Puiyan Lee1, Chun-Nam Lok1, Chi-Ming Che2, Weiyuan John Kao3,4,5. 1. Department of Chemistry and Chemical Biology Centre, The University of Hong Kong, Pokfulam, Hong Kong. 2. Department of Chemistry and Chemical Biology Centre, The University of Hong Kong, Pokfulam, Hong Kong. cmche@hku.hk. 3. Department of Chemistry and Chemical Biology Centre, The University of Hong Kong, Pokfulam, Hong Kong. wjkao@hku.hk. 4. Department of Biomedical Engineering, The University of Hong Kong, Pokfulam, Hong Kong. wjkao@hku.hk. 5. Li Ka Shing Faculty of Medicine, Pokfulam, Hong Kong. wjkao@hku.hk.
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.
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 humanlung cancer cell lines compared to IPN only. In mice bearing humanlung 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.
Entities:
Keywords:
cancer; gel-PEG-Cys; gold porphyrin; in situ interpenetrating network system (IPN)
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