title: Advanced interstitial chemotherapy combined with targeted treatment of malignant glioma in rats by using drug-loaded nanofibrous membranes.
abstract: Glioblastoma multiforme (GBM), the most prevalent and malignant form of a primary brain tumour, is resistant to chemotherapy. In this study, we concurrently loaded three chemotherapeutic agents [bis-chloroethylnitrosourea, irinotecan, and cisplatin; BIC] into 50:50 poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibres and an antiangiogenic agent (combretastatin) into 75:25 PLGA nanofibres [BIC and combretastatin (BICC)/PLGA]. The BICC/PLGA nanofibrous membranes were surgically implanted onto the brain surfaces of healthy rats for conducting pharmacodynamic studies and onto C6 glioma-bearing rats for estimating the therapeutic efficacy.The chemotherapeutic agents were rapidly released from the 50:50 PLGA nanofibres after implantation, followed by the release of combretastatin (approximately 2 weeks later) from the 75:25 PLGA nanofibres. All drug concentrations remained higher in brain tissues than in the blood for more than 8 weeks. The experimental results, including attenuated malignancy, retarded tumour growth, and prolonged survival in tumour-bearing rats, demonstrated the efficacy of the BICC/PLGA nanofibrous membranes. Furthermore, the efficacy of BIC/PLGA and BICC/PLGA nanofibrous membranes was compared. The BICC/PLGA nanofibrous membranes more efficiently retarded the tumour growth and attenuated the malignancy of C6 glioma-bearing rats. Moreover, the addition of combretastatin did not significantly change the drug release behaviour of the BIC/PLGA nanofibrous membranes. The present advanced and novel interstitial chemotherapy and targeted treatment provide a potential strategy and regimen for treating GBM.
authors: Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.|Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Yuan-Yun
authors: YY
authors: Tseng
authors: Department of Neurosurgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors: Chen-Hsing
authors: CH
authors: Su
authors: Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.|Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Shun-Tai
authors: ST
authors: Yang
authors: Department of Neurosurgery, Chang Gung Memorial Hospital-Chiayi, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors: Yin-Chen
authors: YC
authors: Huang
authors: Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Wei-Hwa
authors: WH
authors: Lee
authors: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.
authors: Yi-Chuan
authors: YC
authors: Wang
authors: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.
authors: Shou-Cheng
authors: SC
authors: Liu
authors: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.|Department of Orthopedics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors: Shih-Jung
authors: SJ
authors: Liu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001632:Bibenzyls / Q000378:metabolism; D001921:Brain / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000188:drug therapy*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005038:Ethylnitrosourea / Q000031:analogs & derivatives / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D057139:Nanofibers / Q000737:chemistry / Q000706:statistics & numerical data*; D019635:Neurosurgical Procedures; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D001632:Bibenzyls; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077146:Irinotecan; C040105:combretastatin; D005038:Ethylnitrosourea; D002945:Cisplatin; D002166:Camptothecin
keywords: antiangiogenesis; chemotherapy; glioblastoma multiforme (GBM); nanofiber; targeted therapy