Optimisation of the anti-cancer efficacy of various tocotrienol isomers by entrapment in tumour-targeted vesicles

Tocotrienol is a group of four isomers, found in nature as part of vitamin E. Although known for its anti-cancer activity, its therapeutic use is hampered by its limited ability to specifically reach tumours after intravenous administration. Recently, we demonstrated that tocotrienol-rich fraction entrapped in transferrin-bearing vesicles led to an increased therapeutic efficacy in vitro and in vivo on mice, compared to the drug solution. This formulation may be further improved by entrapping only the most effective tocotrienol isomer within the optimised tumour-targeted vesicles. The objectives of this study are therefore 1) to evaluate the anti-proliferative efficacy of the individual tocotrienol isomers entrapped in transferrin-bearing vesicles in vitro on various cancer cells and 2) to optimise the delivery system by a) increasing the amount of drug entrapped within the vesicles, b) increasing the amount of transferrin grafted to the vesicles and c) modifying the structure of the vesicles. Among all the tested isomers, the highest anti-proliferative efficacy was observed when using α-tocotrienol entrapped within transferrin-bearing unilamellar vesicles, with an efficacy enhanced by at least 175-fold on A431 cells compared to drug solution. Alpha-tocotrienol was also found to be more efficacious than two combinations of the four isomers. The vesicles bearing 12 mg transferrin and entrapping 2 mg α-tocotrienol showed the highest anti-proliferative activity among the tested unilamellar formulations. Further enhanced anti-cancer efficacy was observed when using targeted multilamellar vesicles instead of unilamellar vesicles. Treatments with transferrin-bearing multilamellar and unilamellar vesicles entrapping α-tocotrienol resulted in an increased anti-cancer effect compared to the previously reported vesicles of tocotrienol-rich fraction. In conclusion, our study demonstrated that the anti-cancer efficacy of tocotrienols can be improved by entrapping α-tocotrienol instead of tocotrienol-rich-fraction inside optimised transferrin-bearing vesicles.

Name dc:type.qualificationname

mres

Level dc:type.qualificationlevel

masters-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2013

Author dc:creator

• Karim, Reatul

Advisor dc:contributor.advisor

• Dufès, Christine

DOI

10.48730/gc7j-6744

Identifier

T13654

Author Identifier

201273980

OAI identifier oai:identifier

oai:strathclyde:v118rd63p