Synthesis of a PVA-GO drug delivery system for sustained release of 4-methyl umbelliferon

Drug Dev Ind Pharm. 2024 Dec;50(12):1021-1030. doi: 10.1080/03639045.2024.2436530. Epub 2024 Dec 4.

Abstract

Introduction: 4-methyl umbelliferon (4MU) is a coumarin with anti-inflammatory, anti-thrombotic, enzyme-inhibiting, and antioxidant properties. Despite the benefits of the compound, it is eliminated very quickly from the blood circulation through the liver, kidney, and digestive system due to its hydrophobic properties. In this study we proposed to improve the durability of 4MU by binding of 4MU to poly vinyl alcohol (PVA) and graphene oxide (GO).

Methods: The PVA-4MU-GO complex was synthesized and characterized. Release of 4MU from the complex was investigated. H9C2 cells viability was investigated and the entry of complex to the cell was analyzed using flow cytometry.

Result: UV-Vis and FTIR studies confirmed the interaction of 4MU with PVA and GO. SEM measurement also revealed a particle size around 101 nm for PVA-4MU-GO complexes. The obtained results confirmed the assembly of PVA-4MU-GO. A continuous drug release for 8 d (160 h) was achieved. Cytotoxic studies on H9C2 cell showed that PVA-4MU-GO complex is dependent to the concentration of GO and also the relation of 4MU to GO. Sustained release and penetration of PVA-4MU-GO complex into the H9C2 cell were observed.

Conclusion: PVA-4MU-GO complex is recommended as an alternative for 4MU. Synthesis the complex of PVA-4MU-GO, verifying the correct binding, showing the in vitro release of the 4MU, as well as checking its toxicity and its gradual entry into the H9C2 cell, were performed in this study.

Keywords: 4-methyl umbelliferon; H9C2; controlled release; graphene oxide; polyvinyl alcohol.

MeSH terms

  • 4-Hydroxycoumarins / administration & dosage
  • 4-Hydroxycoumarins / chemical synthesis
  • 4-Hydroxycoumarins / chemistry
  • 4-Hydroxycoumarins / pharmacokinetics
  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Delayed-Action Preparations*
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry
  • Drug Delivery Systems* / methods
  • Drug Liberation
  • Graphite* / chemistry
  • Particle Size
  • Polyvinyl Alcohol* / chemistry
  • Rats
  • Umbelliferones / chemical synthesis
  • Umbelliferones / chemistry

Substances

  • Polyvinyl Alcohol
  • Delayed-Action Preparations
  • Graphite
  • graphene oxide
  • Umbelliferones
  • 4-Hydroxycoumarins
  • Drug Carriers