Chronic liposome administration in mice: effects on reticuloendothelial function and tissue distribution

Area of Science:

• Pharmacology and Toxicology
• Nanomedicine
• Immunology

Background:

• Liposomes are frequently utilized drug delivery systems with a known tendency to accumulate in the reticuloendothelial (RE) system.
• Understanding the long-term effects of liposome administration on host defense mechanisms is crucial for optimizing therapeutic strategies.

Purpose of the Study:

• To investigate the impact of chronic, low-to-moderate dose liposome administration on drug metabolism, RE system phagocytic function, and organ size in mice.
• To evaluate how liposome characteristics (size, composition, lipid peroxides) and dosing regimens affect RE system blockade and tissue distribution of encapsulated drugs.

Main Methods:

• Chronic intravenous administration of varying liposome formulations to mice.
• Assessment of pentobarbital metabolism rates.
• Measurement of RE phagocytic index.
• Determination of spleen and liver sizes.
• Quantification of tissue distribution of liposome-entrapped [14C]sucrose.

Main Results:

• Chronic liposome dosing had minimal impact on pentobarbital metabolism, except for sphingomyelin liposomes at high doses.
• RE phagocytic function impairment correlated with liposome size, composition, dose frequency, and presence of lipid peroxides.
• Sphingomyelin liposomes caused the most significant RE blockade, followed by distearoylphosphatidylcholine-cholesterol, and then egg phosphatidylcholine-cholesterol liposomes.
• Liposomes with vitamin E showed slightly less RE function impairment.
• RE blockade led to decreased liver and increased spleen uptake of liposome contents, with no significant uptake in non-RE tissues.

Conclusions:

• Chronic liposome administration can modulate RE system function, with effects dependent on liposome properties and dosing.
• Sphingomyelin-containing liposomes are most effective at inducing RE blockade.
• Strategies aiming to increase non-RE tissue uptake by inducing RE blockade with empty liposomes may not be successful.
• Liver to spleen ratios of entrapped substances offer a sensitive measure of RE blockade.