Abstract
The feasibility of a new chemotherapy of the brain tumor which utilizes the direct transport pathway from the nasal cavity to the cerebrospinal fluid (CSF) was evaluated using three anticancer drugs with small MW, cisplatin analogue pyridoxatodiammineplatinum (II) (P-PtB), mitomycin C (MMC) and methotrexate (MTX). In vitro anticancer activity of MTX against 9L glioma cells was particularly potent compared with P-PtB and MMC. The pharmacokinetic studies following nasal and intravenous applications revealed that P-PtB and MTX, which are relatively hydrophilic, archived significantly high concentration in the CSF following nasal application, while lipophilic MMC was not detected following both nasal and intravenous applications. Therefore, the low lipophilic anticancer drugs are suitable for the strategy. The investigations on the enhancement and duration of the drug concentration in the CSF indicated that the most favorable dosage forms of P-PtB and MTX are nebulization of the powder and instillation of a viscous CMC (carboxymethyl cellulose) solution, respectively. It was also shown that acetazoleamide, which is used clinically to reduce the renal side effect by MTX, enhanced the MTX level in the CSF and reduced the plasma MTX level. The in vivo therapeutic potencies of P-PtB and MTX applied as favorable dosage forms as shown above were evaluated using 9L-bearing animals. Compared with the non-treated animals, P-PtB neither increased the survival nor reduced the tumor weight at the death. On the contrary, the tumor weight of the rats receiving four nasal applications of MTX was significantly reduced as compared to the non-treated group and the intraperitoneal group. It was clarified that efficient chemotherapy of the brain tumor and the reduction of systemic side effects are enabled by nasal application of anticancer agents. Our strategy is thought to be clinically significant.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
