TY - JOUR
T1 - Targeted drug delivery for treatment and imaging of glioblastoma multiforme
AU - Stukel, Jill M.
AU - Caplan, Michael
N1 - Funding Information:
The authors thank the Arizona Biomedical Research Commission for funding (ABRC #0707).
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
KW - Convection enhanced delivery
KW - Drug delivery
KW - Glioblastoma
KW - Molecular targeting
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U2 - 10.1517/17425240902988470
DO - 10.1517/17425240902988470
M3 - Review article
C2 - 19538036
AN - SCOPUS:67650378966
SN - 1742-5247
VL - 6
SP - 705
EP - 718
JO - Expert Opinion on Drug Delivery
JF - Expert Opinion on Drug Delivery
IS - 7
ER -