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Controlled release of indomethacin from alginate-poloxamer-silicon carbide composites decrease in-vitro inflammation.

P Díaz-Rodríguez1, M Landin1

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Summary

Biomorphic silicon carbide (bioSiC) and hydrogel composites effectively load and release drugs for bone therapies. Oak and sapelli bioSiCs show superior anti-inflammatory effects and promote collagen formation in osteoarthritis models.

Keywords:
Anti-inflammatory effectComposite systemControlled releaseOsteochondral defectsWear debris

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Area of Science:

  • Biomaterials Science
  • Materials Engineering
  • Drug Delivery Systems

Background:

  • Developing effective drug delivery systems for poorly soluble drugs is crucial for treating bone pathologies.
  • Biomorphic silicon carbides (bioSiCs) offer a promising ceramic scaffold for drug incorporation.
  • Hydrogels provide a versatile matrix for controlled drug release.

Purpose of the Study:

  • To create and evaluate bioSiC-hydrogel composites for loading and releasing indomethacin, a poorly soluble drug.
  • To investigate the influence of bioSiC microstructure on drug release profiles and therapeutic efficacy.
  • To assess the anti-inflammatory and chondrogenic potential of the developed composites in bone pathology models.

Main Methods:

  • Composites were fabricated using alginate and poloxamer hydrogels loaded with indomethacin, incorporated into selected bioSiCs (oak, sapelli, pine), and crosslinked.
  • Indomethacin release kinetics were analyzed.
  • In vitro studies assessed the modulation of pro-inflammatory cytokine secretion in LPS-stimulated macrophages.
  • Effects on chondrocyte extracellular matrix degradation and collagen formation in osteoarthritic chondrocytes were evaluated.
  • Cytotoxicity of bioSiC particles was assessed.

Main Results:

  • Indomethacin release profiles were significantly influenced by the bioSiC microstructure.
  • Oak and sapelli bioSiC composites demonstrated enhanced anti-inflammatory effects compared to pine bioSiC composites by reducing pro-inflammatory cytokine secretion.
  • Released indomethacin modulated extracellular matrix degradation and promoted new collagen formation in osteoarthritic chondrocytes.
  • Biomorphic silicon carbide particles exhibited low toxicity, comparable to zirconia.

Conclusions:

  • Biomorphic silicon carbide-hydrogel composites are effective for loading and controlled release of poorly soluble drugs like indomethacin for bone pathology therapy.
  • The choice of bioSiC microstructure dictates drug release and therapeutic outcomes, with oak and sapelli showing superior anti-inflammatory and regenerative potential.
  • These composites hold promise for treating inflammatory bone conditions and osteoarthritis by modulating cellular responses and promoting tissue repair.