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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

Optimization of the release position (x, z) at the nostril inlet.Notes: (A) The objective (ie, OMC dose) as a function of the release position, (B) the Nelder-Mead optimization sequence with triangles (Tk) converging to the point (10.2, 6.1 [mm]), (C) particle deposition pattern with the optimized inlet position, and (D) the time evolution of olfactory deposition for OMC deposition with and without inlet-position optimization.Abbreviations: OMC, ostiomeatal complex; s, seconds.
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f7-ijn-10-4847: Optimization of the release position (x, z) at the nostril inlet.Notes: (A) The objective (ie, OMC dose) as a function of the release position, (B) the Nelder-Mead optimization sequence with triangles (Tk) converging to the point (10.2, 6.1 [mm]), (C) particle deposition pattern with the optimized inlet position, and (D) the time evolution of olfactory deposition for OMC deposition with and without inlet-position optimization.Abbreviations: OMC, ostiomeatal complex; s, seconds.

Mentions: In order to find the best efficiency, all design components listed in Figure 6 were optimized except the particle density. Optimization of the center of the drug-release nozzle (x, z) is shown in Figure 7. The nozzle is positioned at the nostril and has a rectangular shape and a fixed area of 5.25 mm2 (Figure 3). Figure 7A displays the 3-D plot of the objective functions versus the release position. The Nelder-Mead algorithm explored different points in the design space, which gave different OMC doses and identified the optimal point after 24 steps. The optimization process is also illustrated in Figure 7B with multiple triangles (or simplexes), which progressively shrink in size and converge to the optimal point. At each step, the objective functions of the three points were compared, and the worst was replaced with a new point that was determined by the Nelder-Mead algorithm (Figure 7B). The optimization process stopped when the difference among the objectives is <1e-5.


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)

Optimization of the release position (x, z) at the nostril inlet.Notes: (A) The objective (ie, OMC dose) as a function of the release position, (B) the Nelder-Mead optimization sequence with triangles (Tk) converging to the point (10.2, 6.1 [mm]), (C) particle deposition pattern with the optimized inlet position, and (D) the time evolution of olfactory deposition for OMC deposition with and without inlet-position optimization.Abbreviations: OMC, ostiomeatal complex; s, seconds.
© Copyright Policy
Related In: Results  -  Collection

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

f7-ijn-10-4847: Optimization of the release position (x, z) at the nostril inlet.Notes: (A) The objective (ie, OMC dose) as a function of the release position, (B) the Nelder-Mead optimization sequence with triangles (Tk) converging to the point (10.2, 6.1 [mm]), (C) particle deposition pattern with the optimized inlet position, and (D) the time evolution of olfactory deposition for OMC deposition with and without inlet-position optimization.Abbreviations: OMC, ostiomeatal complex; s, seconds.
Mentions: In order to find the best efficiency, all design components listed in Figure 6 were optimized except the particle density. Optimization of the center of the drug-release nozzle (x, z) is shown in Figure 7. The nozzle is positioned at the nostril and has a rectangular shape and a fixed area of 5.25 mm2 (Figure 3). Figure 7A displays the 3-D plot of the objective functions versus the release position. The Nelder-Mead algorithm explored different points in the design space, which gave different OMC doses and identified the optimal point after 24 steps. The optimization process is also illustrated in Figure 7B with multiple triangles (or simplexes), which progressively shrink in size and converge to the optimal point. At each step, the objective functions of the three points were compared, and the worst was replaced with a new point that was determined by the Nelder-Mead algorithm (Figure 7B). The optimization process stopped when the difference among the objectives is <1e-5.

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