Aerosolized liposomal

Several groups investigated the use of liposomes for the intra-pulmonary delivery. Farr et al. (1985) showed that the deposition of aerosolized liposomes in the human lung depends on the aerosol particle size. Short-term retention profiles for MLVs and SUVs deposited in the lung were indicative of clearance via the mucociliary transport mechanism. 

In the same study, the researchers did not detect AmB in serum or other organs, indicating that the liposomes achieved pulmonary targeting for the drug. However, it has also been observed in other studies that aerosolized liposomal AmB can be effective against systemic Cryptococcus and Candida infections, indicating that the aerosolized drug can be absorbed sufficiently to reach therapeutic systemic concentrations [91, 94],... 

B. E. Gilbert, P. R. Wyde, and S. Z. Wilson, Aerosolized liposomal amphotericin B for treatment of pulmonary and systemic Cryptococcus neoformans infections in mice, Antimicrob. Agents Chemother. 36 1466 (1992). 

S. D. Allen, K. N. Sorensen, M. J. Nejdi, C. Durrant, and R. T. Proffit, Prophylactic efficacy of aerosolized liposomal (AmBisome) and non-liposomal (Fungizone) amphotericin B in murine pulmonary aspergillosis,./. Antimicrob. Chemother. 34 1001... 

Verschraegen, C. F, Gilbert, B. E., Loyer, E., Huaringa, A., Walsh, G., Newman, R. A., et al. (2004), Clinical evaluation of the delivery and safety of aerosolized liposomal 9-nitro-20(s)-camptothecin in patients with advanced pulmonary malignancies, Clin. Cancer Res., 10, 2319-2326. 

Slobbe L, Boersma E, Rijnders BJ. Toler-abihty of prophylactic aerosolized liposomal amphotericin-B and impact on pulmonary function data from a randomized placebo-controlled trial. Pulm Pharmacol Ther 2008 21 855-9. 

For the treatment of lung surfactant deficiency in premature human infants suffering from respiratory distress syndrome, limited clinical trials were performed showing that liposomes in the lung-instilled intratracheally either as an aerosolized mist (Ivey et al., 1977) or as a suspension via an endotracheal tube (Fujiwara et al., 1980)—rapidly improved lung function. No adverse effects were observed as a result of the supplementation with surfactant-like material. It appears, therefore, that liposomes are a suitable system for the delivery of major phospholipid components of endogenous lung surfactant. 

Schreier H, Gagne L, Conary JT, Laurian G (1998) Simulated lung transfection by nebulization of liposome cDNA complexes using a cascade impactor seeded with 2-CFSMEO-cells. J Aerosol Med 11 1-13... 

Vidgren, M.T., Waldrep, J.C., Arppe, J., Blaek, M., Rodarte, J.A., Cole, W., and Knight, V., A study of teehnetium-labelled beelomethasone dipropionate dilauroylphospatidyleholine liposome aerosol in normal volunteers, Int. J. Pharm., 115 209-216 (1995). 

Several vectors have been used in an attempt to deliver the cf gene to the airway epithelial cells of sufferers. The most notable systems include adenoviruses and cationic liposomes. Vector delivery to the target cells can be achieved directly by aerosol technology. Delivery of cftr cDNA to airway epithelial cells (and subsequent gene expression) has been demonstrated with the use of both vector types. However, in order to be of therapeutic benefit, it is essential that 5-10% of the target cell population receive and express the cftr gene. This level of integration has not been... 

Answer Aerosol delivery of the CFTR gene. Both viruses and liposome-DNA complexes are capable of successful CFTR gene transfer to the nasal and airway epithelia of patients with CF. In fact, gene transfer to the airways is one of the few areas where liposome-DNA complexes match the expression obtained using viral vectors without the viruses inflammatory side effects. Current trials are aimed at optimizing gene delivery with reduced toxicity to produce sustained correction of the epithelial transport defect. 

Anticancer effect of 9-nitrocamptothecin liposome aerosol on human cancer xenografts in nude mice. Cancer Chemother. Pharmacol. 44 177-186. 

Densmore, C.L., Giddings, T.H., Waldrep, J.C., Kinsey, B.M. and Knight, V. (1999) Gene transfer by guanidinium-cholesterol Dioleoylphosphatidyl-ethanolamine liposome-DNA complexes in aerosol. J. Gene. Med., 1,251-264. 

B. E. Gilbert, and V. Knight, Pulmonary delivery of antiviral drugs in liposome aerosols, Semin. Pediatr. Infer. Dis. 7 148 (1996). 

M. Vidgren, J. C. Waldrep, J. Arppe, M. Black, J. A. Rodarte, W. Cole, and V. Knight, A study of " technetium-labelled beclomethasone dipropionate dilauroyl-phosphatidlycholine liposome aerosol in normal volunteers, Int. J. Pharm. 115 209... 

J. Conley, H. Yang, T. Wilson, K. Blasetti, V. D. Ninno, G. Schnell, and J. P. Wong, Aerosol delivery of liposome-encapsulated ciprofloxacin aerosol characterization and efficacy against Francisella tularensis infection in mice, Antimicrob. Agents Chemother. 47 1288 (1997). 

---