Question

1. Which region of the lungs is the desired site of particle deposition (oropharynx, conducting airways, or peripheral airways)?

2. List 3 reasons why the respiratory membranes make an ideal site for systemic drug absorption.

3. Are most drugs that are delivered via the pulmonary route used to treat local (pulmonary) disease or non-local (systemic) disease?

4. What are 3 advantages of pulmonary drug delivery for treatment of pulmonary disease?

5. Define the 3 mechanisms of particle deposition in the lung (inertial impaction, sedimentation, and diffusion).

6. Categorize particle size according to :
   1. Mechanism of particle deposition

2. Region of particle deposition

Answer 1

Ans 1: In the respiratory tract, the particles get deposited in oropharyngeal region.

Ans 2: The nasal epithelial membrane is the ideal site for absorption of drugs because

Small hydrophobic molecules can partition across biological membranes via a concentration gradient.

Hydrophilic molecules generally require some sort of selective transport system to cross the lipid bilayer.

Large and polar drugs may be absorbed by a paracellular mechanism, and the tight junction structure represents the barrier to paracellular absorption.

Ans 3: Drug delivery to the respiratory area can also be used for systemic delivery of peptides and proteins due to the large surface area for drug absorption. Liposomes and phospholipids have been investigated for the systemic absorption of proteins after intra tracheal administration. The use of absorption enhancers increases systemic absorption of biomolecules.

Ans 4: Advantage of pulmonary drug delivery for treatment of pulmonary disease

(a) reduced size and increased surface to volume ratio,

(b) high drug-loading efficiency

(c) efficient absorbance to the lung epithelium and avoidance of pulmonary clearance make inhaled nanoparticles an ideal drug delivery approach.

Ans 5: Mechanisms of particle deposition in the lung

(A) Mechanism of particle deposition

(a) Inertial impaction

Inertial impaction affects mainly particles that are larger than 5 μm and refers to the particle's inability to follow sudden change in gas flow direction such as in the upper airway and at airway bifurcations. Each time the flow changes direction, the momentum of the particles tends to keep them on their existing trajectories, causing the particles to deviate from the air streamlines and to eventually impact on airway walls.

(b) Gravitational sedimentation

Gravitational sedimentation refers to the settling of particles under the action of gravity and occurs mainly in small airways and alveolar cavities where the distance to be covered by the particles before touching the walls is small.

(c) Brownian diffusion

Deposition by Brownian diffusion results from the random motions of the particles caused by their collisions with gas molecules and is most effective in the acinar region of the lung where air velocities are low. The deposition by Brownian diffusion increases with decreasing particle size and becomes the dominant mechanism of deposition for particles less than 0.5 μm in diameter.

(B) Region of particle deposition

(a) Electrostatic precipitation

Electrically charged particles close to airways surfaces induce image charges on the surface. Charged particles are then electrostatically attracted to the airway walls, and as a consequence, deposition of charged particles may be greater than that of neutral particles.

(b) Interception

Interception is the mechanism by which particles, while following the mainstream flow, come into contact with an airway wall because of their shape and size.

(c) Turbulent mixing

Turbulent mixing affects aerosol deposition mainly in the upper respiratory tract and the large airways. Such mixing refers to the irregular fluctuations or mixing undergone by the fluid in a turbulent regime, which cause the fluid speed and therefore the trajectories of particles to continuously undergo changes in both magnitude and direction and to eventually deposit on airway walls.