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

Xi J, Zhang Z, Si XA - Int J Nanomedicine (2015)

Bottom Line: It is crucial to developing new methods that can deliver drug particles more effectively to the olfactory region.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.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.

View Article: PubMed Central - PubMed

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

ABSTRACT

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.

No MeSH data available.


Human nose model and the olfactory region.Notes: The red circle highlights where the olfactory region is located. (A). For optimal olfactory drug delivery, particles should travel along the middle plane (B) of the nasal passage, which exhibits complex spatial features.Abbreviations: IM, inferior meatus; LP, lower passage; MM, middle meatus; MRI, magnetic resonance imaging; OR, olfactory region; SM, superior meatus; UP, upper passage.
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f1-ijn-10-1211: Human nose model and the olfactory region.Notes: The red circle highlights where the olfactory region is located. (A). For optimal olfactory drug delivery, particles should travel along the middle plane (B) of the nasal passage, which exhibits complex spatial features.Abbreviations: IM, inferior meatus; LP, lower passage; MM, middle meatus; MRI, magnetic resonance imaging; OR, olfactory region; SM, superior meatus; UP, upper passage.

Mentions: Direct nose-to-brain drug delivery provides a noninvasive method that bypasses the blood–brain barrier and directly delivers medication to the brain and spinal cord.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). The olfactory region is located above the superior turbinate (Figure 1A), and covers about 8% of the surface area of the nasal passage.6 Due to the labyrinth structure of the nasal passage, most inhaled particles will be trapped by the nasal wall and filtered out (Figure 1B). Conventional inhalation devices depend on inspiratory aerodynamics to transport therapeutic agents to the target area.7 There is no further control on the motions of particles after their release. Therefore, the transport and deposition of these particles predominantly depend on their initial velocity. Due to the convoluted nasal passage, as well as the lack of particle control, the majority of drug particles are trapped in the anterior nose and cannot reach the targeted olfactory region.


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

Xi J, Zhang Z, Si XA - Int J Nanomedicine (2015)

Human nose model and the olfactory region.Notes: The red circle highlights where the olfactory region is located. (A). For optimal olfactory drug delivery, particles should travel along the middle plane (B) of the nasal passage, which exhibits complex spatial features.Abbreviations: IM, inferior meatus; LP, lower passage; MM, middle meatus; MRI, magnetic resonance imaging; OR, olfactory region; SM, superior meatus; UP, upper passage.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4334328&req=5

f1-ijn-10-1211: Human nose model and the olfactory region.Notes: The red circle highlights where the olfactory region is located. (A). For optimal olfactory drug delivery, particles should travel along the middle plane (B) of the nasal passage, which exhibits complex spatial features.Abbreviations: IM, inferior meatus; LP, lower passage; MM, middle meatus; MRI, magnetic resonance imaging; OR, olfactory region; SM, superior meatus; UP, upper passage.
Mentions: Direct nose-to-brain drug delivery provides a noninvasive method that bypasses the blood–brain barrier and directly delivers medication to the brain and spinal cord.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). The olfactory region is located above the superior turbinate (Figure 1A), and covers about 8% of the surface area of the nasal passage.6 Due to the labyrinth structure of the nasal passage, most inhaled particles will be trapped by the nasal wall and filtered out (Figure 1B). Conventional inhalation devices depend on inspiratory aerodynamics to transport therapeutic agents to the target area.7 There is no further control on the motions of particles after their release. Therefore, the transport and deposition of these particles predominantly depend on their initial velocity. Due to the convoluted nasal passage, as well as the lack of particle control, the majority of drug particles are trapped in the anterior nose and cannot reach the targeted olfactory region.

Bottom Line: It is crucial to developing new methods that can deliver drug particles more effectively to the olfactory region.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.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.

View Article: PubMed Central - PubMed

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

ABSTRACT

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.

No MeSH data available.