Ardipusilloside I (ADS-I) is a natural compound that can be isolated from the Chinese medicinal herb Ardisiapusilla A.DC, and has been reported to inhibit the growth of
glioblastoma cells in cultures. This study was designed to test its efficacy by the delivery using
biodegradable implants against
glioblastoma in vivo. ADS-I was incorporated into
polymer microspheres, which were prepared by a mixture of
poly (D, L-lactic acid) and
poly (D, L-lactic-co-glycolic acid)
polymers and then fabricated into wafers. The anti-
glioma activities of ADS-I-loaded wafers were examined by methylthiazol tetrazolium (MTT) assay in cultured rat C6
glioma cells, and by magnetic resonance imaging (MRI) and survival monitoring in C6
glioma-bearing rats. Here, we showed that ADS-I-loaded wafers sustained ADS-I release in vitro for 36 days in Higuchi model of kinetics, and had the same cytotoxic activity as ADS-I in the
solution against the growth of C6
glioma cells in cultures. In C6
glioma-bearing rats, ADS-I wafer implants inhibited
tumor growth in a dose-dependent matter, and were more effective than the same dosage of ADS-I in the
solution. The
tumor suppression efficacies of ADS-I wafer implants were positively correlated with an increase in
tumor cell apoptosis and prolonged animal survival, and were associated with a decrease in
vascular endothelial growth factor, C-reactive
protein,
tumor necrosis factor-α and
interleukin-6, and an increase in
interleukin-2 expression. In conclusion, this study demonstrates significant efficacy of local delivery of ADS-I using
polymer implants against
glioma tumor growth in vivo, suggesting the potential of ADS-I-loaded wafers for
glioma treatment.