Document Detail

Delivery of superoxide dismutase to pulmonary epithelium via pH-sensitive liposomes.
MedLine Citation:
PMID:  7900818     Owner:  NLM     Status:  MEDLINE    
Respiratory insufficiency, when treated with oxygen supplementation, or exposure to diverse pulmonary toxins can cause lung damage as a result of increased oxygen radical production. Enzymes such as superoxide dismutase (SOD) may attenuate this pathological process, but the intracellular delivery and antioxidant action of SOD is impeded by its inability to cross cellular membranes. One approach for facilitating intracellular delivery of macromolecules is to entrap SOD into liposomes. The delivery of SOD to lung cells was accomplished using pH-sensitive liposomes, made with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and 1-oleoyl-2-oleoyl-sn-glycero-3-succinate (DOSG), added to cultured fetal rat lung distal epithelial (FRLE) cells. FRLE cells, obtained from fetuses at day 19 gestation, expressed a high-affinity receptor for surfactant protein A (SP-A) with an apparent dissociation constant (Kd) = 3.6 +/- 0.2 micrograms/ml (5.5 x 10(-9) M) and a capacity of 130 +/- 3 ng/10(6) cells (125,000 +/- 3,000 binding sites/cell). This receptor was utilized for targeting liposomes to cells, after incorporating SP-A during liposome membrane formation. Liposomes were uniformly small (180 +/- 77 nm; mean +/- SD) and stable at 4 degrees C for 1 wk, entrapping 10 +/- 4% of initially added SOD. After incubation of pH-sensitive liposomes containing entrapped SOD with cultured FRLE cells, cell-associated SOD activity was increased 5.1-fold from 7.8 +/- 2.5 to 40.1 +/- 3.3 U SOD/mg cell protein. Incorporation of SP-A into liposomes increased by 6.2-fold the delivery of liposomal SOD to cells.(ABSTRACT TRUNCATED AT 250 WORDS)
P Briscoe; I Caniggia; A Graves; B Benson; L Huang; A K Tanswell; B A Freeman
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The American journal of physiology     Volume:  268     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1995 Mar 
Date Detail:
Created Date:  1995-04-25     Completed Date:  1995-04-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  L374-80     Citation Subset:  IM    
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 35233.
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MeSH Terms
Cells, Cultured
Drug Carriers
Embryo, Mammalian
Epithelium / enzymology
Gestational Age
Hydrogen-Ion Concentration
Lung / enzymology*
Proteolipids / metabolism
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactant-Associated Proteins
Pulmonary Surfactants / metabolism
Superoxide Dismutase / administration & dosage*
Reg. No./Substance:
0/Drug Carriers; 0/Liposomes; 0/Phosphatidylethanolamines; 0/Proteolipids; 0/Pulmonary Surfactant-Associated Protein A; 0/Pulmonary Surfactant-Associated Proteins; 0/Pulmonary Surfactants; 0/Triglycerides; 129445-40-5/1,2-dioleoyl-3-succinylglycerol; 76391-83-8/1,2-dielaidoylphosphatidylethanolamine; EC Dismutase

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