Recent developments in d-α-tocopheryl polyethylene glycol-succinate-based nanomedicine for cancer therapy

Abstract

Cancer remains an obstacle to be surmounted by humans. As an FDA-approved biocompatible drug excipient, d-α-tocopheryl polyethylene glycol succinate (TPGS) has been widely applied in drug delivery system (DDS). Along with in-depth analyses of TPGS-based DDS, increasingly attractive results have revealed that TPGS is able to act not only as a simple drug carrier but also as an assistant molecule with various bio-functions to improve anticancer efficacy. In this review, recent advances in TPGS-based DDS are summarized. TPGS can inhibit P-glycoprotein, enhance drug absorption, induce mitochondrial-associated apoptosis or other apoptotic pathways, promote drug penetration and tumor accumulation, and even inhibit tumor metastasis. As a result, many formulations, by using original TPGS, TPGS-drug conjugates or TPGS copolymers, were prepared, and as expected, an enhanced therapeutic effect was achieved in different tumor models, especially in multidrug resistant and metastatic tumors. Although the mechanisms by which TPGS participates in such functions are not yet very clear, considering its effectiveness in tumor treatment, TPGS-based DDS appears to be one of the best candidates for future clinical applications.

Vitamin E D-alpha-tocopheryl polyethylene glycol 1000 succinate-conjugated liposomal docetaxel reverses multidrug resistance in breast cancer cells

“…However, the coumarin‐6‐loaded liposomes were internalized via the cellular endocytosis mechanism, which bypassed the P‐gp mediated drug efflux and enhanced the effects of drug . In addition, TPGS‐coated liposomes resulted in higher cellular uptake due to nonspecific absorbability via absorption‐mediated endocytosis and inhibition of P‐gp efflux by TPGS …”

“…Drug efflux transporters, such as P‐gp, on the cytomembrane of MDR cancer cells actively pump out drugs, resulting in a reduction in intracellular drug accumulation and a poor therapeutic effect . Recently, it was shown that TPGS effectively inhibited the overexpression of P‐gp . Consequently, TPGS‐conjugated liposomes may also contribute to the inhibition of P‐gp.…”

“…[33] In addition, TPGS-coated liposomes resulted in higher cellular uptake due to nonspecific absorbability via absorptionmediated endocytosis and inhibition of P-gp efflux by TPGS. [18,34]…”

“…[35] Recently, it was shown that TPGS effectively inhibited the overexpression of P-gp. [34] Consequently, TPGS-conjugated liposomes may also contribute to the inhibition of P-gp. Based on these findings, we further assessed the effect of TPGS-coated liposomes on drug accumulation in MCF-7/ADR cells.…”

Triphenylphosphonium and D-α-tocopheryl polyethylene glycol 1000 succinate-modified, tanshinone IIA-loaded lipid-polymeric nanocarriers for the targeted therapy of myocardial infarction

“…[13][14][15] As an US FDA-approved biocompatible excipient, TPGS is widely used in nanocarriers for cancer therapy. 16 TPP and TPGS conjugate could combine both advantages and was synthesized for the first time in this study.…”