- Biomaterials. 2009 Sep;30(27):4743-51. Epub 2009 Jun 5.
The inhibition of glioma growth in vitro and in vivo by a chitosan/ellagic acid composite biomaterial.
Kim S, Gaber MW, Zawaski JA, Zhang F, Richardson M, Zhang XA, Yang Y.
School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN 31863, USA.
study has developed a chitosan-based delivery system to locally
administer ellagic acid for brain cancer treatment. We fabricated
chitosan/ellagic acid composite films with various concentrations of
ellagic acid. In vitro release study was performed by using a UV
spectrophotometer, and enzymatic degradation rate was determined by
analyzing the increased free amino groups. Viability of brain cancer
cells (human U87 glioblastomas and rat C6 glioma cells) was measured
via direct and indirect cell culture on the films by MTS assay.
Caspase-3 activation, Western blot for p53, and anti-angiogenesis
assays were also examined. In the in vivo study, GFP-tagged rat C6
glioma cells were implanted subcutaneously at the right flank region of
nude mice and treatments were initiated by implanting the films
subcutaneously. Tumor growth was evaluated by measuring tumor volume
using a caliper, an ultrasound machine, and an optical imaging system.
The chitosan/ellagic acid composite films were enzymatically degradable
and exhibited a sustained slow release of ellagic acid. These materials
could inhibit the cancer cell growth in an ellagic acid
concentration-dependent manner by inducing apoptosis of cancer cells as
well as suppressing angiogenesis. These materials also significantly
suppressed tumor tissue growth in vivo.