Protective effect of a muramyl dipeptide analog encapsulated in or mixed with liposomes against Candida albicans infection

Encapsulation of N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine in multilamellar vesicles composed of phosphatidylcholine, cholesterol, and phosphatidylserine (7:6.7:3) or phosphatidylcholine and phosphatidylserine (7:3) reduced the amount of drug needed to protect against a Candida albicans intravenous infection. The 50% effective doses for encapsulated and free drug were 5.5 and greater than 80 mg/kg, respectively. The optimum treatment was twice (at days 4 and 2 preinfection) by the intravenous route. Intraperitoneal, subcutaneous, and oral routes of administration were ineffective. The same potentiation of anti-Candida activity was observed whether the lower dose of drug was encapsulated in multilamellar vesicles, mixed with multilamellar vesicles, or given either 1 h before or 1 h after multilamellar vesicles. It was postulated that the mechanism of action involved the retention of the liposomes by organs of the reticuloendothelial system, resulting in an enhanced response of the macrophages to the immunostimulating activity of the N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine given in conjunction with the vesicles.

[1]  W. Stewart,et al.  Altered pharmacological properties of liposome-associated human interferon-alpha. , 1982, Journal of virology.

[2]  I. Fidler,et al.  Involvement of macrophages in the eradication of established metastases following intravenous injection of liposomes containing macrophage activators. , 1982, Cancer research.

[3]  E. Fraser-Smith,et al.  Correlation between in vivo anti-Pseudomonas and anti-Candida activities and clearance of carbon by the reticuloendothelial system for various muramyl dipeptide analogs, using normal and immunosuppressed mice , 1982, Infection and immunity.

[4]  E. Fraser-Smith,et al.  Protective effect of muramyl dipeptide analogs against infections of Pseudomonas aeruginosa or Candida albicans in mice , 1981, Infection and immunity.

[5]  I. Fidler,et al.  Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[6]  I. Fidler,et al.  In vitro activation of tumoricidal properties in rat alveolar macrophages by synthetic muramyl dipeptide encapsulated in liposomes. , 1981, Cellular immunology.

[7]  R. Johnston,et al.  Activation of macrophages for enhanced release of superoxide anion and greater killing of Candida albicans by injection of muramyl dipeptide , 1980, Journal of Experimental Medicine.

[8]  R. Rutman,et al.  Relative enhancement by various liposomes of BCNU effectiveness against L-1210 leukemia in vivo. , 1980, Research communications in chemical pathology and pharmacology.

[9]  L. Chedid,et al.  Components of mycobacteria and muramyl dipeptide with adjuvant activity induce lymphocyte activating factor. , 1980, Cellular immunology.

[10]  R. Johnston,et al.  Increased production of superoxide anion by macrophages exposed in vitro to muramyl dipeptide or lipopolysaccharide , 1980, The Journal of experimental medicine.

[11]  R. W. Ferraresi,et al.  Muramyl dipeptide stimulation of particle clearance in several animal species. , 1980, Journal of the Reticuloendothelial Society.

[12]  T. Taniyama,et al.  Direct augmentation of cytolytic activity of tumor-derived macrophages and macrophage cell lines by muramyl dipeptide. , 1979, Cellular immunology.

[13]  S. Kusumoto,et al.  Macrophage activation by bacterial cell walls and related synthetic compounds , 1979, Infection and immunity.

[14]  S. Wahl,et al.  Macrophage activation by mycobacterial water soluble compounds and synthetic muramyl dipeptide. , 1979, Journal of immunology.

[15]  S. Kusumoto,et al.  Stimulation of the reticuloendothelial system of mice by muramyl dipeptide , 1979, Infection and immunity.

[16]  E. Lederer,et al.  Fate of the synthetic immunoadjuvant, muramyl dipeptide (14C-labelled) in the mouse. , 1979, International journal of immunopharmacology.

[17]  J. Hadden,et al.  The comparative effects of isoprinosine, levamisole, muramyl dipeptide and SM1213 on lymphocyte and macrophage proliferation and activation in vitro. , 1979, International journal of immunopharmacology.

[18]  G. Weissmann,et al.  The introduction of enzymes into cells by means of liposomes. , 1978, Journal of lipid research.

[19]  S. Nagao,et al.  Inhibition of macrophage migration by synthetic muramyl dipeptide. , 1978, Biochemical and biophysical research communications.

[20]  H. Kimelberg,et al.  PROPERTIES AND BIOLOGICAL EFFECTS OF LIPOSOMES AND THEIR USES IN PHARMACOLOGY AND TOXICOLOGY , 1978 .

[21]  J. Weinstein,et al.  Interactions of liposomes with mammalian cells. , 1978, Annual review of biophysics and bioengineering.

[22]  L. Chedid,et al.  Comparison between macrophage activation and enhancement of nonspecific resistance to tumors by mycobacterial immunoadjuvants. , 1975, Proceedings of the National Academy of Sciences of the United States of America.