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Numerical optimization of targeted delivery of charged nanoparticles to the ostiomeatal complex for treatment of rhinosinusitis.

Xi J, Yuan JE, Si XA, Hasbany J - Int J Nanomedicine (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Engineering and Technology, Central Michigan University, Mount Pleasant, MI, USA.

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.

Results and discussion: 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.

No MeSH data available.


Related in: MedlinePlus

Electrode layout and performance of a baseline design.Notes: (A) Diagram of the electrode layout with three groups and the electric potential field; (B) desirable path of particles for effective OMC delivery, and (C) depositions with the baseline delivery system. Each electrode group in the proposed delivery system has a designated function. E-group 1 aims to reduce drug deposition in the nasal valve, E-group 2 aims to push particles into the middle meatus, and E-group 3 aims to attract particles to the sinus ostium. Point-release was used to minimize drug loss in regions other than the target.Abbreviations: OMC, ostiomeatal complex; T, top; B, bottom; C, cone.
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f5-ijn-10-4847: Electrode layout and performance of a baseline design.Notes: (A) Diagram of the electrode layout with three groups and the electric potential field; (B) desirable path of particles for effective OMC delivery, and (C) depositions with the baseline delivery system. Each electrode group in the proposed delivery system has a designated function. E-group 1 aims to reduce drug deposition in the nasal valve, E-group 2 aims to push particles into the middle meatus, and E-group 3 aims to attract particles to the sinus ostium. Point-release was used to minimize drug loss in regions other than the target.Abbreviations: OMC, ostiomeatal complex; T, top; B, bottom; C, cone.

Mentions: The diagram of the delivery system for charged particles is shown in Figure 1B and will be discussed in detail in Figure 5. The proposed delivery system consists of multiple electrodes positioned around the nose. After a charged particle is released into the nose, an electric force is exerted onto it and makes it depart from its original path. With a proper electric field, the particle can be guided to the target site with reduced deposition in the anterior nose. To further enhance the delivery efficiency, drug particles can be released into the nose from a selected point instead of the entire nostril, that is, point drug release.23,32 In practice, a vibrating mesh nebulizer can be used to generate submicrometer particles, which acquire electrostatic charges through either induction or corona charging.38,39 The charged particles subsequently enter a focusing chamber to form a particle beam, which is accelerated to a particular exit speed.40 The benefit of knowing the particle release velocity is that the particle trajectory can be found, and the path adjustments required for improved depositions can be determined. The target in this study is the OMC, which hosts the ostium orifice to the maxillary sinus and is where most sinusitis disorders occur.41


Numerical optimization of targeted delivery of charged nanoparticles to the ostiomeatal complex for treatment of rhinosinusitis.

Xi J, Yuan JE, Si XA, Hasbany J - Int J Nanomedicine (2015)

Electrode layout and performance of a baseline design.Notes: (A) Diagram of the electrode layout with three groups and the electric potential field; (B) desirable path of particles for effective OMC delivery, and (C) depositions with the baseline delivery system. Each electrode group in the proposed delivery system has a designated function. E-group 1 aims to reduce drug deposition in the nasal valve, E-group 2 aims to push particles into the middle meatus, and E-group 3 aims to attract particles to the sinus ostium. Point-release was used to minimize drug loss in regions other than the target.Abbreviations: OMC, ostiomeatal complex; T, top; B, bottom; C, cone.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525801&req=5

f5-ijn-10-4847: Electrode layout and performance of a baseline design.Notes: (A) Diagram of the electrode layout with three groups and the electric potential field; (B) desirable path of particles for effective OMC delivery, and (C) depositions with the baseline delivery system. Each electrode group in the proposed delivery system has a designated function. E-group 1 aims to reduce drug deposition in the nasal valve, E-group 2 aims to push particles into the middle meatus, and E-group 3 aims to attract particles to the sinus ostium. Point-release was used to minimize drug loss in regions other than the target.Abbreviations: OMC, ostiomeatal complex; T, top; B, bottom; C, cone.
Mentions: The diagram of the delivery system for charged particles is shown in Figure 1B and will be discussed in detail in Figure 5. The proposed delivery system consists of multiple electrodes positioned around the nose. After a charged particle is released into the nose, an electric force is exerted onto it and makes it depart from its original path. With a proper electric field, the particle can be guided to the target site with reduced deposition in the anterior nose. To further enhance the delivery efficiency, drug particles can be released into the nose from a selected point instead of the entire nostril, that is, point drug release.23,32 In practice, a vibrating mesh nebulizer can be used to generate submicrometer particles, which acquire electrostatic charges through either induction or corona charging.38,39 The charged particles subsequently enter a focusing chamber to form a particle beam, which is accelerated to a particular exit speed.40 The benefit of knowing the particle release velocity is that the particle trajectory can be found, and the path adjustments required for improved depositions can be determined. The target in this study is the OMC, which hosts the ostium orifice to the maxillary sinus and is where most sinusitis disorders occur.41

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Engineering and Technology, Central Michigan University, Mount Pleasant, MI, USA.

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.

Results and discussion: 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.

No MeSH data available.


Related in: MedlinePlus