CONCEPTS ON THE USE OF LIPOSOMAL ANTIMICROBIAL AGENTS - APPLICATIONS FOR AMINOGLYCOSIDES

被引:59
作者
KARLOWSKY, JA
ZHANEL, GG
机构
[1] UNIV MANITOBA,FAC MED,DEPT MED MICROBIOL,WINNIPEG R3T 2N2,MANITOBA,CANADA
[2] UNIV MANITOBA,FAC PHARM,WINNIPEG R3T 2N2,MANITOBA,CANADA
关键词
D O I
10.1093/clind/15.4.654
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 V(d) and C(pmax), 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.
引用
收藏
页码:654 / 667
页数:14
相关论文
共 63 条
[1]  
ALLEN TM, 1984, J PHARMACOL EXP THER, V229, P267
[2]   LIPOSOMES WITH PROLONGED CIRCULATION TIMES - FACTORS AFFECTING UPTAKE BY RETICULOENDOTHELIAL AND OTHER TISSUES [J].
ALLEN, TM ;
HANSEN, C ;
RUTLEDGE, J .
BIOCHIMICA ET BIOPHYSICA ACTA, 1989, 981 (01) :27-35
[3]   ACTIVITY OF FREE AND LIPOSOME ENCAPSULATED STREPTOMYCIN AGAINST MYCOBACTERIUM-AVIUM COMPLEX (MAC) INSIDE PERITONEAL-MACROPHAGES [J].
ASHTEKAR, D ;
DUZGUNES, N ;
GANGADHARAM, PRJ .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1991, 28 (04) :615-617
[4]   DIFFUSION OF UNIVALENT IONS ACROSS LAMELLAE OF SWOLLEN PHOSPHOLIPIDS [J].
BANGHAM, AD ;
STANDISH, MM ;
WATKINS, JC .
JOURNAL OF MOLECULAR BIOLOGY, 1965, 13 (01) :238-+
[5]  
BARZA M, 1984, INVEST OPHTH VIS SCI, V25, P486
[6]   TREATMENT OF DISSEMINATED MYCOBACTERIUM-AVIUM COMPLEX INFECTION OF BEIGE MICE WITH LIPOSOME-ENCAPSULATED AMINOGLYCOSIDES [J].
BERMUDEZ, LE ;
YAUYOUNG, AO ;
LIN, JP ;
COGGER, J ;
YOUNG, LS .
JOURNAL OF INFECTIOUS DISEASES, 1990, 161 (06) :1262-1268
[7]   INTRACELLULAR KILLING OF MYCOBACTERIUM-AVIUM COMPLEX BY RIFAPENTINE AND LIPOSOME-ENCAPSULATED AMIKACIN [J].
BERMUDEZ, LEM ;
WU, M ;
YOUNG, LS .
JOURNAL OF INFECTIOUS DISEASES, 1987, 156 (03) :510-513
[8]   INTERACTIONS OF LIPOSOMES WITH SERUM-PROTEINS [J].
BONTE, F ;
JULIANO, RL .
CHEMISTRY AND PHYSICS OF LIPIDS, 1986, 40 (2-4) :359-372
[9]   KILLING OF INTRAPHAGOCYTIC STAPHYLOCOCCUS-AUREUS BY DIHYDROSTREPTOMYCIN ENTRAPPED WITHIN LIPOSOMES [J].
BONVENTRE, PF ;
GREGORIADIS, G .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1978, 13 (06) :1049-1051
[10]   LIPOSOME-ENCAPSULATED-AMIKACIN THERAPY OF MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN BEIGE MICE [J].
CYNAMON, MH ;
SWENSON, CE ;
PALMER, GS ;
GINSBERG, RS .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1989, 33 (08) :1179-1183