Kinetic modeling of liposome degradation in blood circulation

Abstract

The aim of this study is to develop a kinetic model for the quantitative evaluation of, and to examine dose dependency in liposome degradation in blood circulation in vivo. Multilamellar liposomes labeled with 3H-inulin were administered intravenously into rats and the time courses of blood concentration and urinary excretion of 3H-inulin were measured. The dosages of liposomes were fixed at 1, 5, and 100 mumolPCkg-1. Remarkable saturation was found in the time courses of both blood concentration and urinary excretion. Then a kinetic model for the degradation of liposomes in blood was developed, assuming that the degradation follows the first order rate process for each dose. The model fitted the observed time courses of excreted 3H-inulin well, and dose dependency could be observed in the rate constants for liposome degradation, which are more sensitive than urinary excretion of 3H-inulin. The degradation rate constant correlated well with the uptake rate constant, which suggests the same underlying mechanism for both uptake and degradation. These results indicate the usefulness of kinetic modeling in the quantitative evaluation of liposome degradation in blood circulation in vivo.

A Novel Method to Radiolabel Stealth Liposome through 1,2- dimyristoyl-sn-glycero-3-phosphoethanolamine-N-DTPA with 99mTc and Biological Evaluation

“…The observed renal elimination may be explained by the fact that liposomes are metabolized in the body and the radionuclide remains bound to small fragments of lipid that may be filtered at the glomerulus. We explored this hypothesis, and our results did not find labeled liposomes in urine being in accordance with previous reports [26].…”

Insights into accelerated liposomal release of topotecan in plasma monitored by a non-invasive fluorescence spectroscopic method

“…di- and tri-methylamine) are also present at levels which vary from patient to patient [48–50]. Other effects have been suggested to account for variability of liposomal release kinetics in plasma such as destabilization of the bilayer due to protein interactions [5, 7, 40, 42, 51, 52]. However, these theories could not explain the effects seen here as release kinetics obtained in plasma would have been significantly different from release kinetics obtained in studies performed in an ultrafiltrate of the same plasma (which was not the case).…”

Design rules for nanomedical engineering: from physical virology to the applications of virus-based materials in medicine

“…• Metallic nanoparticles have physiochemical properties that make them useful for imaging and therapeutic applications, but some formulations show slow tissue clearance [5]. • Polymers and liposomes are biodegradable and nontoxic, but are prone to degradation in vivo [6,7]. Their large size (>100 nm) also hinders tissue penetration and effective distribution [1].…”

“…sketch of the experimental set-up comprising a syringe pump (1); a syringe with particles in solution (2); inlet Silastic tubing (3); a parallel plate flow chamber (4), outlet Silastic tubing (5); a microscope (6) with a digital camera(7) connected to a computer (8) for storage and imaging analysis. Reproduced with permission from Gentile at al.…”