title: Concurrent delivery of carmustine, irinotecan, and cisplatin to the cerebral cavity using biodegradable nanofibers: In vitro and in vivo studies.
abstract: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and the prognosis of patients afflicted with GBM has been dismal, exhibiting progressive neurologic impairment and imminent death. Even with the most active regimens currently available, chemotherapy achieves only modest improvement in the overall survival. New chemotherapeutic agents and novel approaches to therapy are required for improving clinical outcomes. In this study, we used an electrospinning technique and developed biodegradable poly[(d,l)-lactide-co-glycolide] nanofibrous membranes that facilitated a sustained release of carmustine (or bis-chloroethylnitrosourea, BCNU), irinotecan, and cisplatin. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vitro and in vivo release behaviors of pharmaceuticals from the nanofibrous membranes. The experimental results showed that the biodegradable, nanofibrous membranes released high concentrations of BCNU, irinotecan, and cisplatin for more than 8 weeks in the cerebral cavity of rats. A histological examination revealed progressive atrophy of the brain tissues without inflammatory reactions. Biodegradable drug-eluting nanofibrous membranes may facilitate sustained delivery of various and concurrent chemotherapeutic agents in the cerebral cavity, enhancing the therapeutic efficacy of GBM treatment and preventing toxic effects resulting from the systemic administration of chemotherapeutic agents.
authors.affiliation: Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuan-Yun
authors.initials: YY
authors.lastname: Tseng
authors.affiliation: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chen-Hsing
authors.initials: CH
authors.lastname: Su
authors.affiliation: Department of Neurosurgery, Taichung Tzu Chi General Hospital, The Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.
authors.forename: Tao-Chieh
authors.initials: TC
authors.lastname: Yang
authors.affiliation: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Tzu-Min
authors.initials: TM
authors.lastname: Chang
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Kau
authors.affiliation: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan. Electronic address: shihjung@mail.cgu.edu.tw.
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002330:Carmustine / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D005909:Glioblastoma / Q000188:drug therapy; D066298:In Vitro Techniques; D000077146:Irinotecan; D057139:Nanofibers; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D000077146:Irinotecan; D002945:Cisplatin; D002330:Carmustine; D002166:Camptothecin
keywords: BCNU; Cisplatin; Glioblastoma multiforme (GBM); Irinotecan; Nanofiber; PLGA