Thesis

Preparation and evaluation of tumour-targeted delivery systems for tocotrienol

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Awarding institution
  • University of Strathclyde
Date of award
  • 2010
Thesis identifier
  • T12756
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Abstract
  • Tocotrienol, a group of compounds present in vitamin E, has gained much attention in recent years for its tumour suppressive properties on cancer cells. However, its therapeutic potential was hampered by the limited ability to reach tumours specifically after intravenous administration. In this study, we aim to develop a formulation of tocotrienol that could be specifically delivered to tumours upon intravenous administration through the use of a tumour-targeted delivery system. Transferrin is an iron transporter whose receptors are often over-expressed in cancer cells due to high iron demand for tumour growth. Conjugation of transferrin to drug delivery systems appeared to be an attractive tool for selective receptor-mediated tumour delivery of therapeutic drugs. The objectives of this study are therefore (1) to prepare and characterize transferrin-bearing vesicles encapsulating tocotrienol and (2) to evaluate in vitro and in vivo the therapeutic and targeting efficacies of this therapeutic system. This work corresponds to the first preparation of a tumour-targeted delivery system able to encapsulate tocotrienol. The grafting of transferrin to tocotrienol-loaded vesicles demonstrated an improved therapeutic efficacy of tocotrienol to at-least 15-fold compared to free tocotrienol in vitro. Intravenous administration of tocotrienol therapeutic systems led to significant tumour regression and improvement in animal survival in murine xenograft models without visible toxicity. In conclusion, our findings showed that tocotrienol encapsulated in transferrin-bearing vesicles is a highly promising therapeutic system, leading to possible eradication of tumours as a result of significant improvement in tocotrienol therapeutic efficacy.
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Note
  • This thesis was previously held under moratorium from 9th May 2011 until 9th May 2013.
DOI
Date Created
  • 2010
Former identifier
  • 821631

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