title: Molecular dynamics of paclitaxel encapsulated by salicylic acid-grafted chitosan oligosaccharide aggregates.
abstract: Chitosan oligosaccharide (COS) derivatives have attracted significant interest in drug delivery systems because of their well-known low toxicity, excellent biocompatibility, and biodegradability. Paclitaxel-loaded nanoparticles based on salicylic acid-grafted chitosan oligosaccharide (COS/SA) were synthesized and characterized. Then, in order to understand the mechanism of the actions of the paclitaxel (PTX) encapsulated by COS/SA, all-atom molecular dynamics simulations were performed to analyze the aggregation of COS/SA molecules. The van der Waals and hydrophobic interactions are the major driving forces for the drug encapsulation process. Electrostatic and hydrogen-bonding interactions also play helpful roles in the COS/SA aggregation. Analyses of the radial distribution function and solvent accessible surface area indicate that the COS/SA nanoparticles are highly hydrosoluble and that the nanoparticles can significantly enhance the aqueous solubility of a hydrophobic drug. Different drug loading systems are also investigated in this work, and the best theoretical drug loading is found to be 10% (w/w). The present work provides insights into the mechanism of the atomic structures of drug-loaded polymeric nanoparticles and presents new perspective for the design of drug delivery systems with desirable properties.
authors.affiliation: Soft Matter Research Center and Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wei
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D001672:Biocompatible Materials; D048271:Chitosan / Q000737:chemistry*; D006860:Hydrogen Bonding; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009844:Oligosaccharides / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry*; D020156:Salicylic Acid / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D009844:Oligosaccharides; D048271:Chitosan; D020156:Salicylic Acid; D017239:Paclitaxel