Current trends in the use of vitamin E-based micellar nanocarriers for anticancer drug delivery

ABSTRACT

Introduction: Owing to the complexity of cancer pathogenesis, conventional chemotherapy can be an inadequate method of killing cancer cells effectively. Nanoparticle-based drug delivery systems have been widely exploited pre-clinically in recent years.

Areas covered: Incorporation of vitamin-E in nanocarriers have the advantage of (1) improving the hydrophobicity of the drug delivery system, thereby improving the solubility of the loaded poorly soluble anticancer drugs, (2) enhancing the biocompatibility of the polymeric drug carriers, and (3) improving the anticancer potential of the chemotherapeutic agents by reversing the cellular drug resistance via simultaneous administration. In addition to being a powerful antioxidant, vitamin E demonstrated its anticancer potential by inducing apoptosis in various cancer cell lines. Various vitamin E analogs have proven their ability to cause marked inhibition of drug efflux transporters.

Expert opinion: The review discusses the potential of incorporating vitamin E in the polymeric micelles which are designed to carry poorly water-soluble anticancer drugs. Current applications of various vitamin E-based polymeric micelles with emphasis on the use of α-tocopherol, D-α-tocopheryl succinate (α-TOS) and its conjugates such as D-α-tocopheryl polyethylene glycol-succinate (TPGS) in micellar system is delineated. Advantages of utilizing polymeric micelles for drug delivery and the challenges to treat cancer, including multiple drug resistance have been discussed.

KEYWORDS:

• α-Tocopherol succinate
• targeted drug delivery
• multi drug resistance
• apoptosis
• P-glycoprotein
• micelles

Article highlights

• Vitamin E-based nanocarriers were discussed that can entrap or conjugate vitamin E analogs in the polymeric micelles.

• Vitamin E-based nanomedicines (i) improve the aqueous solubility of hydrophobic drugs, (ii) enhance their penetration into the cells, (iii) inhibit drug efflux transporters, including P-gp that increase the intracellular drug concentration, thereby improve the therapeutic efficacy.

• Solubilization ability of vitamin E derivatives has been widely utilized to deliver highly lipophilic chemotherapeutic drugs as well as for combination therapy where multiple poorly soluble chemotherapeutic drugs are loaded.

• Vitamin E and its analogs could disrupt Bcl-xL-Bax interactions, activate Bax, and thus mediate mitochondria-centered apoptotic cancer cell death.

• A PEGylated α-tocopherol derivative, TPGS inhibits ATP-dependent drug efflux transporters, which pumps out chemotherapeutic agent from the cells, thus responsible for lowering the intracellular drug concentration at sub-therapeutic level.

• Environmental stimuli-sensitive bonds between TPGS and the drugs have been introduced in various conjugates for quick liberation of the free drug from the pro-drug following trigger by the environmental stimuli.

This box summarizes key points contained in the article.

Declaration of interest

OM Muddineti is a member of the Indian council of medical research. S Biswas is a member of the Department of Science and Technology (DST) and Department of Biotechnology (DBT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The work was supported in part by the grants provided by the Department of Science and Technology (CS-269/2013), Government of India and Department of Biotechnology (BT/Bio-CARe/07/10003/2013-14), Govt of India to Swati Biswas. Omkara Swami gratefully acknowledges Indian Council of Medical Research (2014-24190), Department of Health Research, Ministry of Health & Family Welfare, Government of India for awarding him with the Senior Research Fellowship (SRF).