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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

Nose–sinus airway model.Notes: (A) There are three anatomical barriers in the nasal airway preventing effective sinus delivery: 1) the nasal valve, 2) the slit opening to the middle meatus, and 3) the ostium to the maxillary sinus. (B) Lateral and front view of the left nasal passage with the ostium and maxillary sinus. A body-fitted mesh is implemented in the near-wall region.
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f1-ijn-10-4847: Nose–sinus airway model.Notes: (A) There are three anatomical barriers in the nasal airway preventing effective sinus delivery: 1) the nasal valve, 2) the slit opening to the middle meatus, and 3) the ostium to the maxillary sinus. (B) Lateral and front view of the left nasal passage with the ostium and maxillary sinus. A body-fitted mesh is implemented in the near-wall region.

Mentions: Among all the complexities of the nose anatomy, there are three challenges that are considered to preclude effective delivery of drugs to the maxillary sinus: the nasal valve, the slit-like opening to the MM, and the narrow ostium to the sinus. The nasal valve has the minimum cross-section area in the nasal chamber and behaves as the flow-limiting sector of the nose. The vena-contracta effects associated with the nasal valve induce elevated particle deposition in the nasal valve area due to the enhanced particle inertial impaction. Previous clinical studies showed that a majority of administered medications with metered-dose inhalers and nasal sprays were wasted in the nasal vestibule and valve regions.1 The second challenge is the slit-opening to the MM, which is formed by two overlapping flaps of turbinate tissues (middle and inferior conchae) and prevents effective air ventilation and particle transport to the MM. During natural breathing, the majority of the air passes through the nasal median passage and only a small fraction of air is ventilated into the MM via the slit opening. The third challenge is the thin ostium to the sinus. Mucus and air from the maxillary sinuses drain into the nose under the middle turbinate through the ostium, which is located high on the nasal lateral wall and opens to the hiatus semilunaris of the MM. The maxillary sinus ostium is a funnel-shaped passage about 3−6 mm in diameter and 1–22 mm in length.13 The area under the middle turbinate is the ostiomeatal complex (OMC), as shown in Figure 1A. Mucus blockage and bacteria proliferation in the OMC are frequent causes of infection in the maxillary sinus. Furthermore, the OMC itself is the most common area for sinusitis disorders and is the primary target for aerosolized drug therapy.13


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)

Nose–sinus airway model.Notes: (A) There are three anatomical barriers in the nasal airway preventing effective sinus delivery: 1) the nasal valve, 2) the slit opening to the middle meatus, and 3) the ostium to the maxillary sinus. (B) Lateral and front view of the left nasal passage with the ostium and maxillary sinus. A body-fitted mesh is implemented in the near-wall region.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-10-4847: Nose–sinus airway model.Notes: (A) There are three anatomical barriers in the nasal airway preventing effective sinus delivery: 1) the nasal valve, 2) the slit opening to the middle meatus, and 3) the ostium to the maxillary sinus. (B) Lateral and front view of the left nasal passage with the ostium and maxillary sinus. A body-fitted mesh is implemented in the near-wall region.
Mentions: Among all the complexities of the nose anatomy, there are three challenges that are considered to preclude effective delivery of drugs to the maxillary sinus: the nasal valve, the slit-like opening to the MM, and the narrow ostium to the sinus. The nasal valve has the minimum cross-section area in the nasal chamber and behaves as the flow-limiting sector of the nose. The vena-contracta effects associated with the nasal valve induce elevated particle deposition in the nasal valve area due to the enhanced particle inertial impaction. Previous clinical studies showed that a majority of administered medications with metered-dose inhalers and nasal sprays were wasted in the nasal vestibule and valve regions.1 The second challenge is the slit-opening to the MM, which is formed by two overlapping flaps of turbinate tissues (middle and inferior conchae) and prevents effective air ventilation and particle transport to the MM. During natural breathing, the majority of the air passes through the nasal median passage and only a small fraction of air is ventilated into the MM via the slit opening. The third challenge is the thin ostium to the sinus. Mucus and air from the maxillary sinuses drain into the nose under the middle turbinate through the ostium, which is located high on the nasal lateral wall and opens to the hiatus semilunaris of the MM. The maxillary sinus ostium is a funnel-shaped passage about 3−6 mm in diameter and 1–22 mm in length.13 The area under the middle turbinate is the ostiomeatal complex (OMC), as shown in Figure 1A. Mucus blockage and bacteria proliferation in the OMC are frequent causes of infection in the maxillary sinus. Furthermore, the OMC itself is the most common area for sinusitis disorders and is the primary target for aerosolized drug therapy.13

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