Plant-derived phytonutrients have emerged as health enhancers. Tocotrienols from the vitamin E family gained high attention in recent years due to their multi-targeted biological properties, including lipid-lowering, neuroprotection, anti-inflammatory, antioxidant, and anticancer effects. 

Anti-cancer agent

Despite clear mechanism of action as an anti-cancer agent, their clinical use is hampered by poor pharmacokinetic profile and low oral bioavailability . Delivery systems based on nanotechnology were proven to be advantageous in elevating the delivery of tocotrienols to tumor sites for enhanced efficacy.

To date, preclinical development of nanocarriers for tocotrienols include niosomes, lipid nanoemulsions, nanostructured lipid carriers (NLCs) and polymeric nanoparticles. Active targeting was explored via the use of transferrin as targeting ligand in niosomes. In vitro, nanocarriers were shown to enhance the anti-proliferative efficacy and cellular uptake of tocotrienols in cancer cells.

 In vivo, improved bioavailability of tocotrienols was reported with NLCs while marked tumor regression was observed with transferrin-targeted niosomes. In this review, the advantages and limitations of each nanocarrier were critically analyzed.

Furthermore, many key challenges were identified including scale-up production, biological barriers, and toxicity profiles. To overcome these challenges, three research opportunities were highlighted based on rapid advancements in the field of nanomedicine.

This review aims to provide a wholesome perspective for tocotrienol nanoformulations in cancer therapy directed toward effective clinical translation.

Regulatory Guidelines

Based on CMC approach, regulatory measures on a global scale are playing important roles in the control mechanism of nanomedicines. Many technical specifications published from ISO nanotechnology technical committee 229 described standardized methods for characterization of nanoformulations.

From the industry’s perspective, there was a pressing need on FDA guidelines due to the lack of convergent definition of “nanoscale.” In 2014, FDA published three instructions on the human use of nanomedicine.

Working in synchronicity, the NCL was formed in 2004 and has since conducted studies on more than 300 nanoformulations Another laboratory in Europe, NCL is offering similar partnerships with scientists and pharmaceutical companies. With these regulations in place, early consultation was made possible where research design can be structured toward regulatory clearance as one of the steps for efficient clinical translation.

This review, nanotechnology was proven to be an efficient tool in enhancing the delivery and efficacy of tocotrienols. When delivered in nanoformulations, tocotrienols showed more than 10-fold improvement in their anti-proliferative efficacy while animal studies reported up to 60% of complete tumor disappearance using tumor-targeted nanocarriers.