Intraperitoneal Delivery of Cisplatin via a Hyaluronan-Based Nanogel/in Situ Cross-Linkable Hydrogel Hybrid System for Peritoneal Dissemination of Gastric Cancer,Molecular Pharmaceutics

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Intraperitoneal Delivery of Cisplatin via a Hyaluronan-Based Nanogel/in Situ Cross-Linkable Hydrogel Hybrid System for Peritoneal Dissemination of Gastric Cancer
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-08-24 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00349
Seiichi Ohta ₁ , Shota Hiramoto ₂ , Yuki Amano ₃ , Shigenobu Emoto ₄ , Hironori Yamaguchi ₅ , Hironori Ishigami ₄ , Joji Kitayama ₅ , Taichi Ito _{1,

2,

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Affiliation

Intraperitoneal administration of chemotherapeutics is expected for the treatment of peritoneally disseminated gastric cancer because of poor migration of the drugs from the systemic circulation to the peritoneal cavity. In this study, for intraperitoneal delivery of cisplatin (CDDP), we developed a hyaluronan (HA)-based hybrid system in which CDDP-loaded HA nanogels were either physically encapsulated in or chemically conjugated to injectable HA hydrogels. Physical encapsulation enabled sustained release of HA nanogels from the HA hydrogel matrix for over a week. This was a longer release period than that of encapsulated free CDDP, which released 80% of the drug in 2 days. The longer release was attributed to delayed diffusion of HA nanogels from the hydrogel matrix network. The release profile could be tuned by modifying the chemical conjugation of HA nanogels to the HA hydrogel matrix, as well as the type of chelating ligands used to load CDDP to the nanogel. Furthermore, intraperitoneally administered hybrid had significant antitumor activity in a mouse model of peritoneally disseminated gastric cancer, especially for nodules smaller than 1.0 mm.

中文翻译：

通过基于透明质酸的纳米凝胶/原位可交联水凝胶混合系统腹膜内递送顺铂用于胃癌的腹膜扩散。

由于药物从全身循环到腹膜腔的不良迁移，预期腹膜内施用化学疗法可治疗腹膜弥散性胃癌。在这项研究中，对于腹膜内顺铂（CDDP）的递送，我们开发了一种基于透明质酸（HA）的混合系统，其中将CDDP负载的HA纳米凝胶物理包裹或化学偶联到可注射的HA水凝胶中。物理包封能够使HA纳米凝胶从HA水凝胶基质中持续释放超过一周。这比封装的游离CDDP释放时间更长，后者在2天内释放了80％的药物。更长的释放归因于HA纳米凝胶从水凝胶基质网络中的扩散延迟。释放曲线可以通过改变HA纳米凝胶与HA水凝胶基质的化学结合以及用于将CDDP加载到纳米凝胶上的螯合配体的类型进行调整。此外，腹膜内施用的杂种在腹膜弥散性胃癌的小鼠模型中具有显着的抗肿瘤活性，特别是对于小于1.0 mm的结节。

更新日期：2017-08-25

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