Abstract
The current assay aimed to fabricate and analyze a potent wound healing structure based on a naringin (Nar)/β-cyclodextrin (β-CD)-loaded chitosan hydrogel. Using the simulation studies, we assessed the interactions among the Nar, β-CD, and the formation of the inclusion complex. Then, the formation of the hydrogel nanocomplex was simulated and evaluated using the in silico methods. The results showed that after optimization of the structures by DMol3 based on DFT-D, the total energies of Nar, GP, CD, and β-CD were calculated at -2100.159, -912.192, -3778.370, and -4273.078 Ha, respectively. The encapsulation energy of Nar on β-CD in the solvent phase was calculated at -93.626 kcal/mol, and the Nar structure was located inside β-CD in solution. The negative interaction energy value for the encapsulation of Nar on β-CD suggests the exothermic adsorption process and a stable structure between Nar and β-CD. Monte Carlo method was applied to obtain adsorption of CS/GP on Nar/β-CD. Its value of the obtained interaction energy was calculated at -1.423 × 103 kcal/mol. The characterization confirmed the formation of a Nar/β-CD inclusion complex. The Zeta potential of the pristine β-CD changed from -4.60 ± 1.1 to -17.60 ± 2.34 mV after interaction with Nar, and the heightened surface negativity can be attributed to the existence of electron-rich naringin molecules, as well as the orientation of the hydroxyl (OH) group of the β-CD toward the surface in an aqueous solution. The porosity of the fabricated hydrogels was in the range of 70-90% and during 14 days around 47.0 ± 3.1% of the pure hydrogel and around 56.4 ± 5.1 of hydrogel nanocomposite was degraded. The MTT assay showed that the hydrogels were biocompatible, and the wound contraction measurement (in an animal model) showed that the closure of the induced wound in the hydrogel nanocomposite treatment was faster than that of the control group (wound without treatment). The results of this study indicate that the developed bioactive wound healing 3D structure, which is composed of a chitosan hydrogel containing a Nar/β-CD inclusion nanocomplex, has potential as an effective material for wound dressing applications.