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多功能水凝胶递运金化合物并抑制人肺癌异种移植。

A Multifunctional Hydrogel Delivers Gold Compound and Inhibits Human Lung Cancer Xenograft.

机构信息

Department of Chemistry and Chemical Biology Centre, The University of Hong Kong, Pokfulam, Hong Kong.

Department of Biomedical Engineering, The University of Hong Kong, Pokfulam, Hong Kong.

出版信息

Pharm Res. 2019 Mar 8;36(4):61. doi: 10.1007/s11095-019-2581-z.

Abstract

PURPOSE

Interpenetrating network system (IPN), consisting of polyethylene glycol (PEG) -diacrylate (PEGdA) and modified gelatin, is a biocompatible and biodegradable hydrogel and has been studied for the local delivery of bioactive molecules and drugs. Gold(III) porphyrin(AuP) is a stable metal compound in the development for anticancer application when administered systemically. The aim of this work is to develop a novel formulation for AuP based on IPN for local delivery.

METHODS

IPN loaded with AuP hydrogel was optimized and synthesized. Drug release kinetics, cytotoxicity against tumor cells, and antitumor activity in lung cancer bearing nude mice were studied.

RESULTS

AuP released from the IPN followed a first order kinetics in vitro. The AuP loaded IPN showed higher cytotoxicity against human lung cancer cell lines compared to IPN only. In mice bearing human lung cancer xenograft, AuP loaded IPN inhibited tumor growth and reduced angiogenesis. No sign of systemic toxicity was observed for all treatment groups.

CONCLUSION

AuP loaded IPN provides an improved formulation over systemic delivery for tumor inhibition to complement surgical intervention. Graphical Abstract Injectable multifunctional matrix of polyethylene glycol and gelatin derivatives for the delivery of gold porphyrinto inhibit tumor growth.

摘要

目的

由聚乙二醇二丙烯酸酯(PEGdA)和改性明胶组成的互穿网络系统(IPN)是一种生物相容性和可生物降解的水凝胶,已被研究用于局部递送生物活性分子和药物。金(III)卟啉(AuP)是一种稳定的金属化合物,当全身给药时,可用于癌症治疗。本研究旨在开发一种基于 IPN 的新型 AuP 制剂,用于局部递送。

方法

优化并合成了载有 AuP 的 IPN。研究了药物释放动力学、对肿瘤细胞的细胞毒性以及荷肺癌裸鼠的抗肿瘤活性。

结果

AuP 从 IPN 中的释放遵循体外一级动力学。与仅 IPN 相比,负载 AuP 的 IPN 对人肺癌细胞系表现出更高的细胞毒性。在荷有人肺癌异种移植的小鼠中,载 AuP 的 IPN 抑制肿瘤生长并减少血管生成。所有治疗组均未观察到全身毒性迹象。

结论

载 AuP 的 IPN 为肿瘤抑制提供了一种优于全身递送的改良制剂,可与手术干预相结合。示意图 用于递送金卟啉以抑制肿瘤生长的聚乙二醇和明胶衍生物的可注射多功能基质。

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