Curcumin encapsulated polylactic acid nanoparticles embedded in alginate/gelatin bioinks for in situ immunoregulation: Characterization and biological assessment

Int J Biol Macromol. 2022 Nov 30:221:1218-1227. doi: 10.1016/j.ijbiomac.2022.09.014. Epub 2022 Sep 7.

Abstract

Curcumin is a known naturally occurring anti-inflammatory agent derived from turmeric, and it is commonly used as a herbal food supplement. Here, in order to overcome the inherent hydrophobicity of curcumin (Cur), polylactic acid (PLA) nanoparticles (NPs) were synthesised using a solvent evaporation, and an oil-in-water emulsion method used to encapsulate curcumin. Polymeric NPs also offer the ability to control rate of drug release. The newly synthesised NPs were analysed using a scanning electron microscope (SEM), where results show the NPs range from 50 to 250 nm. NPs containing graded amounts of curcumin (0 %, 0.5 %, and 2 %) were added to cultures of NIH3T3 fibroblast cells for cytotoxicity evaluation using the Alamar Blue assay. Then, the curcumin NPs were incorporated into an alginate/gelatin solution, prior to crosslinking using a calcium chloride solution (200 nM). These hydrogels were then characterised with respect to their chemical, mechanical and rheological properties. Following hydrogel optimization, hydrogels loaded with NP containing 2 % curcumin were selected as a candidate as a bioink for three-dimensional (3D) printing. The biological assessment for these bioinks/hydrogels were conducted using THP-1 cells, a human monocytic cell line. Cell viability and immunomodulation were evaluated using lactate dehydrogenase (LHD) and a tumour necrosis factor alpha (TNF-α) enzyme-linked immunosorbent (ELISA) assay, respectively. Results show that the hydrogels were cytocompatible and supressed the production of TNF-α. These bioactive hydrogels are printable, supress immune cell activation and inflammation showing immense potential for the fabrication of tissue engineering constructs.

Keywords: Alginate; Bioink; Curcumin; Hydrogel; Immunomodulation; Intervertebral disc degeneration; Nanoparticles.

MeSH terms

  • Alginates / chemistry
  • Animals
  • Curcumin* / chemistry
  • Curcumin* / pharmacology
  • Gelatin / chemistry
  • Humans
  • Hydrogels / chemistry
  • Mice
  • NIH 3T3 Cells
  • Nanoparticles* / chemistry
  • Polyesters
  • Printing, Three-Dimensional
  • Tumor Necrosis Factor-alpha

Substances

  • Curcumin
  • Gelatin
  • Alginates
  • poly(lactide)
  • Tumor Necrosis Factor-alpha
  • Polyesters
  • Hydrogels