A chitosan/beta-glycerophosphate thermo-sensitive gel for the delivery of ellagic acid for the treatment of brain cancer.
We report here the development of a chitosan/beta-glycerophosphate(Ch/beta-GP) thermo-sensitive gel to deliver ellagic acid (EA) for cancer treatment. The properties of the Ch/beta-GP gels were characterized regarding chemical structure, surface morphology, and viscoelasticity. In vitro EA release rate from the EA loaded Ch/beta-GP gel and chitosan degradation rate were investigated. The anti-tumor effect of the EA loaded Ch/beta-GP gel on brain cancer cells (human U87 glioblastomas and rat C6 glioma cells) was evaluated by examining cell viability. Cell number and activity were monitored by the MTS assay. The Ch/beta-GP solution formed a heat-induced gel at body temperature, and the gelation temperature and time were affected by the final pH of the Ch/beta-GP solution. The lysozyme increased the EA release rate by 2.5 times higher than that in the absence of lysozyme. Dialyzed chitosan solution with final pH 6.3 greatly reduced the beta-GP needed for gelation, thereby significantly improving the biocompatibility of gel (p < 0.001). The chitosan gels containing 1% (w/v) of ellagic acid significantly reduced viability of U87 cells and C6 cells compared with the chitosan gels at 3 days incubation (p < 0.01, and p < 0.001, respectively).
Kim
Sungwoo
S
School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Nishimoto
Satoru K
SK
Bumgardner
Joel D
JD
Haggard
Warren O
WO
Gaber
M Waleed
MW
Yang
Yunzhi
Y
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D055119:Elastic Modulus / Q000187:drug effects; D004610:Ellagic Acid / Q000627:therapeutic use*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005782:Gels / Q000494:pharmacology*; D005994:Glycerophosphates / Q000494:pharmacology*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D009113:Muramidase / Q000378:metabolism; D051381:Rats; D012212:Rheology / Q000187:drug effects; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013997:Time Factors
D005782:Gels; D005994:Glycerophosphates; D012996:Solutions; D004610:Ellagic Acid; D048271:Chitosan; D009113:Muramidase; C031463:beta-glycerophosphoric acid