Abstract:
Being an unsaturated form of vitamin E, tocotrienols (T3) has gained popularity due to its antioxidant and anti-cancer properties. Yet, owing to its poor aqueous solubility, the formulation of tocotrienols is often difficult. Moreover, poor oral bioavailability limits the clinical applications of T3. In this case, targeted nanoparticle delivery system serves as an alternative approach to novel formulation of T3, since the sub-micron sized nanoparticles can enhance both the pharmacokinetic and surface properties of T3. Therefore, the aims of this study are to prepare and characterize a tumour-targeted nanoparticulate formulation for T3 delivery to breast cancer cells, and to evaluate the therapeutic efficacy of the delivery system in-vitro and in-vivo. In this study, niosomes were used as nanocarrier to encapsulate tocotrienol. The niosomes was synthesized from non-ionic surfactants using film hydration method, followed by ultra-sonication to reduce its size to nanoscale. The outer surface of niosomes were then conjugated with transferrin (Tf) via chemical linker. Formulations from this study have shown capability in producing spherical niosomes with negative zeta potential value and particle size less than 200nm. The average encapsulation efficiency, drug loading and Tf- conjugation efficiency for Tf-conjugated niosomes were 28.0%, 5.8% and 13.1%, respectively. Meanwhile, higher encapsulation efficiency and drug loading were observed in PEG-niosomes, which were 42.9% and 6.8%, respectively. Anti-proliferative assay showed at least 2-fold enhancement with nano-formulated T3 compared with non-encapsulated T3. When tested in tumour-bearing BALB/c nude mice model, it was found that the transferrin- coupled nisome had the highest cytostatic effect and tumour response in MDA-MB-231 xenograft, followed by PEG-conjugated niosome, and lastly non-encapsulated tocotrienol. This study serves as a platform towards developing a novel product of tocotrienol with enhanced biodistribution profile and evaluated its therapeutic potential of tocotrienol in cancer therapy.
