Targeted drug delivery for treatment and imaging of glioblastoma multiforme

Jill M. Stukel, Michael Caplan

Research output: Contribution to journalReview article

13 Scopus citations

Abstract

Glioblastoma multiforme is a grade IV astrocytic tumor with a very high mortality rate. Although current treatment often includes surgical resection, this rarely removes all primary tumor cells, so is usually followed by radiation and/or chemotherapy. Remaining migratory tumor cells invade surrounding healthy tissue and contribute to secondary and tertiary tumor recurrence; therefore, despite significant research into glioma removal and treatment, prognosis remains poor. A variety of treatment modalities have been investigated to deliver drug to these cells, including systemic, diffusive and convection-enhanced delivery (CED). As systemic delivery is limited by molecules larger than ~ 500 Da being unable to cross the blood-brain barrier (BBB), therapeutic concentrations are difficult to attain; thus, localized delivery options relying on diffusion and CED have been used to circumvent the BBB. Although CED enables delivery to a greater volume of tissue than diffusive delivery alone, limitations still exist, requiring that these delivery strategies be improved. This review enumerates the strengths and weaknesses of these currently used strategies and details how predictive mathematical modeling can be used to aid investigators in optimizing these Glioblastoma multiforme is a grade IV astrocytic tumor with a very high mortality rate. Although current treatment often includes surgical resection, this rarely removes all primary tumor cells, so is usually followed by radiation and/or chemotherapy. Remaining migratory tumor cells invade surrounding healthy tissue and contribute to secondary and tertiary tumor recurrence; therefore, despite significant research into glioma removal and treatment, prognosis remains poor. A variety of treatment modalities have been investigated to deliver drug to these cells, including systemic, diffusive and convection-enhanced delivery (CED). As systemic delivery is limited by molecules larger than ~ 500 Da being unable to cross the blood-brain barrier (BBB), therapeutic concentrations are difficult to attain; thus, localized delivery options relying on diffusion and CED have been used to circumvent the BBB. Although CED enables delivery to a greater volume of tissue than diffusive delivery alone, limitations still exist, requiring that these delivery strategies be improved. This review enumerates the strengths and weaknesses of these currently used strategies and details how predictive mathematical modeling can be used to aid investigators in optimizing these delivery modalities for clinical application.

Original languageEnglish (US)
Pages (from-to)705-718
Number of pages14
JournalExpert Opinion on Drug Delivery
Volume6
Issue number7
DOIs
StatePublished - Jul 1 2009

Keywords

  • Convection enhanced delivery
  • Drug delivery
  • Glioblastoma
  • Molecular targeting

ASJC Scopus subject areas

  • Pharmaceutical Science

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