Acute Effects of Liposome Aerosol Inhalation on Pulmonary Function in Healthy Human Volunteers

Thomas, Dwayne A.; Myers, Mark A.; Wichert, Birgit M.; Schreier, Hans; Gonzalez‐Rothi, Ricardo J.

doi:10.1378/chest.99.5.1268

Cited by 83 publications

(27 citation statements)

References 10 publications

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“…To the best of our knowledge, no studies of the effect of cationic liposomes on the human respiratory epithelium in vivo have been reported. Our findings are in accord with a previous study showing that phosphatidylcholine, a neutral liposome, has no acute deleterious effect on lung function as measured by spirometry in 10 human subjects [12].…”

Section: Discussionsupporting

confidence: 93%

Nasal application of the cationic liposome DC-Chol:DOPE does not alter ion transport, lung function or bacterial growth

Middleton¹,

Caplen²,

Gao³

et al. 1994

Eur Respir J

107

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Liposome-mediated gene transfer is commonly used for in vitro transfection of deoxyribonucleic acid (DNA) into mammalian cells. We and others have recently demonstrated that this can be an effective method for in vivo delivery of plasmid DNA containing the human cystic fibrosis transmembrane conductance regulator (CFTR) gene to mouse models of cystic fibrosis (CF). This suggests that cationic liposomes may be useful for transferring CFTR complementary DNA (cDNA) into the airways of CF subjects. In such trials, measurement of nasal potential difference (PD) will be used to monitor the efficacy of correction of the CF bioelectric defect and to provide a sensitive assay of epithelial integrity [corrected]. We therefore assessed whether the cationic liposome DC-Chol: DOPE altered nasal ion transport parameters, in six normal and three CF subjects. Lung function was also measured as a further marker of safety. Finally, as CF airways are chronically infected, we studied whether DC-Chol:DOPE or DC-Chol:DOPE-DNA complexes altered the bacterial growth and sensitivities of CF sputum. No significant effect was seen on any of these parameters, suggesting that DC-Chol:DOPE may be appropriate for use in human trials of liposome-mediated gene therapy for CF.

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Section: Discussionsupporting

confidence: 93%

Nasal application of the cationic liposome DC-Chol:DOPE does not alter ion transport, lung function or bacterial growth

Middleton¹,

Caplen²,

Gao³

et al. 1994

Eur Respir J

107

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“…This adminispatients after administration of GL-67A, but both these (anti-nuclear factor and anti-cytoskeletal antibody) are tration procedure was well tolerated and forms a basis for our forthcoming CF trial. commonly found in healthy people 14 and also bore no relation to dose, with the positive anti-cytoskeletal antiThis study is the first to assess the safety of nebulis-ation of an aerosol formulation of a cationic lipid into the planned administration of lipid in order to exclude any 15.5 subject with a fall in FEV 1 of Ͼ20% as a result of the challenge. The study was approved by the Ethics Com-…”

Section: Discussionmentioning

confidence: 99%

Safety of a single aerosol administration of escalating doses of the cationic lipid GL-67/DOPE/DMPE-PEG5000 formulation to the lungs of normal volunteers

Chadwick¹,

Kingston

Stern³

et al. 1997

Gene Ther

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Several groups are assessing the use of cationic lipids for administration and at intervals up to 21 days thereafter. respiratory gene therapy. To date no human data are availNo adverse clinical events were seen or any statistically able regarding the safety of intra-pulmonary cationic lipid significant changes in spirometry or gas transfer. There delivery. In preparation for a trial of pulmonary delivery of were no clinically significant changes in any of the blood the CFTR gene, we have assessed the safety of nebulised parameters and no CT changes were seen. Comparisons lipid GL-67/DOPE/DMPE-PEG 5000 (GL-67A), the cationic of the cellular subpopulations (neutrophils, eosinophils, lipid formulation to be used in this study. Fifteen healthy lymphocytes and macrophages) in induced sputum volunteers were given incremental doses of GL-67A via a showed no significant alterations following administration Pari LC Jet nebuliser; three volunteers in each of five dosof the GL-67A. This study suggests that a single appliing cohorts with a week interval between cohorts. Markers cation of aerosol formulation of GL-67A does not result in of safety included clinical assessment, measurement of clinically detectable changes when given by nebulisation lung function, chest CT scan, serological testing and analyinto the lungs of normal volunteers and provides an indisis of induced sputum. Measurements were taken before cation of a lipid dose tolerated in man.

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“…Host inflammatory or immune response to this ligand is not expected to occur. Recent results of the toxicity study of liposomes following their delivery to the lungs of human 32 and animals 33,34 showed minimal to no host inflammatory response. Therefore, we do not anticipate significant adverse immunological or inflammatory response to our transfection vector when applied in vivo.…”

Section: Discussionmentioning

confidence: 99%

Effects of epidermal growth factor, transferrin, and insulin on lipofection efficiency in human lung carcinoma cells

Yanagihara

Cheng²,

Cheng³

2000

Cancer Gene Ther

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Poor transfection efficiency is the major drawback of lipofection. We showed previously that addition of transferrin (TF) to Lipofectin enhanced the expression of a reporter gene in HeLa cells by 120-fold and achieved close to 100% transfection efficiency. The purpose of this study was to determine whether TF and other ligands could improve the efficiency of lipofection in lung carcinoma cells. Confluent A549, Calu3, and H292 cells were transfected for 18 hours with a plasmid DNA (pCMVlacZ) using Lipofectin plus TF, insulin, or epidermal growth factor as the vector. The transfected cells were assessed for transfection efficiency by ␤-galactosidase activity (light units/g protein) and the percentage of blue cells following 5-bromo-4-chloro-3-indolyl ␤-Dgalactopyranoside staining. Lipofectin supplemented with epidermal growth factor yielded the largest enhancement of lipofection efficiency (Յ23-fold over that by Lipofectin alone) in all three cell lines. Insulin significantly enhanced the lipofection efficiency in A549 and Calu3 cells but not in H292 cells, whereas TF showed significant lipofection efficiency-enhancing effect in Calu3 and H292 cells but not in A549 cells. The transfection efficiency correlated well with the amounts of DNA delivered to the nucleus as well as the amounts of the receptor. These results indicate that the gene delivery strategy employing ligand-facilitated lipofection can achieve high transfection efficiency in human lung carcinoma cells. In addition, enhancement of the expression of the receptor may be a possible strategy for increasing the efficiency of gene targeting. Cancer Gene Therapy (2000) 7, 59 -65

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Acute Effects of Liposome Aerosol Inhalation on Pulmonary Function in Healthy Human Volunteers

Cited by 83 publications

References 10 publications

Nasal application of the cationic liposome DC-Chol:DOPE does not alter ion transport, lung function or bacterial growth

Nasal application of the cationic liposome DC-Chol:DOPE does not alter ion transport, lung function or bacterial growth

Safety of a single aerosol administration of escalating doses of the cationic lipid GL-67/DOPE/DMPE-PEG5000 formulation to the lungs of normal volunteers

Effects of epidermal growth factor, transferrin, and insulin on lipofection efficiency in human lung carcinoma cells

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