Abstract
Liver sinusoidal endothelial cells (LSECs) possess fenestrae whose number can be increased both in vitro and in situ by depolymerizing the actin cytoskeleton [1]. Specially designed liposomes can be targeted with a high efficiency to LSECs. These liposomes, which were surface grafted with poly-anionized albumin (Aco-HSA) [2], can be filled with various substances, such as microfilament-disrupting drugs. This technique opens up attractive possibilities to modulate the liver sieve of LSECs with liposome-encapsulated microfilament-disrupting drugs in vivo. The goal of this study was to alter the sieve's porosity by using cytochalasin B-loaded Aco-HSA liposomes. The increase in the liver sieve porosity induced by cytochalasin B (CB) may be exploited therapeutically to improve the extraction of atherogenic lipoproteins from the circulation; or to enhance the efficiency of liposome-mediated gene or drug delivery to hepatocytes.
Highlights
Liver sinusoidal endothelial cells (LSECs) possess fenestrae whose number can be increased both in vitro and in situ by depolymerizing the actin cytoskeleton [1]
filamentous actin (F-actin) staining showed a weak dissolution of cytoplasmic F-actin when cultured LSECs were incubated with 0.025 microgram/ml free cytochalasin B (CB) (Fig. 1A)
SsFFLtlSiuragEeoiunCsrisresnesfgticbr1oeenfarcLtseSd-ECawnsidtwhsci0tah.0nrn2hi5nogmdeaiclmercointgrero-apnmhma/mlilcolriCdoigBnrafsophrhosw2oshfoacuulorltssus(rAoedf) Fluorescence- and scanning electron micrographs of cultured LSECs treated with 0.025 microgram/ml CB for 2 hours (A) Staining of LSECs with rhodamine-phalloidin shows a loss of stress fibers
Summary
Liver sinusoidal endothelial cells (LSECs) possess fenestrae whose number can be increased both in vitro and in situ by depolymerizing the actin cytoskeleton [1]. Designed liposomes can be targeted with a high efficiency to LSECs. Specially designed liposomes can be targeted with a high efficiency to LSECs These liposomes, which were surface grafted with poly-anionized albumin (Aco-HSA) [2], can be filled with various substances, such as microfilamentdisrupting drugs. This technique opens up attractive possibilities to modulate the liver sieve of LSECs with liposome-encapsulated microfilament-disrupting drugs in vivo. The increase in the liver sieve porosity induced by cytochalasin B (CB) may be exploited therapeutically to improve the extraction of atherogenic lipoproteins from the circulation; or to enhance the efficiency of liposome-mediated gene or drug delivery to hepatocytes
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