Biodegradable hybrid-structured nanofibrous membrane supported chemoprotective gene therapy enhances chemotherapy tolerance and efficacy in malignant glioma rats

Shih Jung Liu, Tao Chieh Yang, Shung Tai Yang, Ying Chun Chen, Yuan Yun Tseng

研究成果: 雜誌貢獻文章同行評審

6 引文 斯高帕斯(Scopus)

摘要

Chemotherapy is ineffective for treating malignant glioma (MG) because of the low therapeutic levels of pharmaceuticals in tumour tissues and the well-known tumour resistance. The resistance to alkylators is modulated by the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT). O6-benzylguanine (O6-BG) can irreversibly inactivate AGT by competing with O6-methylguanine and has been confirmed to increase the therapeutic activity of alkylators. We developed hybrid-structured poly[(d,l)-lactide-co-glycolide] nanofibrous membranes (HSNMs) that enable the sequential and sustained release of O6-BG and two alkylators (carmustine and temozolomide [TMZ]). HSNMs were surgically instilled into the cerebral cavity of pathogen-free rats and F98 glioma-bearing rats. The release behaviours of loaded drugs were quantified by using high-performance liquid chromatography. The treatment results were compared with the rats treated with intraperitoneal injection of O6-BG combined with surgical implantation of carmustine wafer and oral TMZ. The HSNMs revealed a sequential drug release behaviour with the elution of high drug concentrations of O6-BG in the early phase, followed by high levels of two alkylators. All drug concentrations remained high for over 14 weeks. Tumour growth was slower and the mean survival time was significantly prolonged in the HSNM-treated group. Biodegradable HSNMs can enhance therapeutic efficacy and prevent toxic systemic effects.
原文英語
頁(從 - 到)515-526
頁數12
期刊Artificial Cells, Nanomedicine and Biotechnology
46
發行號Sup 2
DOIs
出版狀態已發佈 - 十一月 5 2018

ASJC Scopus subject areas

  • 生物技術
  • 生物醫學工程
  • 醫藥(雜項)
  • 藥學科學

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