FF‐10832 enables long survival via effective gemcitabine accumulation in a lethal murine peritoneal dissemination model

Higuchi, Taiichi; Yokobori, Takehiko; Takahashi, Ryo; Naito, Tomoharu; Kitahara, Hiromu; Matsumoto, Takeshi; Kakinuma, Chihaya; Hagiwara, Shinji; Kuwano, Hiroyuki; Shirabe, Ken; Asao, Takayuki

doi:10.1111/cas.14123

Cited by 3 publications

(2 citation statements)

References 25 publications

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“…Preparation of Lipid Encapsulated FF-10832 and Labeled FF-10832 FF-10832 was prepared as previously reported (20). Briefly, an empty liposome containing cholesterol, HSPC, and N-MPEG-DSPE at a molar ratio of 4:15:1 was first prepared.…”

Section: Methodsmentioning

confidence: 99%

“…Although we have reported plasma and tumor concentrations of GEM in a mouse model of Colon26 peritoneal dissemination after FF-10832 administration (20), the detailed pharmacokinetics of FF-10832 in mice with human pancreatic tumors are still unclear. The plasma and tumor concentration profiles of GEM were measured in mice with Capan-1 tumors after administration of FF-10832 at a dose of 4 mg/kg, and compared with those in mice after administration of GEM at a dose of 240 mg/kg.…”

Section: Pharmacokinetics Of Ff-10832 In Mice With Capan-1 Tumorsmentioning

confidence: 98%

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A Liposomal Gemcitabine, FF-10832, Improves Plasma Stability, Tumor Targeting, and Antitumor Efficacy of Gemcitabine in Pancreatic Cancer Xenograft Models

et al. 2021

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Purpose The clinical application of gemcitabine (GEM) is limited by its pharmacokinetic properties. The aim of this study was to characterize the stability in circulating plasma, tumor targeting, and payload release of liposome-encapsulated GEM, FF-10832. Methods Antitumor activity was assessed in xenograft mouse models of human pancreatic cancer. The pharmacokinetics of GEM and its active metabolite dFdCTP were also evaluated. Results In mice with Capan-1 tumors, the dose-normalized areas under the curve (AUCs) after FF-10832 administration in plasma and tumor were 672 and 1047 times higher, respectively, than after using unencapsulated GEM. The tumor-to-bone marrow AUC ratio of dFdCTP was approximately eight times higher after FF-10832 administration than after GEM administration. These results indicated that liposomal encapsulation produced long-term stability in circulating plasma and tumor-selective targeting of GEM. In mice with Capan-1, SUIT-2, and BxPC-3 tumors, FF-10832 had better antitumor activity and tolerability than GEM. Internalization of FF-10832 in tumor-associated macrophages (TAMs) was revealed by flow cytometry and confocal laser scanning microscopy, and GEM was efficiently released from isolated macrophages of mice treated with FF-10832. These results suggest that TAMs are one of the potential reservoirs of GEM in tumors. Conclusion This study found that FF-10832 had favorable pharmacokinetic properties. The liposomal formulation was more effective and tolerable than unencapsulated GEM in mouse xenograft tumor models. Hence, FF-10832 is a promising candidate for the treatment of pancreatic cancer.

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Section: Methodsmentioning

confidence: 99%

Section: Pharmacokinetics Of Ff-10832 In Mice With Capan-1 Tumorsmentioning

confidence: 98%

A Liposomal Gemcitabine, FF-10832, Improves Plasma Stability, Tumor Targeting, and Antitumor Efficacy of Gemcitabine in Pancreatic Cancer Xenograft Models

et al. 2021

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The Use of Phospholipids to Make Pharmaceutical Form Line Extensions

Hoogevest

Tiemessen

Metselaar

et al. 2021

Euro J Lipid Sci & Tech

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This review describes the use of phospholipid excipients to make Pharmaceutical Form (Dosage Form) Line Extensions of existing drugs as part of a Product Life Cycle Management. Product examples and development candidates, which show the versatility of phospholipids as key excipients in formulations to develop line extension drug products for any administration route by reformulating existing products, are provided. The resulting patented products enable the application of a drug substance for another administration route or show an increased efficacy and/or reduced toxicity of the formulated drug substances, or enable a more convenient use, through reduction of dosing frequency, or adapt a product for regulatory requirements for specific patient populations. Parenteral line extensions for lipophilic drugs using non‐toxic phospholipid‐based solubilising formulations are clearly an alternative to products with solubilising synthetic detergents with the risk for allergic and anaphylactic reactions. This review draws the attention to academic and industrial formulation scientist to consider using phospholipid excipients to reformulate existing products to improve the product properties by an active product life cycle management. Phospholipids are suitable for this purpose because they are biocompatible, biodegradable, non‐toxic, and available at large scale and of pharmaceutical grade. Besides, they are well known to regulatory authorities.

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Perspectives de vectorisation de thérapie photodynamique par des vésicules extra-membranaires, dans le traitement de métastases péritonéales d'origine colique

Pinto.¹,

Marangon²,

Méreaux³

et al. 2021

Bulletin de l'Académie Nationale de Médecine

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FF‐10832 enables long survival via effective gemcitabine accumulation in a lethal murine peritoneal dissemination model

Cited by 3 publications

References 25 publications

A Liposomal Gemcitabine, FF-10832, Improves Plasma Stability, Tumor Targeting, and Antitumor Efficacy of Gemcitabine in Pancreatic Cancer Xenograft Models

A Liposomal Gemcitabine, FF-10832, Improves Plasma Stability, Tumor Targeting, and Antitumor Efficacy of Gemcitabine in Pancreatic Cancer Xenograft Models

The Use of Phospholipids to Make Pharmaceutical Form Line Extensions

Perspectives de vectorisation de thérapie photodynamique par des vésicules extra-membranaires, dans le traitement de métastases péritonéales d'origine colique

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