In vivo fate of large unilamellar sphingomyelin-cholesterol liposomes after intraperitoneal and intravenous injection into rats

doi:10.1016/0304-4165(81)90341-X

Biochimica et Biophysica Acta (BBA) - General Subjects

Volume 674, Issue 1, 17 April 1981, Pages 10-18

https://doi.org/10.1016/0304-4165(81)90341-X Get rights and content

Abstract

We investigated the fate of intraperitoneally and intravenously injected reverse phase evaporation vesicles of fairly uniform size (100–200 m) with respect to blood celarance, tissue distribution and integrity in vivo. The vesicles are composed of sphingomyelin and cholesterol in a molar ratio 3 : 2 and contain ¹²⁵I-labeled poly(vinyl pyrrolidone) in the aqueous compartment. It is shown that following an intrapersoneal injection the vesicles are transported intact, and not associated with cells, from the peritoneal activity to the blood and are subsequently taken up mainly by liver and spleen, where, particularly in liver, the phospholipid is partially metabolized. After an intraperitoneal injection the rate of vesicle-uptake by liver and spleen is reduced by a factor of 2–3 compared to the rate of vesicle-uptake by liver and spleen following an intravenous injection. The peritoneal cavity functions as a reservior of vesicles for some hours. The rates of blood clearance and uptake of the vesicles by liver and spleen appear to be slower than that found for vesicles of different lipid composition.

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In mammals, the lymphatic absorption and drainage routes of the peritoneal cavity have been widely studied, which could form a specialized system transporting fluid from the peritoneal cavity to the blood circulation system [29,30]. It has been reported in rats that the intraperitoneally injected liposomes-vesicles are transported from the peritoneal activity to the blood and are subsequently taken up mainly by liver and spleen [31]. In teleost fish, there is lack of diaphragm and lymph nodes, however, several studies reported that some antigens like vitellogenin and colloidal carbon could be readily transported from the peritoneal cavity into the blood and then transported into other lymphoid tissues with blood circulation [32,33].
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One of the functions of macrophages is to provide a defense mechanism against tumor cells. In the last decades the mechanism of tumor cell killing by macrophages have been studied extensively. The tumor cytotoxic function of macrophages requires stimulation either with bacterial cell wall products such as lipopolysaccharide (LPS) or muramyldipeptide (MDP) or with cytokines such as interferon-γ (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Activated macrophages secrete several substances that are directly involved in tumor cell killing i.e. tumor necrosis factor (TNF) and nitric oxide (NO). On the other hand, substances are secreted that are able to stimulate tumor cell growth, depending on the stage and the nature of the tumor. Several clinical trials have been performed aiming at the activation of macrophages or dendritic cells, a subpopulation of the macrophages. In this review we will summarize and discuss experimental studies and clinical trials based on the activation of macrophages.
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Gadolinium-incorporating lipid-nanoemulsions (Gd-nanoLE) for neutron-capture therapy were prepared. As a more convenient administration route than the intraperitoneal (i.p.) injection previously reported, the intravenous (i.v.) injections in tumor-bearing hamsters were carried out at an administration volume of 1 ml, which was the maximum tolerable injection volume of an i.v. injection and half that of an i.p. injection. When the standard-Gd-nanoLE of 1.5 mg Gd/ml was administered, the absolute bioavailability in the i.p. injection was 57%, probably resulting from incomplete absorption from the peritoneal cavity into the blood stream. The biodistribution data revealed that the i.v. injection had three advantages over the i.p. injection, namely, a faster and higher accumulation of Gd-nano LE, and a more extended retention time in the tumor. Two i.v. injections of the standard-Gd-nanoLE with a 24 h interval doubled the tumor accumulation of Gd, resulting in 49.7 μg Gd/g wet tumor 12 h after administration. By using a twofold Gd-enriched formulation (High-Gd-nanoLE) of 3.0 mg Gd/ml in the repeated administration schedule, the accumulation was doubled again, reaching 101 μg Gd/g wet tumor. This level was comparable to the maximum level in the single i.p. injection previously reported. These results demonstrated that i.v. injection could be an alternative to i.p. injection as an administration route.
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In vivo fate of large unilamellar sphingomyelin-cholesterol liposomes after intraperitoneal and intravenous injection into rats

Abstract

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Biochem. Biophys. Res. Commun.

Biochim. Biophys. Acta

Methods Enzymol.

J. Lipid Res.

FEBS Lett.

Biochim. Biophys. Acta

Biochem. Biophys. Res. Commun.

Biochim. Biophys. Acta

Cancer Res.

Cancer Res.

Cancer Res.

Cancer Res.