Effects of nebulization time and pressure on lipid microtubule suspension and aerosol

Lipid microtubules have been suggested as possible drug delivery vehicles i n aerosol therapy applications. In our previous work it was shown that tubu les of respirable size were aerosolizable from a standard Collison-type air -jet nebulizer. In this work, the effects of nebulization time and pressure on lipid tubules of 1, 2-bis(10, 12-tricosadiynoyl)-sn-glycero-3-phosphoch oline (DC8,9PC) are examined. Tubules were formed in a 55 percent ethanol:w ater solution, centrifuged and washed to remove the alcohol, aerosolized at 10, 20, or 30 psi pressure for 60 min using a 3-jet Collison air jet nebul izer, and sampled into an API Aerosizer time-of-flight analyzer at 0, 1, 5, 10, 20, 30, and 60 min nebulization time. Aliquots of tubule suspension we re withdrawn from the nebulizer reservoir at the same intervals for length distribution evaluation by light microscopy. Aerosol was also sampled over the 60-min period using a Stober spiral duct centrifuge and the deposited p articles optically sized and counted to provide a time-averaged estimate of aerosol size distribution. The lipid particles were straight tubular struc tures of helically wound bilayer membranes, with 0.6 mu m diameter and log- normal length distribution. During nebulization the tubules underwent signi ficant breakage; suspension tubule lengths decreased in a predictable manne r with both increasing nebulization pressure and increasing number of passe s through the nozzle. Aerosol aerodynamic size distributions measured with the time-of-flight analyzer were essentially identical for all nebulization pressures and times, and were indistinguishable from the time-averaged siz e distributions determined from aerosol centrifuge particle deposition data . Comparison of observed aerosol size distribution with expected distributi on for an ideal air-jet nebulizer suggested that the Collison nebulizer pre ferentially aerosolized shorter tubules, consistent,vith known air-jet nebu lizer operation. These results demonstrate that while lipid tubules undergo substantial resizing during nebulization, the resulting aerosol size distr ibution is stable and of respirable size for at least 60 min nebulization t ime.