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

Drug Delivery

Der-Zen Liu¹  Hsiu-O Ho²  Hua-Jing Jhan²  Chien-Ming Hsieh²  Chia-En Chang²  Chia-Yu Su²  Ming-Thau Sheu³  Ling-Chun Chen⁴ 

[1] Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan, ROC;School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC;School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC;Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan, RO;School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC;Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan, ROC;

关键词: Docetaxel;    cisplatin;    combination therapy;    pluronic lecithin organogel;    ovarian cancer;   

DOI  :  10.1080/10717544.2018.1440444

来源: publisher

【 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.

【 授权许可】

CC BY