Codelivery of doxorubicin-containing thermosensitive hydrogels incorporated with docetaxel-loaded mixed micelles enhances local cancer therapy

Ming Thau Sheu, Hua Jing Jhan, Chia Yu Su, Ling Chun Chen, Chia En Chang, Der Zen Liu, Hsiu O. Ho

研究成果: 雜誌貢獻文章同行評審

61 引文 斯高帕斯(Scopus)

摘要

Doxorubicin (DOX) thermosensitive hydrogels (TSHs) incorporated with docetaxel (DOC)-loaded mixed micelles were developed to co-deliver these two drugs through a TSH system, DH700kMF-13.5/M-DocLF, to improve local cancer therapy and reduce side effects. First, Pluronics-based DOC-loaded mixed micelles were developed and optimized. The optimal formulation designated as M-DocLF was composed of 1 mg/g docetaxel, 15 mg/g Pluronic F127 (PF127), and 45 mg/g Pluronic L121 (PL121). Rheological tests showed that DH700kMF-13.5/M-DocLF was an injectable flowing solution, which formed a nonflowing gel at body temperature. After intratumoral (IT) or peritumoral (PT) administration, DH700kMF-13.5/M-DocLF demonstrated efficient growth inhibition of CT-26 tumors in a Balb/c mice model. The tumor inhibitory rate after IT administration of DH700kMF-13.5/M-DocLF was 92.4%, followed by 85.8%, 75.6%, 62.9%, 50.6%, and 49.5% for DH700kMF-15, free DOX, F-13.5/M-DocLF, Tynen (DOC solution), and M-DocLF, respectively. Furthermore, PT administration of DH700kMF-13.5/M-DocLF resulted in similar efficacies. Pharmacokinetic and biodistribution studies showed that after subcutaneous (SC) and IT administration of the designated formulations, smaller amounts of DOX and DOC were absorbed from the local SC or tumor sites into systemic circulation, probably reducing their systemic toxicity. Tumor retention of DOX and DOC in biodistribution studies further revealed that co-delivery of these two drugs in DH700KMF-13.5/M-DocLF potentially enhanced the efficacy of tumor inhibition. In conclusion, our in situ injectable DOX and DOC TSH is a potential dual drug delivery system, which can enhance the efficacy of cancer chemotherapy with minimal side effects and reduced chemoresistance.

原文英語
頁(從 - 到)260-270
頁數11
期刊Colloids and Surfaces B: Biointerfaces
143
DOIs
出版狀態已發佈 - 7月 1 2016

ASJC Scopus subject areas

  • 生物技術
  • 表面和介面
  • 物理與理論化學
  • 膠體和表面化學

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