Nanoparticle-mediated interplay of chitosan and melatonin for improved wound epithelialisation

• The lecithin/chitosan nanoparticles were prepared using four types of chitosan that differed in terms of molecular weight (50–150 or 150–400 kDa) and/or deacetylation degree (75–90 or >90%).
• For all lecithin/chitosan nanoparticles prepared biphasic prolonged melatonin release was obtained.
• The model wounds were treated with nanoparticle suspensions at a chitosan concentration determined in preceding cell biocompatibility studies.
• Nanoparticles prepared with different types of chitosan showed similar effect on the keratinocyte proliferation/migration.
• Nanoparticle-mediated interplay of chitosan and melatonin was shown to be crucial for improved wound epithelialisation.

Herein, we propose an innovative approach to improving wound healing. Our strategy is to deliver melatonin locally at the wound site by means of lecithin/chitosan nanoparticles. We used four types of chitosan that differed in terms of molecular weight and/or deacetylation degree. Melatonin encapsulation efficiency, nanoparticle size, zeta potential, biocompatibility and in vitro drug release were studied as a function of the type of chitosan used in preparation. The nanoparticles were evaluated in terms of their potential to promote wound epithelialisation via an in vitro scratch assay using a human keratinocyte (HaCaT) monolayer. The model wounds were treated with nanoparticle suspensions at a chitosan concentration of 5 μg ml−1, which was based on preceding cell biocompatibility studies. Nanoparticles prepared with different types of chitosan showed similar effect on the keratinocyte proliferation/migration. Nanoparticle-mediated interplay of chitosan and melatonin was shown to be crucial for improved wound epithelialisation.