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

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.

Keywords: cancer; gel-PEG-Cys; gold porphyrin; in situ interpenetrating network system (IPN).

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Biocompatible Materials / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gelatin / chemistry
  • Gold Compounds / pharmacology*
  • Heterografts / drug effects*
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Hydrogels / pharmacology*
  • Kinetics
  • Lung Neoplasms / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neovascularization, Pathologic / drug therapy
  • Polyethylene Glycols / chemistry
  • Transplantation, Heterologous / methods

Substances

  • Antineoplastic Agents
  • Biocompatible Materials
  • Gold Compounds
  • Hydrogels
  • poly(ethylene glycol)diacrylate
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Polyethylene Glycols
  • Gelatin