Targeted concurrent and sequential delivery of chemotherapeutic and antiangiogenic agents to the brain by using drug-loaded nanofibrous membranes

Yuan Yun Tseng, Tao Chieh Yang, Yi Chuan Wang, Wei Hwa Lee, Tzu Min Chang, Yi Chuan Kau, Shih Jung Liu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Glioblastoma is the most frequent and devastating primary brain tumor. Surgery followed by radiotherapy with concomitant and adjuvant chemotherapy is the standard of care for patients with glioblastoma. Chemotherapy is ineffective, because of the low therapeutic levels of pharmaceuticals in tumor tissues and the well-known tumor-cell resistance to chemotherapy. Therefore, we developed bilayered poly(D,L)-lactide-co-glycolide nanofibrous membranes that enabled the sequential and sustained release of chemotherapeutic and antiangiogenic agents by employing an electrospinning technique. The release characteristics of embedded drugs were determined by employing an in vitro elution technique and high-performance liquid chromatography. The experimental results showed that the fabricated nanofibers showed a sequential drugeluting behavior, with the release of high drug levels of chemotherapeutic carmustine, irinotecan, and cisplatin from day 3, followed by the release of high concentrations of the antiangiogenic combretastatin from day 21. Biodegradable multidrug-eluting nanofibrous membranes were then dispersed into the cerebral cavity of rats by craniectomy, and the in vivo release characteristics of the pharmaceuticals from the membranes were investigated. The results suggested that the nanofibrous membranes released high concentrations of pharmaceuticals for more than 8 weeks in the cerebral parenchyma of rats. The result of histological analysis demonstrated developmental atrophy of brains with no inflammation. Biodegradable nanofibrous membranes can be manufactured for long-term sequential transport of different chemotherapeutic and antiangiogenic agents in the brain, which can potentially improve the treatment of glioblastoma multiforme and prevent toxic effects due to systemic administration.

Original languageEnglish
Pages (from-to)1265-1276
Number of pages12
JournalInternational Journal of Nanomedicine
Volume12
DOIs
Publication statusPublished - Feb 14 2017

Keywords

  • Antiangiogenesis
  • Chemotherapy
  • Glioblastoma multiforme (GBM)
  • Nanofibrous membrane
  • Poly(D,L)-lactide-co-glycolide (PLGA)
  • Targeted therapy

ASJC Scopus subject areas

  • Bioengineering
  • Biophysics
  • Biomaterials
  • Drug Discovery
  • Organic Chemistry

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