TPGS Nano Formulation in Triple Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking estrogen receptors, progesterone receptors, and HER2 expression, which limits targeted therapeutic options and contributes to poor clinical outcomes. D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a water-soluble derivative of natural vitamin E, has emerged as a promising nanocarrier due to its amphiphilic nature, ability to enhance drug solubility, inhibit P-glycoprotein (P-gp), and selectively induce apoptosis in cancer cells.

This review explores the physicochemical and pharmacological properties of TPGS and its application as a nanocarrier in TNBC therapy. TPGS induces cytotoxic effects via multiple mechanisms, including P-gp inhibition, reactive oxygen species (ROS) generation, mitochondrial dysfunction, and DNA damage, leading to caspase-dependent and independent cell death. It also enhances the therapeutic efficacy of chemotherapeutic agents by overcoming multidrug resistance.

Furthermore, the paper discusses the molecular heterogeneity and complex signaling pathways involved in TNBC pathogenesis—such as PI3K/AKT/mTOR, Notch, Wnt/β-catenin, and Hedgehog—which offer potential targets for combinatory or synergistic treatment strategies involving TPGS-based nanoformulations. These findings support the role of TPGS as a multifunctional excipient and therapeutic agent in addressing the challenges associated with TNBC treatment.

An overview of vitamin E and TPGS

Tocopherols (TOS) and tocotrienols are two forms of vitamin E, which is a lipophilic material. Human tissues and plasma contain a large amount of the vitamin α-TOS.

This type controls the anti inflammatory and antioxidant characteristics of  cells by inhibiting protein lipoxygenase enzymes. In addition, α-TOS plays a pivotal role in safeguarding the RBC membrane and lung cells from free radicals toxicity [16]. Several α-TOS analogues with increased biocompatibility and anticancer efficacy were readily obtained through chemical modification of the chromanol (head group) and phytyl (tail group) modifications of vitamin E.

An example of the modification is TPGS [α TOS-succinyl-Poly (1–2-oxatride)} iso]ón. PEG, which has chemical formula C33O5H54 (CH2CH2O) n, is used to testerify α TOS succinate. The number “n” indicates how many PEG molecules are joined. TPGS is amphiphilic due to its composition of hydrophilic PEG.and lipophilic α-TOS TPGS has been shown to be safe and non-genotoxic. In many nano formulations developed for tumor therapy, it is the preferred excipient (adjuvant) due to its strong anticancer potential as compared to plain α-TOS.

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Indrajeet Yadav, Priyanka Sonker, TPGS Nano Formulation in Triple Negative Breast Cancer, INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES, [ISSN: 0975-4725; CODEN(USA): IJPS00], Journal Homepage: https://www.ijpsjournal.com, DOI: 10.5281/zenodo.15650192, Indrajeet yadav, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 6, 2464-2477 |Review

See also the interesting video on Vitamin E TPGS below and read more here