Delivery of liposome encapsulated temozolomide to brain tumour

Understanding the drug transport for optimisation

W. Zhan (Corresponding Author)

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Temozolomide presents significant anticancer activities in preclinical trials. However, its clinical applications suffer from serious side effects owing to the high concentration in blood and normal tissues. In this study, mathematical modelling is applied to simulate the liposome-mediated delivery of temozolomide under different conditions in a 3-D realistic brain tumour model reconstructed from MR images. Delivery outcomes are evaluated by the bioavailability of free temozolomide across time. As compared to the oral and intravenous administration of free temozolomide, liposome-mediated delivery can successfully improve the drug accumulation in tumour while reducing the drug exposure in blood and normal tissue. Results show that the delivery is less sensitive to the duration of intravenous infusion but highly dependent on the liposome properties. The treatment can be improved by either enhancing the liposome transvascular permeability or using the liposomes with high extracellular release rates. Intravascular release can only increase the risk of adverse effects rather than improving the drug bioavailability in tumour. Results obtained in this study could be applied for optimising the treatment using liposome encapsulated temozolomide.

Original languageEnglish
Pages (from-to)280-292
Number of pages13
JournalInternational Journal of Pharmaceutics
Volume557
Early online date29 Dec 2018
DOIs
Publication statusPublished - 25 Feb 2019

Fingerprint

temozolomide
Brain Neoplasms
Liposomes
Pharmaceutical Preparations
Biological Availability
Intravenous Infusions
Intravenous Administration
Oral Administration
Permeability
Neoplasms

Keywords

  • brain tumour
  • drug transport
  • liposome
  • mathematical model
  • temozolomide

Cite this

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