Polysaccharide-Coated Liposomal Amphotericin B for the Treatment of Murine Pulmonary Candidiasis.

Abstract

M., SATO, T. and SUNAMOTO, J. Polysaccharide-Coated Liposomal Amphotericin B for the Treatment of Murine Pulmonary Candidiasis. Tohoku J. Exp. Med., 1992, 168 (3), [483][484][485][486][487][488][489][490] Amylopectin-coated liposomal amphotericin B was investigated in a murine model of pulmonary candidiasis. The LD50 of amylopectincoated liposomal amphotericin B in normal mice was more than 10.0 mg/kg, and that of conventional amphotericin B was 1.2 mg/kg. Amylopectin-coated liposomes showed twice the concentration in the lungs of conventional liposomes. Candida albicans was inoculated intratracheally into BALB/C mice. Twentyfour hours later, the number of Candida in the lungs of mice treated with amylopectin-coated liposomes was less than in those treated with conventional liposomes, and amylopectin-coated liposomes improved the survival rate of inoculated mice. Coating liposomes with amylopectin aids the targeting of amphotericin B to the lungs. liposome ; amphotericin B ; amylopectin ; pulmonary candidiasis ; HPLC Encapsulation of amphotericin B with liposomes decreases its toxicity (Graybill et al. 1982;Lopez-Berestein et al. 1984b). We also confirmed reduced toxicity and increased efficacy of liposomal amphotericin B in murine candidiasis (Miyazaki et al. 1990). Liposomes distribute mainly in the reticuloendothelial systems, but coating liposomes with polysaccharide reduced the distribution. Takada and co-workers reported that polysaccharide-coated liposomes distributed more preferentially in the lungs than conventional liposomes (Takada et al. 1984). In the present study, the higher concentrations of polysaccharide-coated liposomes in lungs suggested their therapeutic efficacy in respiratory infection. We used these polysaccharide-coated liposomes as an amphotericin B carrier for the therapy of murine pulmonary candidiasis.

Mini review on emerging methods of preparation of liposome and its application as Liposome drug delivery systems

“…The alveolar macrophages selectively sequester the O-palmitoyl amylopectin anchored liposomes. The macrophage cuptake have been confi rmed with the help of fl uorescent probe marker, as marker was traced mainly in macrophages after IV injection [110]. Moreover, OPA anchored liposomes are reported to be sequestered and retained selectively in lungs by anionic-scavenging receptors [110][111].…”

“…Myocet™ provides a limited degree of prolonged circulation as likened with free drug. However, the liposome encapsulation signifi cantly alters the bio-distribution of doxorubicin, resulting in some reduction in toxicities [110].…”

“…The molecule that the polymer will sense is used as a template around which the monomers are allowed to polymerize. The template molecule is then extracted from the polymer [110][111].…”

“…The macrophage cuptake have been confi rmed with the help of fl uorescent probe marker, as marker was traced mainly in macrophages after IV injection [110]. Moreover, OPA anchored liposomes are reported to be sequestered and retained selectively in lungs by anionic-scavenging receptors [110][111]. Liposomes appended with O-palmitoylpullulan (OPP) and O-palmitoyl amylopectin (OPA) are swiftly cleared from the blood as compared to `naked' liposomes.…”

“…However, they have a relatively wide tissue circulation including liver and spleen, it's found that OPA anchored liposomes are selectively intercepted sequestered and internalized by the lung macrophages and monocytes. Subsequent to this observation, investigations were made on OPA anchored liposomes to explore their potential as a delivery system for sisomycin treatment of lung diseases in guinea pigs infected with Legionella pneumophila [110]. The therapeutically benefi cial results of these studies subsequently promoted further investigations, where OPA anchored liposomes were tested for targeted delivery of antimicrobial agents against intracytoplasmic pathogens and fungus.…”