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Ligand directed macrophage targeting of amphotericin B loaded liposomes
S P Vyas1, Y K Katare, V Mishra
1Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr H.S. Gour Vishwavidyala, Sagar, MP, India. spvyas@bom6.vsnl.net.in
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.
Insights
Ligand-anchored liposomes containing amphotericin B show enhanced accumulation in macrophage-rich organs. Mannopyranoside targets liver and spleen, while O-palmitoyl mannan targets lung macrophages.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Nanotechnology
Background:
- Liposomes are effective drug delivery systems.
- Targeting liposomes to specific organs can improve drug efficacy and reduce side effects.
- Amphotericin B is a potent antifungal drug with significant toxicity.
Purpose of the Study:
- To prepare and characterize ligand-anchored multilamellar liposomes (MLVs) containing amphotericin B (Amp B).
- To evaluate the in vivo biodistribution and targeting potential of these modified liposomes.
- To compare the targeting efficiency of two different mannose-based ligands: O-palmitoyl mannan (OPM) and p-aminophenyl-mannopyranoside (PAM).
Main Methods:
- Preparation of MLVs composed of soya phosphatidylcholine (PC), cholesterol (Chol), and phosphatidylethanolamine (PE).
- Surface modification of MLVs with OPM or covalent anchoring with PAM.
- Characterization of MLVs for size, shape, lamellarity, entrapment efficiency, and ligand density.
- In vivo biodistribution studies in albino rats, including serum stability assessments.
- Inhibition studies using pre-injection of hydrolyzed mannan to confirm receptor-mediated uptake.
Main Results:
- Liposomal Amp B showed significantly higher accumulation in macrophage-rich organs (liver, spleen, lungs) compared to free Amp B.
- Ligand anchoring further increased the rate and extent of drug accumulation.
- Macrophagic uptake of ligand-anchored liposomes was inhibited by hydrolyzed mannan, indicating receptor-mediated uptake.
- PAM-linked liposomes demonstrated higher hepato-splenic accumulation.
- OPM-coated liposomes showed preferential accumulation in the lungs.
Conclusions:
- Mannopyranoside is a specific ligand for targeting bioactives to liver and spleen macrophages.
- OPM preferentially targets bioactives to alveolar macrophages in the lungs.
- Ligand-anchored liposomes offer a promising strategy for targeted delivery of amphotericin B to specific macrophage populations.