Drug Encapsulation and Aerodynamic Behavior of a Lipid Microtubule Aerosol

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Abstract
Fibrous particles have unique aerodynamic characteristics that could be incorporated into improved aerosol therapy protocols. Lipid tubule microstructures were prepared by dissolving 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) in ethanol and diluting with water to form a 55% ethanol solution, after the method of Georger et al. (J. Am. Chem. Soc. 109:6169–6175, 1987). The resulting particles were straight tubular structures of helically wound lipid bilayer membranes, with circular cross section of outer diameter approximately 0.6 ± 0.1 μm. Tubule lengths were log-normally distributed with geometric mean 10.5 μm and s`g 1.48. Tubules were aerosolized directly from the suspension using a Collison nebulizer, and deposited on uncoated TEM grids mounted in a calibrated Stöber spiral duct aerosol centrifuge. Lengths and diameters of deposited particles were sized from photomicrographs. Particles were seen to remain straight during aerosolization and collection, but may have under-gone some fragmentation. Observed aerodynamic behavior was in agreement with predicted behavior for sedimenting cylindrical particles rotating in sheared viscous flow. Sodium cromoglycate solution was successfully encapsulated in the microtubules at efficiencies comparable to liposomes of similar aerodynamic size. These results suggest that lipid microtubules may possess the structural strength, stability, and drug encapsulation capacity necessary to serve as drug carriers in inhalation therapy applications.