Physicochemical, structural and biological characterisation of poly(3-hydroxyoctanoate) supplemented with diclofenac acid conjugates - Harnessing the potential in the construction of materials for skin regeneration processes

Int J Biol Macromol. 2024 May;268(Pt 1):131476. doi: 10.1016/j.ijbiomac.2024.131476. Epub 2024 Apr 16.

Abstract

This study involved creating oligomeric conjugates of 3-hydroxy fatty acids and diclofenac, named Dic-oligo(3HAs). Advanced NMR techniques confirmed no free diclofenac in the mix. We tested diclofenac release under conditions resembling healthy and chronic wound skin. These oligomers were used to make P(3HO) blends, forming patches for drug delivery. Their preparation used the solvent casting/porogen leaching (SCPL) method. The patches' properties like porosity, roughness, and wettability were thoroughly analysed. Antimicrobial assays showed that Dic-oligo(3HAs) exhibited antimicrobial activity against reference (S. aureus, S. epidermis, S. faecalis) and clinical (Staphylococcus spp.) strains. Human keratinocytes (HaCaT) cell line tests, as per ISO 10993-5, showed no toxicity. A clear link between material roughness and HaCaT cell adhesion was found. Deep cell infiltration was verified using DAPI and phalloidin staining, observed under confocal microscopy. SEM also confirmed HaCaT cell growth on these scaffolds. The strong adhesion and proliferation of HaCaT cells on these materials indicate their potential as wound dressing layers. Additionally, the successful diclofenac release tests point to their applicability in treating both normal and chronic wounds.

Keywords: Artificial skin substitute, bioresorbable, porous layer of dressing material; Poly(3-hydroxyoctanoate); Polyhydroxyalkanoates; Targeted delivery of diclofenac.

MeSH terms

  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Cell Line
  • Cell Proliferation / drug effects
  • Chemical Phenomena
  • Diclofenac* / chemistry
  • Diclofenac* / pharmacology
  • HaCaT Cells
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Polymers / chemistry
  • Porosity
  • Regeneration / drug effects
  • Skin* / drug effects
  • Wound Healing / drug effects