In vivo performance of implantable biodegradable preparations delivering Paclitaxel and Etanidazole for the treatment of glioma.
Drug-releasing implants delivering chemotherapeutic and radio-sensitizing agents are beginning to play a major role in the post-surgical eradication of residual glioma in the brain. Benefits from early arresting of tumor growth and tumor recovery dynamics stress the impact of drug release profiles of the implants on the efficacy of the treatment. This paper examines responses of BALB/c nude mice, bearing C6 glioma tumors subcutaneously, to treatments by PLGA microspheres, microparticles and discs-delivering Paclitaxel and Etanidazole. The experimental results are used to correlate the efficacy of treatment to in vitro release profiles from the various formulations. Our study demonstrates that radio-sensitizing effects during irradiation could be achieved by double burst profiles from Etanidazole-loaded discs, when compared to controls 17 days after implantation despite the short half-life of Etanidazole (1.4h) in vivo. These results also showed inhibited tumor growth on tumor volumes of 59%, 65% and 70% over the blank placebo groups after 21 days of tumor growth for spray-dried microspheres, electrohydrodynamic atomization microparticles and spray-dried discs, respectively.
Kumar Naraharisetti
Pavan
P
Molecular Engineering of Biological and Chemical Systems, Singapore-MIT Alliance, Singapore 117576, Singapore.
Yung Sheng Ong
Benjamin
B
Wei Xie
Jing
J
Kam Yiu Lee
Timothy
T
Wang
Chi-Hwa
CH
Sahinidis
Nikolaos V
NV
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D017341:Etanidazole / Q000008:administration & dosage*; D005910:Glioma / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D051381:Rats
D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D011838:Radiation-Sensitizing Agents; D017341:Etanidazole; D017239:Paclitaxel