Biodegradable Spray Dried Microspheres and Discs Delivering Paclitaxel and Etanidazole for the Treatment of Giloma: an in Vivo Subcutaneous Study
Benjamin Y. S. Ong, Department of Chemical & Biomolecular Engineering, National University of Singapore / University of Illinois at Urbana-Champaign, 4 Engineering Drive 4, Singapore, Singapore, 117576, Singapore, Pavan Kumar Naraharisetti, MEBCS Program, Singapore-MIT Alliance, 4 Engineering Drive 3, Singapore, 117576, Singapore, Jingwei Xie, Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117576, Singapore, Chi-Hwa Wang, National University of Singapore, Department of Chemical and Biomolecular Engineering, Singapore, 117576, Singapore, and Nick Sahinidis, University of Illinois, Department of Chemical and Biomolecular Engineering, 600 South Mathews Avenue, Urbana, IL 61801.
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, stresses 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 giloma 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. The results demonstrated that radio-sensitizing effects during irradiation could be achieved by double burst profiles from Etanidazole loaded discs to a certain degree, when compared to controls 17 days after implantation despite the short half-life of Etanidazole (1.4 hrs) in vivo. Our study also shows that spray dried Paclitaxel loaded microspheres reduce tumor volume by as much as 77%. When these microspheres were used, tumor growth 27 days after tumor implantation averaged 2.3 cm3 as compared to 9.8 cm3 for the placebo control group.