Nebulized Glucocorticoids in Liposomes: Aerosol Characteristics and Human Dose Estimates

In Vitro Aerosol Delivery and Regional Airway Surface Liquid Concentration of a Liposomal Cationic Peptide

“…However, DPPC:DMPG was prone to precipitation after the typical temperature drop that takes place during nebulization, resulting in low nebulization efficiencies ( E neb = 10–30%). This effect, also found by Waldrep and coworkers,17 can be explained by the relatively high phase transition temperature of DPPC 24. The two other formulations, DLPC:DMPG and DMPC:DMPG, were less prone to precipitation and showed good nebulization efficiencies ( E neb = 30–50%).…”

“…The breakup of vesicles causes them to leak the entrapped drug back into the supernatant. Waldrep and coworkers compared the liposomal aerosols generated with different phospholipids17 and by various nebulizers,18 estimating numerically the amount deposited in each lung region. Farr et al19 and more recently Vidgren et al20 studied in vivo regional deposition and clearance of nebulized liposomes labeled with 99m‐technetium on healthy volunteers.…”

“…Another aim of the present work was to estimate the initial peptide concentration in the airway surface liquid (ASL) of human lungs21 immediately after aerosolization, to determine if efficacious levels of the drug can be expected. Because of the topical action envisioned for the CM3 peptide in the lung, an estimate of the local concentration of the antibiotic seems more relevant than the estimate of total regional dosages, obtained in previous studies 17,18,22. This concentration estimate required the combination of the measured aerosol characteristics with a mathematical lung deposition model and a new model for the ASL distribution in the human lung.…”

Gene transfer by guanidinium-cholesterol: dioleoylphosphatidyl-ethanolamine liposome-DNA complexes in aerosol

“…Generation of aerosols of liposome preparations with various drugs, DNA and various lipids, and their deposition in the respiratory tract of man and animals follow general principles. Many details of the formulation, nebulization and deposition of inhaled droplets of aerosols containing a number of different preparations of liposome‐drug preparations and of liposomes alone are described elsewhere15–18.…”

Pharmacokinetic Modeling of Systemic Uptake Following Pulmonary Delivery of a Macromolecular Drug in a Sustained Release Formulation

“…Recent recognition of the opportunities offered by pulmonary delivery of macromolecules intended for systemic action (Byron, 1990, Gupta et ai, 1991Patton et ai, 1992), justified an analysis of plasma drug levels following administration via the lung. This approach gained additional relevance with emerging interest in the use of controlled release formulations, such as liposomes, for pulmonary delivery (Michalko et al, 1988;Kellaway and Farr, 1990, Taylor and Farr, 1993, Waldrep et al, 1994 ). We have recently reported (Teitelbaum et al, 1993) that sustained plasma levels were observed for -90 hours following pulmonary delivery of a liposomal formulation of Detirelix -a synthetic, polypeptide analog of Luteinizing Hormone Releasing Hormone.…”