title: Numerical optimization of targeted delivery of charged nanoparticles to the ostiomeatal complex for treatment of rhinosinusitis.
abstract: BACKGROUND
  Despite the prevalence of rhinosinusitis that affects 10%-15% of the population, current inhalation therapy shows limited efficacy. Standard devices deliver <5% of the drugs to the sinuses due to the complexity of nose structure, secluded location of the sinus, poor ventilation, and lack of control of particle motions inside the nasal cavity.
  
  
  METHODS
  An electric-guided delivery system was developed to guide charged particles to the ostiomeatal complex (OMC). Its performance was numerically assessed in an MRI-based nose-sinus model. Key design variables related to the delivery device, drug particles, and patient breathing were determined using sensitivity analysis. A two-stage optimization of design variables was conducted to obtain the best performance of the delivery system using the Nelder-Mead algorithm.
  
  
  CONCLUSIONS
  The OMC delivery system exhibited high sensitivity to the applied electric field and electrostatic charges carried by the particles. Through the synthesis of electric guidance and point drug release, the new delivery system eliminated particle deposition in the nasal valve and turbinate regions and significantly enhanced the OMC doses. An OMC delivery efficiency of 72.4% was obtained with the optimized design, which is one order of magnitude higher than the standard nasal devices. Moreover, optimization is imperative to achieve a sound delivery protocol because of the large number of design variables. The OMC dose increased from 45.0% in the baseline model to 72.4% in the optimized system. The optimization framework developed in this study can be easily adapted for the delivery of drugs to other sites in the nose such as the ethmoid sinus and olfactory region.
authors.affiliation: School of Engineering and Technology, Central Michigan University, Mount Pleasant, MI, USA.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Xi
authors.affiliation: School of Engineering and Technology, Central Michigan University, Mount Pleasant, MI, USA.
authors.forename: Jiayao Eddie
authors.initials: JE
authors.lastname: Yuan
authors.affiliation: Department of Mechanical Engineering, California Baptist University, Riverside, CA, USA.
authors.forename: Xiuhua April
authors.initials: XA
authors.lastname: Si
authors.affiliation: School of Engineering and Technology, Central Michigan University, Mount Pleasant, MI, USA.
authors.forename: James
authors.initials: J
authors.lastname: Hasbany
mesh_terms: D000281:Administration, Intranasal / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use; D010256:Paranasal Sinuses / Q000502:physiology*; D012220:Rhinitis / Q000188:drug therapy*; D012852:Sinusitis / Q000188:drug therapy*
keywords: charged particles; electric guidance; intranasal aerosol drug delivery; maxillary sinus; ostiomeatal complex; rhinosinusitis