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The objective of this study was to develop a combination chemotherapy ofimplantation of a 3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-loaded wafer and intracarotidperfusion of BCNU-loaded nanoparticles for glioma treatment in vivo. BCNU-loadedpoly(D,L-lactic acid) (PLA) nanoparticles coated with transferrin (Tf) were preparedby a solvent evaporation/diffusion method using Tf as the emulsifier. X-ray photoelectronspectroscopy, Bratton-Marshall colorimetric assay and zeta-potential analysisconfirmed the existence of Tf on the nanoparticles and their functional activities.BCNU-loaded PLA wafers were made of BCNU-loaded PLA microspheres. In vitro drugrelease behavior demonstrated that BCNU was released from the Tf-PLA nanoparticlesand wafers in two distinct phases. The biodistribution of Tf-coated nanoparticlesinvestigated by 99mTc-labeled single-photon emission computed tomography (SPECT)showed that the surface-containing Tf-PLA nanoparticles were concentrated in thebrain. Inhibition of tumor growth in the C6 glioma-bearing animal model showedthat combinational chemotherapy of BCNU-loaded wafer and BCNU-loaded PLA nanoparticleshad a stronger inhibitory effect and prolonged the average survival time of rats(164%) compared with that of the control group. Furthermore, the tumors of thistreatment group were not visible by examination at 4 weeks. The results of thisstudy demonstrate for the first time that combination therapy of implantationof a BCNU-loaded wafer and intracarotid perfusion of BCNU-loaded nanoparticlesmay be a new strategy for glioma gene therapy.

oncology reports

Inhibition of C6 glioma in vivo by combination chemotherapy of implantation of polymer wafer and intracarotid perfusion of transferrin-decorated nanoparticles