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

ABSTRACT: 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, P₁₃L_0.15O_1.5, composed of PF127:lecithin:C90 at a 13:0.15:1.5 weight ratio was obtained. The sol-gel transition temperature of P₁₃L_0.15O_1.5 was found to be 33?°C. Tumor inhibition studies illustrated that DTX/CIS-loaded P₁₃L_0.15O_1.5 could efficiently suppress tumor growth by both intratumoral and peritumoral injections in SKOV-3 xenograft mouse model. Pharmacokinetic studies showed that subcutaneous administration of P₁₃L_0.15O_1.5 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 (AUC_0-72) and maximum concentration (C_max) values but longer half-life (T_1/2) 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 P₁₃L_0.15O_1.5. 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.

SUBMITTER: Chang CE

PROVIDER: S-EPMC6058476 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Chang Chia-En CE Hsieh Chien-Ming CM Chen Ling-Chun LC Su Chia-Yu CY Liu Der-Zen DZ Jhan Hua-Jing HJ Ho Hsiu-O HO Sheu Ming-Thau MT

Drug delivery 20181101 1

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 de ...[more]

PMID: 29463123

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Project description:Cachexia is a lethal muscle-wasting syndrome associated with cancer and chemotherapy use. Mounting evidence suggests a correlation between cachexia and intestinal microbiota, but there is presently no effective treatment for cachexia. Whether the Ganoderma lucidum polysaccharide Liz-H exerts protective effects on cachexia and gut microbiota dysbiosis induced by the combination cisplatin plus docetaxel (cisplatin + docetaxel) was investigated. C57BL/6J mice were intraperitoneally injected with cisplatin + docetaxel, with or without oral administration of Liz-H. Body weight, food consumption, complete blood count, blood biochemistry, and muscle atrophy were measured. Next-generation sequencing was also performed to investigate changes to gut microbial ecology. Liz-H administration alleviated the cisplatin + docetaxel-induced weight loss, muscle atrophy, and neutropenia. Furthermore, upregulation of muscle protein degradation-related genes (MuRF-1 and Atrogin-1) and decline of myogenic factors (MyoD and myogenin) after treatment of cisplatin and docetaxel were prevented by Liz-H. Cisplatin and docetaxel treatment resulted in reducing comparative abundances of Ruminococcaceae and Bacteroides, but Liz-H treatment restored these to normal levels. This study indicates that Liz-H is a good chemoprotective reagent for cisplatin + docetaxel-induced cachexia. IMPORTANCE Cachexia is a multifactorial syndrome driven by metabolic dysregulation, anorexia, systemic inflammation, and insulin resistance. Approximately 80% of patients with advanced cancer have cachexia, and cachexia is the cause of death in 30% of cancer patients. Nutritional supplementation has not been shown to reverse cachexia progression. Thus, developing strategies to prevent and/or reverse cachexia is urgent. Polysaccharide is a major biologically active compound in the fungus Ganoderma lucidum. This study is the first to report that G. lucidum polysaccharides could alleviate chemotherapy-induced cachexia via reducing expression of genes that are known to drive muscle wasting, such as MuRF-1 and Atrogin-1. These results suggest that Liz-H is an effective treatment for cisplatin + docetaxel-induced cachexia.

Dataset Information

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

Publications

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

Similar Datasets

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