In Silico Modeling Study of Curcumin Diffusion and Cellular Growth

Abstract

Curcumin can enhance cutaneous wound healing by improving fibroblast proliferation. However, its therapeutic properties are dose-dependent: high concentrations produce cytotoxic effects, whereas low concentrations benefit cell proliferation. Similarly, the type of administration and its moderation are key aspects, as an erroneous distribution may result in null or noxious activity to the organism. In silico models for curcumin diffusion work as predictive tools for evaluating curcumin’s cytotoxic effects and establishing therapeutic windows. A 2D fibroblast culture growth model was created based on a model developed by Gérard and Goldbeter. Similarly, a curcumin diffusion model was developed by adjusting experimental release values obtained from Aguilar-Rabiela et al. and fitted to Korsmeyer–Peppas and Peleg’s hyperbolic models. The release of six key curcumin concentrations was achieved. Both models were integrated using Morpheus software, and a scratch-wound assay simulated curcumin’s dose-dependent effects on wound healing. The most beneficial effect was achieved at 0.25 μM, which exhibited the lowest cell-division period, the highest confluence (~60% for both release models, 447 initial cells), and the highest final cell population. The least beneficial effect was found at 20 μM, which inhibited cell division and achieved the lowest confluence (~34.30% for both release models, 447 initial cells). Confluence was shown to decrease as curcumin concentration increased, since higher concentrations of curcumin have inhibitory and cytotoxic effects.