Different intrahepatic distribution of phosphatidylglycerol and phosphatidylserine liposomes in the rat

Abstract

thelial cells. Liver endothelial cells have numerous pores (feLiposomes with diameters of 200 to 400 nm containing nestrae), with an average diameter of 150 nm. 1 Larger bloodphosphatidylserine (PS) or phosphatidylglycerol (PG) were borne particles are therefore supposed to be prevented from injected intravenously into rats. Two hours after injection, contact with the hepatocytes situated across the endothelial 75% of the injected dose of PS liposomes was found in the lining. liver and only 10% found in the spleen, while 35% of the PG In a previous study 2 we found that the hepatic uptake of liposomes was found in the liver and as much as 40% was 200-nm liposomes (ie, phosphatidylcholine (PC), cholesterol found in the spleen. Cell-isolation experiments revealed the (chol), and phosphatidylserine (PS) in a 4:5:1 molar ratio) following remarkable difference in the intrahepatic distribuwas virtually unaffected in rats that were depleted of their tion between the two liposome formulations: the PS liposomesKupffer cells by pretreatment with liposomal doxorubicin. distributed in about equal amounts to Kupffer cells and hepaCell-isolation experiments showed that the liposomes were tocytes, despite their size (200-400 nm) exceeding that of mainly found to be associated with the hepatocyte populathe endothelial fenestrae (average 150 nm), whereas the PG tion. Transmission electron microscopy revealed that the enliposomes were only taken up by the Kupffer cells and not dothelial lining was damaged due to treatment with doxoruat all by the hepatocytes. Double-label studies, using lipobicin, which, thus, could explain the uptake of liposomes by somes in which the lipid-moiety was radio labeled with hepatocytes. Surprisingly, however, we also found that al- 423.) AnimalsHepatic uptake of conventional multilamellar liposomes Specific pathogen-free female Wistar or male Wag/Rij rats (Harlarger than 150 nm in diameter has so far been attributed to lan CPB, Zeist, The Netherlands), weighing between 200 and 250 phagocytosis by Kupffer cells. Kupffer cells are situated in g, were used in all experiments. The animals received care in accorthe liver sinusoids, which are lined by a single layer of endo-dance with the institution's guidelines.

Therapeutic Efficacy of Liposomal Rifabutin in a Mycobacterium avium Model of Infection

“…However, different in vivo behaviors have been reported. PI inhibits uptake by the MPS and prolongs the circulation times of liposomes (2,16,30), while liposomes with PS or PG are rapidly cleared from the circulation (7,9). These data, together with the good values for the incorporation parameters obtained in the present work, led to the selection of a lipid mixture that contained PC and PS (7:3).…”

“…However, after the establishment of the infection, both organs remain infected. The greater reduction in the level of infection observed in livers may be due to the fact that liposomes that contain PS are preferentially targeted to the liver (7). On the other hand, the prophylactic administration of liposomes resulted in a greater reductions in the bacterial loads in the spleen.…”

“…According to the literature, liposomes that contain PS or PG administered intravenously are rapidly cleared from the circulation, mainly due to their uptake by the resident macrophages of the liver and spleen (7,9). On the other hand, MPS uptake of liposomes that contain PI is inhibited and the circulation of the liposomes in the bloodstream is prolonged (2,16).…”

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

“…In fact, it is believed that most liposomes internalized by the liver are localized to Kupffer cells, regardless of their size (Litzinger et al, 1994). In contrast, liposomes prepared from phosphatidylserine with a size between 200 and 400 nm were found in both hepatic parenchymal cells and Kupffer cells in almost equal amounts, despite being larger than the endothelial fenestrae pore size (Daemen et al, 1997). Moreover, Awasthi et al (2003) have reported that small and large liposomes (136.2 and 318.0 nm, respectively) were taken up more readily by the liver than liposomes that were 165.5-275.0 nm in size.…”

Nebulized Amphotericin B Combined with Intravenous Amphotericin B in Rats with Severe Invasive Pulmonary Aspergillosis

“…1). Colloidal gold-labeled liposomes were prepared as described previously by Daemen et al (4). The lipid film consisted of the same lipids as the liposomal membrane of liposomal AMB in the same molar ratio (2:1:0.8 hydrogenated soy phosphatidyl choline/distearoyl phosphatidyl glycerol/cholesterol).…”