title: Selecting optimum protein nano-carriers for natural polyphenols using chemoinformatics tools.
abstract: 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.
  
  
  OBJECTIVE
  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, resveratrol-gelatin 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 48h on MCF-7 breast cancer cell-lines scoring an IC50value of 64.8µg/ml. The utilized chemoinformatics tools comprising the molecular dynamics simulations of the protein nano-particulate 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: AbdelKader A
authors.initials: AA
authors.lastname: Metwally
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Sherweit H
authors.initials: SH
authors.lastname: El-Ahmady
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; Bioinformatics program, Faculty of Computer and Information Sciences, Ain Shams University, Cairo, Egypt; Department of Pharmaceutical Technology, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo, Egypt. Electronic address: r_hathout@yahoo.com.
authors.forename: Rania M
authors.initials: RM
authors.lastname: Hathout
mesh_terms: D000418:Albumins / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D053758:Nanoparticles / Q000737:chemistry*; D059808:Polyphenols / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; D004337:Drug Carriers; D059808:Polyphenols; D013267:Stilbenes; D005780:Gelatin; D003474:Curcumin; D000077185:Resveratrol
keywords: Albumin; Curcumin; Docking; Gelatin nanoparticles; Molecular dynamics; Resveratrol