What question did this study set out to answer?

To determine how liposome surface charge, reticuloendothelial system blockade, and protein cross-linking affect the plasma clearance, hepatic uptake, and enzymatic catabolism of liposome-entrapped proteins.

August 1, 1974European Journal of Biochemistry

Control of the Rate of Hepatic Uptake and Catabolism of Liposome‐Entrapped Proteins Injected into Rats. Possible Therapeutic Applications

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Authors

GGGregory GregoriadisUniversity of London DNDiane NeerunjunAstraZeneca (United Kingdom)

Discussion

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Implication

Animal study demonstrates charge-dependent hepatic uptake and catabolism of liposome-entrapped proteins in rats, indicating methods to optimize liposomal drug delivery.

Key Points

To determine how liposome surface charge, reticuloendothelial system blockade, and protein cross-linking affect the plasma clearance, hepatic uptake, and enzymatic catabolism of liposome-entrapped proteins.
Entrapped radiolabeled albumin and β-fructofuranosidase into liposomes prepared from phosphatidylcholine, cholesterol, and charged lipids in a 7:2:1 molar ratio.
Injected charged or neutral liposomes into rats and evaluated clearance kinetics, uptake competition between charges, and the effect of reticuloendothelial blockade via carbon administration.
Assessed the effect of chemical cross-linking of liposomal protein cargo on resistance to degradation by hepatic lysosomal enzymes.
Plasma removal exhibited biphasic kinetics where rapid-phase clearance and hepatic uptake were highest for negatively charged liposomes, intermediate for neutral liposomes, and lowest for positively charged liposomes, before transitioning to a uniform slow phase across all charges.
Co-administration of excess positively charged liposomes attenuated the rapid phase of negatively charged liposomes, while carbon blockade increased hepatic localization during the rapid phase, indicating shared uptake sites and dual involvement of Kupffer and parenchymal cells.
Cross-linking liposome-entrapped albumin and β-fructofuranosidase enhanced protein stability and reduced catabolic degradation by liver lysosomal enzymes.

Cite This Study

Gregoriadis et al. (1974) studied this question.

synapsesocial.com/papers/6a887a7c6308d976f48b2c4e https://doi.org/10.1111/j.1432-1033.1974.tb03681.x

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Implication

Animal study demonstrates charge-dependent hepatic uptake and catabolism of liposome-entrapped proteins in rats, indicating methods to optimize liposomal drug delivery.

Control of the Rate of Hepatic Uptake and Catabolism of Liposome‐Entrapped Proteins Injected into Rats. Possible Therapeutic Applications

Discussion

Member takes

Implication

Key Points

Cite This Study

Control of the Rate of Hepatic Uptake and Catabolism of Liposome‐Entrapped Proteins Injected into Rats. Possible Therapeutic Applications

Discussion

Member takes

Implication

Key Points

Cite This Study

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