Lung Delivery Paper

What is the Hypothesis/premise of the paper ?

Larger porous (lower mass density) particles are more efficient in delivering therapeutics to the lungs

What were their goals?

• Produce large porous particles that have the same aerodynamic diameter as smaller, dense particles to more efficiently deliver therapeutics

• penetrate deeper into the lungs

• deliver therapeutics for a longer time

• avoid clearance mechanisms (such as macrophages)

Why larger particles ?

Smaller particles tend to aggregate more due to gravity and inertia thus larger, less dense particles overcome this barrier and break up more easily and avoid sticking to the back of the throat

In figure 1, why did they test particles with 2 different compositions?

Showed two particles with different compositions to determine that the chemistry doesn’t matter the prime determinant for higher efficiency is porosity and density

What is an important thing to note from Figure 1 when comparing PLGA and PLAL-Lys?

Showed two different profiles of the particles

• PLGA showed the internal structure of the particle thus showing cross section of the particle

• PLAL-Lys showed the polymer structure as a whole, showed the walls of the polymer

Both showed porous structure but showed different profiles of the particles thus not a good comparision

What is shown in figure 2 ?

Total particle recovery from nonporous particles vs porous particles

Why does figure 2 fail to show us and why?

Fails to prove that porous particles are efficiently delivered than nonporous b/c although the rats were administered the same mass dose the densities for each particles was different.

• porous had 0.1 density

• nonporous had 0.9 density

Thus, 10x more porous particles were administered which demonstrates no real difference in deposition efficiency

In figure 2, why did region 4 (posterior) show high levels of particle deposition?

During the experiement, the rate was laid on its back thus due to gravity the particles settled on the posterior region of the lung which was why it was so high

What is shown in figure 3 ABC?

AB: although they were administered the same mass dose

• the porous particles contained 2x the weight % than nonporous particles thus containing 2x more drug thus not showing us anything

• C: showed glucose [] vs time and did shown a rapid drop when insulin was administered but then there was rapid burst shown when it went back up

• DE: showed testosterone and wanted to see if bioavailability increased with size of porous particles but didn’t successfully support that fact

  • large standard deviations