Selecting optimum protein nano-carriers for natural polyphenols using chemoinformatics tools

Background: The normal fate of any natural product with a therapeutic potential is to be formulated into an effective medicine. However, the conventional methods of selecting the suitable formulations or carriers based on the formulator experiences, trials and errors as well as materials availability do not usually yield the optimal results. Hypothesis: We hypothesize the possibility of the virtual optimum selection of a protein carrier for two polyphenolic compounds widely investigated for their chemopreventive effects; resveratrol and curcumin using a combination of some chemoinformatics tools. Methods: Two protein-based nanoparticles namely; albumin and gelatin nanoparticles were compared as carriers for the two selected phytochemicals; resveratrol and curcumin. Resveratrol-albumin, resveratrolgelatin and curcumin-albumin results were gathered from the literature. While, a new combination (formulation), comprising curcumin as the cargo and gelatin nanoparticles as the carrier, was prepared and evaluated as a potential medicine for breast cancer. Combined chemoinformatics tools, namely; molecular dynamics and molecular docking were used to determine the optimum carrier for each of the two chemopreventive agents. Results: A new curcumin-gelatin nanoparticulate formulation was prepared and proven cytotoxic after an application period of 48 h on MCF-7 breast cancer cell-lines scoring an IC50 value of 64.8 mu g/ml. The utilized chemoinformatics tools comprising the molecular dynamics simulations of the protein nanoparticulate drug-carriers followed by the molecular docking of phytochemical drugs on these carriers could capture the optimum protein carrier for each of the tested phytochemical and hence propose a successful formulation. Conclusion: This study presents one in a series that proves the novel addressed concept of the utilization of computational tools rather than wet-lab experimentation in providing better selection of drug-carrier pairs aiming for better formulations and the subsequent successful therapeutic effects. (C) 2016 Elsevier GmbH. All rights reserved.