Liposomes as carriers of antimicrobial agents

Liposomes are microscopic vesicles consisting of multiple concentric lipid bilayers formed when an aqueous solution is added to a dried lipid film. Since their initial description by Bangham et al. (5), several types of liposomes have been characterized (41). Multilamellar liposomes or multilamellar vesicles have been extensively used as carriers of antineoplastic and antimicrobial drugs. These multilamellar vesicles have two parts: an extensive lipid compartment that embodies the multiple lipid layers and an aqueous compartment that consists of the spaces between the layers. As with most drug carriers, liposomes have been extensively used in an attempt to improve the therapeutic index of known active drugs, such as Adriamycin (14). In those studies, the major reduction observed in the target-organ toxicity of the drugs was probably related to a modification in drug distribution. Liposomes are preferentially taken up by organs rich in cells from the reticuloendothelial system. In mice (30) and humans (25), liposomes have been shown to localize in the liver, spleen, lung, and bone marrow. The biologic and pharmacologic attributes of liposomes have been exploited by several investigators for the delivery of antimicrobial agents (Table 1). Liposome type, size, lipid composition, membrane fluidity, stability and charge, and ease of preparation are factors that must be considered when designing liposomal carriers. Multilamellar vesicles with their large lipid compartment offer an advantage for the incorporation of hydrophobic drugs; in contrast, reverse evaporation vesicles are a better choice for the incorporation of hydrophilic compounds. Usually, naturally occurring, biodegradable, and nontoxic phospholipids, such as lecithin, phosphatidyl serine, and phosphatidyl glycerol, are selected. The fluidity and charge of the liposomal membranes can be altered to facilitate specific objectives, such as in the case of macrophage targeting, in which negatively charged liposomes with more fluid membranes are preferentially phagocytosed. The incorporation of sterols (ergosterol and cholesterol) increases the rigidity and stability of liposomes. However, in the case of amphotericin B (AmpB) the use of sterol-containing liposomes results in decreased antifungal activity. This latter observation is probably related to tight drug-sterol binding which impedes the exchange of the drug with fungal membranes.