Green synthesis of PEG-coated MIL-100(Fe) for controlled release of dacarbazine and its anticancer potential against human melanoma cells

Int J Pharm. 2022 Apr 25:618:121647. doi: 10.1016/j.ijpharm.2022.121647. Epub 2022 Mar 11.

Abstract

In this study, the potential of using MIL-100(Fe) metal-organic framework (MOF) for loading and controlling the release of dacarbazine (DTIC) was evaluated for in vitro treatment of melanoma. The drug loading was performed during the green synthesis of MIL-100(Fe) in an aqueous media without using any harmful solvents, to obtain MIL-DTIC. The surface of this structure was then coated with polyethylene glycol (PEG) in the same aqueous solution to synthesize MIL-DTIC-PEG. The synthesized samples were characterized using various methods. Their release profile was studied in phosphate-buffered saline (PBS) and simulated cutaneous medium (SCM). The cytotoxicity of DTIC and its nano-MOF formulation were investigated against melanoma A375 cell lines. The results revealed that the PEG coating (PEGylation) changed the surface charge of MOF from -2.8 ± 0.9 mV to -42.8 ± 1.2 mV, which can contribute to the colloidal stability of MOF. The PEGylation showed a significant effect on controlled drug release, especially in SCM, which increases the complete release time from 60 h to 12 days. Moreover, both of the drug-containing MOFs showed more toxicity than DTIC and unloaded MOFs, confirming that the cumulative release of drug and better cellular uptake of NPs lead to increased toxicity.

Keywords: Dacarbazine; Drug delivery; MIL-100(Fe); Melanoma; Metal-organic framework.

MeSH terms

  • Dacarbazine / pharmacology
  • Delayed-Action Preparations / therapeutic use
  • Humans
  • Melanoma* / drug therapy
  • Metal-Organic Frameworks* / chemistry
  • Polyethylene Glycols / therapeutic use

Substances

  • Dacarbazine
  • Delayed-Action Preparations
  • Metal-Organic Frameworks
  • Polyethylene Glycols