Novel application of pluronic lecithin organogels (PLOs) for local delivery of synergistic combination of docetaxel and cisplatin to improve therapeutic efficacy against ovarian cancer

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

研究成果: 雜誌貢獻文章

8 引文 斯高帕斯(Scopus)

摘要

The synergistic combination of docetaxel (DTX) and cisplatin (CIS) by local drug delivery with a pluronic lecithin organogel (PLO) to facilitate high drug concentrations at tumor sites and less nonspecific distribution to normal organs is thought to be beneficial in chemotherapy. In this study, using Capryol- 90 (C90) with the addition of lecithin as the oil phase was developed to carry DTX, which was then incorporated into a PLO-containing CIS to formulate a dual-drug injectable PLO for local delivery. An optimal PLO composite, P13L0.15O1.5, composed of PF127:lecithin:C90 at a 13:0.15:1.5 weight ratio was obtained. The sol–gel transition temperature of P13L0.15O1.5 was found to be 33 °C. Tumor inhibition studies illustrated that DTX/CIS-loaded P13L0.15O1.5 could efficiently suppress tumor growth by both intratumoral and peritumoral injections in SKOV-3 xenograft mouse model. Pharmacokinetic studies showed that subcutaneous administration of P13L0.15O1.5 was able to sustain the release of DTX and CIS leading to their slow absorption into the systemic circulation resulting in lower area under the plasma concentration curve at 0–72 h (AUC0–72) and maximum concentration (Cmax) values but longer half-life (T1/2) and mean residence time (MRT) values. An in vivo biodistribution study showed lower DTX and CIS concentrations in organs compared to other treatment groups after IT administration of the dual drug-loaded P13L0.15O1.5. It was concluded that the local co-delivery of DTX and CIS by PLOs may be a promising and effective platform for local anticancer drug delivery with minimal systemic toxicities. © 2018 The Author(s).
原文英語
頁(從 - 到)632-643
頁數12
期刊Drug Delivery
25
發行號1
DOIs
出版狀態已發佈 - 一月 1 2018

Keywords

  • Cisplatin
  • Combination therapy
  • Docetaxel
  • Ovarian cancer
  • Pluronic lecithin organogel

ASJC Scopus subject areas

  • Pharmaceutical Science

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