Document Detail


Concepts on the use of liposomal antimicrobial agents: applications for aminoglycosides.
MedLine Citation:
PMID:  1420679     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Liposomes are microscopic lipid vesicles consisting of one or more concentric phospholipid bilayers enclosing discrete aqueous spaces. Liposomes provide an apparently nontoxic biological delivery system for hydrophobic and hydrophilic drugs. With few exceptions liposomal antimicrobial drugs are administered intravenously, although other routes have been investigated. Intravenously administered, conventionally prepared vesicles are rapidly cleared from the blood principally by phagocytic cells of the mononuclear phagocyte system (MPS), in particular by macrophages located in the liver (Kupffer's cells) and spleen. The expectation that liposomes would provide a new form of drug carrier capable of diverse physiological selectivity has not been realized. The low endocytotic capacity of many cell types and the inability of liposomes to transverse continuous vascular endothelia have prevented the active targeting of non-MPS tissues with liposomes. Despite their well-documented toxicity and the development of new antimicrobial classes, aminoglycosides continue to have an important antimicrobial role. The encapsulation of aminoglycosides into liposomes may reduce the toxicity associated with the multiple daily administration often required for patients with normal renal function. In addition, the encapsulation of aminoglycosides alters their pharmacokinetics, increases t1/2 and area under the curve, decreases Vd and Cpmax, and causes a shift in drug accumulation from the kidney to other organs, thus potentially reducing nephrotoxicity. Studies demonstrate improved outcome for intracellular infections treated with liposomal aminoglycosides vs. free aminoglycosides. Unresolved questions include what role liposomal aminoglycosides have in the treatment of extracellular infection and whether their sustained release action will promote resistance.
Authors:
J A Karlowsky; G G Zhanel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America     Volume:  15     ISSN:  1058-4838     ISO Abbreviation:  Clin. Infect. Dis.     Publication Date:  1992 Oct 
Date Detail:
Created Date:  1992-11-27     Completed Date:  1992-11-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9203213     Medline TA:  Clin Infect Dis     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  654-67     Citation Subset:  IM    
Affiliation:
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
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MeSH Terms
Descriptor/Qualifier:
Aminoglycosides
Animals
Anti-Bacterial Agents / administration & dosage*
Drug Carriers*
Humans
Infection / drug therapy*
Liposomes* / chemistry
Phospholipids / chemistry
Chemical
Reg. No./Substance:
0/Aminoglycosides; 0/Anti-Bacterial Agents; 0/Drug Carriers; 0/Liposomes; 0/Phospholipids

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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