then describe how PEG coatings on nanoparticles have also been utilized for overcoming various biological barriers to efficient drug and gene delivery associated with other modes of administration, ranging from gastrointestinal to ocular. Finally, we describe both methods for PEGylating nanoparticles and methods for characterizing PEG surface density, a key factor in the effectiveness of the PEG surface coating for improving drug and gene delivery.
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              Liposomal Formulations in Clinical Use: An Updated Review

              Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their biodistribution profile, which further enhances the therapeutic index of various drugs. Extensive research is being carried out using these nano drug delivery systems in diverse areas including the delivery of anti-cancer, anti-fungal, anti-inflammatory drugs and therapeutic genes. The significant contribution of liposomes as drug delivery systems in the healthcare sector is known by many clinical products, e.g., Doxil®, Ambisome®, DepoDur™, etc. This review provides a detailed update on liposomal technologies e.g., DepoFoam™ Technology, Stealth technology, etc., the formulation aspects of clinically used products and ongoing clinical trials on liposomes.
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                Author and article information

                Contributors
                Natalie.Trevaskis@monash.edu
                Journal
                Pharm Res
                Pharm Res
                Pharmaceutical Research
                Springer US (New York )
                0724-8741
                1573-904X
                14 November 2022
                14 November 2022
                : 1-19
                Affiliations
                GRID grid.1002.3, ISNI 0000 0004 1936 7857, Drug Delivery, Disposition and Dynamics, , Monash Institute of Pharmaceutical Sciences, Monash University, ; 399 Royal Parade, Parkville, VIC 3052 Australia
                Article
                3424
                10.1007/s11095-022-03424-6
                9663195
                36376604
                cda76329-9c50-42f7-96c5-355663924547
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 August 2022
                : 23 October 2022
                Funding
                Funded by: Monash University
                Categories
                Review Article

                Pharmacology & Pharmaceutical medicine
                cancer therapy,d-alpha-tocopheryl polyethylene glycol succinate (tpgs), liposomes,drug delivery,pharmacokinetics

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