Modeling of release position and ventilation effects on olfactory aerosol drug delivery

Xiuhua, A.; Xi, Jinxiang; Kim, Jong-Won; Zhou, Yue; Zhong, Hualiang

doi:10.1016/j.resp.2012.12.005

Cited by 66 publications

(50 citation statements)

References 57 publications

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“…17,25,26 The regional deposition allocations we observed varied substantially among the different age models. Considering that tissues receiving higher depositions of toxicants are more vulnerable to injury, such results might help to elucidate the diverse etiology and symptoms of respiratory disorders in different subjects or age groups.…”

Section: Discussionmentioning

confidence: 89%

Growth of Nasal and Laryngeal Airways in Children: Implications in Breathing and Inhaled Aerosol Dynamics

Zhou

et al. 2013

Respir Care

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BACKGROUND:The human respiratory airway undergoes dramatic growth during infancy and childhood, which induces substantial variability in air flow pattern and particle deposition. However, deposition studies have typically focused on adult subjects, the results of which cannot be readily extrapolated to children. We developed models to quantify the growth of human nasallaryngeal airways at early ages, and to evaluate the impact of that growth on breathing resistance and aerosol deposition. METHODS: Four image-based nasal-laryngeal models were developed from 4 children, ages 10 days, 7 months, 3 years, and 5 years, and were compared to a nasallaryngeal model of a 53-year-old adult. The airway dimensions were quantified in terms of different parameters (volume, cross-section area, and hydraulic diameter) and of different anatomies (nose, pharynx, and larynx). Breathing resistance and aerosol deposition were computed using a highfidelity fluid-particle transport model, and were validated against the measurements made with the 3-dimensional models fabricated from the same airway computed tomography images. RESULTS: Significant differences in nasal morphology were observed among the 5 subjects, in both morphology and dimension. The turbinate region appeared to experience the most noticeable growth during the first 5 years of life. The nasal airway volume ratios of the 10-day, 7-month, 3-year, and 5-year-old subjects were 6.4%, 18.8%, 24.2%, and 40.3% that of the adult, respectively. Remarkable inter-group variability was observed in air flow, pressure drop, deposition fraction, and particle accumulation. The computational fluid dynamics predicted pressure drops and deposition fractions were in close agreement with in vitro measurements. CONCLUSIONS: Age effects are significant in both breathing resistance and micrometer particle deposition. The image/computational-fluid-dynamics coupled method provides an efficient and effective approach in understanding patient-specific air flows and particle deposition, which have important implications in pediatric inhalation drug delivery and respiratory disorder diagnosis.

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Section: Discussionmentioning

confidence: 89%

Growth of Nasal and Laryngeal Airways in Children: Implications in Breathing and Inhaled Aerosol Dynamics

Zhou

et al. 2013

Respir Care

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“…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.…”

Section: Nose-sinus Model and Electric-guided Delivery Systemmentioning

confidence: 99%

“…32,44 In this study, these positions are identified inversely by tracing all particles that deposit in the sinus back to their original release position ( Figure 3A). The logic is that a particle released from this region (blue-dashed rectangle) has a larger chance to penetrate into the sinus.…”

Section: Point-release Positionmentioning

confidence: 99%

“…As discussed in Si et al a particle released from the nostril tip can go relatively upward to the vicinity of the olfactory region; however, a particle that reaches the maxillary sinus needs to circumvent three obstacles ( Figure 1A) and experiences more dramatic direction changes. 32 This challenge could be worse in patients with rhinosinusitis who have blocked ostium, obstructed …”

Section: Introductionmentioning

confidence: 99%

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

Xi¹,

Yuan²,

April³

et al. 2015

IJN

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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.

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“…1,2 However, its application is limited by the extremely low delivery efficiency (1%) of conventional devices to the olfactory region where drugs can directly enter the brain. 3,4 This poor bioavailability is mainly attributed to two reasons: 1) the complexity of the nasal structure that traps particles before reaching the olfactory region, 5 2) the complete lack of control on particle motions after their release at the nostrils. The structure of a human nose is highly complex, with narrow, convoluted channels ( Figure 1A).…”

Section: Introductionmentioning

confidence: 99%

Improving intranasal delivery of neurological nanomedicine to the olfactory region using magnetophoretic guidance of microsphere carriers

Xi¹,

Zhang²,

Xiuhua³

2015

IJN

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Background Although direct nose-to-brain drug delivery has multiple advantages, its application is limited by the extremely low delivery efficiency (<1%) to the olfactory region where drugs can enter the brain. It is crucial to developing new methods that can deliver drug particles more effectively to the olfactory region. Materials and methods We introduced a delivery method that used magnetophoresis to improve olfactory delivery efficiency. The performance of the proposed method was assessed numerically in an image-based human nose model. Influences of the magnet layout, magnet strength, drug-release position, and particle diameter on the olfactory dosage were examined. Results and discussion Results showed that particle diameter was a critical factor in controlling the motion of nasally inhaled ferromagnetic drug particles. The optimal particle size was found to be approximately 15 μm for effective magnetophoretic guidance while avoiding loss of particles to the walls in the anterior nose. Olfactory delivery efficiency was shown to be sensitive to the position and strength of magnets and the release position of drug particles. The results of this study showed that clinically significant olfactory doses (up to 45%) were feasible using the optimal combination of magnet layout, selective drug release, and microsphere-carrier diameter. A 64-fold-higher delivery of dosage was predicted in the magnetized nose compared to the control case, which did not have a magnetic field. However, the sensitivity of olfactory dosage to operating conditions and the unstable nature of magnetophoresis make controlled guidance of nasally inhaled aerosols still highly challenging.

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Modeling of release position and ventilation effects on olfactory aerosol drug delivery

Cited by 66 publications

References 57 publications

Growth of Nasal and Laryngeal Airways in Children: Implications in Breathing and Inhaled Aerosol Dynamics

Growth of Nasal and Laryngeal Airways in Children: Implications in Breathing and Inhaled Aerosol Dynamics

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

Improving intranasal delivery of neurological nanomedicine to the olfactory region using magnetophoretic guidance of microsphere carriers

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