Advanced interstitial chemotherapy combined with targeted treatment of malignant glioma in rats by using drug-loaded nanofibrous membranes
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Yuan-Yun Tseng1,2, Chen-Hsing Su3, Shun-Tai Yang1,2, Yin-Chen Huang4, Wei-Hwa Lee5, Yi-Chuan Wang6, Shou-Cheng Liu6, Shih-Jung Liu6,7
1Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
2Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
3Department of Neurosurgery, Chung Shan Medical University Hospital, Taichung, Taiwan
4Department of Neurosurgery, Chang Gung Memorial Hospital-Chiayi, Chang Gung University College of Medicine, Tao-Yuan, Taiwan
5Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
6Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan
7Department of Orthopedics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
Shih-Jung Liu, email: email@example.com
Keywords: glioblastoma multiforme (GBM), chemotherapy, targeted therapy, nanofiber, antiangiogenesis
Received: March 06, 2016 Accepted: June 27, 2016 Published: August 1, 2016
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.
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