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

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Summary

Introduction

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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