title: Ligand directed macrophage targeting of amphotericin B loaded liposomes.
abstract: Two types of ligand anchored multilamellar liposomes (MLVs) containing amphotericin B (Amp B) were prepared. The MLVs consisting of soya phosphatidylcholine (PC) and cholesterol (Chol) were coated with O-palmitoyl mannan (OPM). Similarly, the MLVs with the same Amp B content consisting of soya PC, Chol and phosphatidylethanolamine (PE) were prepared and covalently anchored with p-aminophenyl-mannopyranoside (PAM). The surface modified MLVs and their plain counterparts were characterised for size, shape, lamellarity, entrapment efficiency and ligand density. The stability in serum and in vivo bio-distribution in albino rats were also determined. It was observed that extent of accumulation of liposomal Amp B in macrophage rich organs, particularly liver, spleen and lungs was significantly high when compared against the free drug. The rates and extent of accumulation were found to increase further on ligand anchoring. In either of the cases, the macrophagic uptake of ligand anchored liposomes was inhibited significantly on pre-injection of hydrolysed mannan, being suggestive of receptor mediated uptake of ligand anchored liposomes. Comparison of biodistruibution pattern of ligand anchored MLVs revealed that PAM linked liposomes exhibited a higher hepato-splenic accumulation where as drug accumulation in lungs was highest in the case of OPM coated liposomes. It was thus observed that mannopyranoside is a specific ligand for targeting bioactives to the macrophages of liver and spleen while OPM could preferentially negotiate the targeting of bioactives to the alveolar macrophages.
authors.affiliation: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr H.S. Gour Vishwavidyala, Sagar, MP, India. spvyas@bom6.vsnl.net.in
authors.forename: S P
authors.initials: SP
authors.lastname: Vyas
authors.forename: Y K
authors.initials: YK
authors.lastname: Katare
authors.forename: V
authors.initials: V
authors.lastname: Mishra
authors.forename: V
authors.initials: V
authors.lastname: Sihorkar
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D002784:Cholesterol / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D004553:Electric Conductivity; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D008024:Ligands; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D008351:Mannans; D010169:Palmitic Acids; D010316:Particle Size; D051381:Rats; D014018:Tissue Distribution
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D008024:Ligands; D008081:Liposomes; D008351:Mannans; D010169:Palmitic Acids; D000666:Amphotericin B; D002784:Cholesterol