Liver Targeting Liposomes Containing .BETA.-Sitosterol Glucoside with Regard to Penetration-Enhancing Effect on HepG2 Cells.

Kawano, Keiichi; Nakamura, Kouji; Hayashi, Kyoko; Nagai, Tsuneji; Takayama, K.; Maitani, Yoshie

doi:10.1248/bpb.25.766

Cited by 11 publications

(7 citation statements)

References 23 publications

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“…In relation to this point, the literature shows that phytosterol glucosides and cholesterol glucoside can arise from various sources including diet (Ly et al 2007). For example, soy products containing phytosterols and phytosterol glucosides are major components of the human diet for some populations (Sugiyama and Seki 1991;Kawano et al 2002;Maitani et al 1995;Shimizu et al 1997). A second potential source is by autosynthesis in which human cells may make sterol glucosides if the substrates of sterols and glucose are present.…”

Section: Discussionmentioning

confidence: 99%

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

Tabata

Wilson

et al. 2008

Neuromol Med

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Epidemiological studies of the Guamanian variants of amyotrophic lateral sclerosis (ALS) and parkinsonism, amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC), have shown a positive correlation between consumption of washed cycad seed flour and disease occurrence. Previous in vivo studies by our group have shown that the same seed flour induces ALS and PDC phenotypes in out bred adult male mice. In vitro studies using isolated cycad compounds have also demonstrated that several of these are neurotoxic, specifically, a number of water insoluble phytosterol glucosides of which β-sitosterol β-D-glucoside (BSSG) forms the largest fraction. BSSG is neurotoxic to motor neurons and other neuronal populations in culture. The present study shows that an in vitro hybrid motor neuron (NSC-34) culture treated with BSSG undergoes a dose-dependent cell loss. Surviving cells show increased expression of HSP70, decreased cytosolic heavy neurofilament expression, and have various morphological abnormalities. CD-1 mice fed mouse NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript chow pellets containing BSSG for 15 weeks showed motor deficits and motor neuron loss in the lumbar and thoracic spinal cord, along with decreased glutamate transporter labelling, and increased glial fibrillary acid protein reactivity. Other pathological outcomes included increased caspase-3 labelling in the striatum and decreased tyrosine-hydroxylase labelling in the striatum and substantia nigra. C57BL/6 mice fed BSSG-treated pellets for 10 weeks exhibited progressive loss of motor neurons in the lumbar spinal cord that continued to worsen even after the BSSG exposure ended. These results provide further support implicating sterol glucosides as one potential causal factor in the motor neuron pathology previously associated with cycad consumption and ALS-PDC.

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Section: Discussionmentioning

confidence: 99%

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

Tabata

Wilson

et al. 2008

Neuromol Med

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“…Binding of Sit-G to HepG2 cell was seen to increase proportionately with the number of cells added. This reaction was higher than that of human cervical carcinoma HeLa cells, indicating that Sit-G had interacted with hepatocytes [81]. Another specific interaction of SG-liposomes with hepatocyte may be related to their affinity with glucose transporters.…”

Section: Mechanism Of Sg-ligands For Liver-targeting Of Hepg2 Cellsmentioning

confidence: 83%

“…Incorporation of Sit-G increased the association of FD-4 in HepG2 cells. This effect was related to the increase in Sit-G concentration and incubation time, as compared with control [81].…”

Section: Mechanism Of Sg-ligands For Liver-targeting Of Hepg2 Cellsmentioning

confidence: 83%

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Application of Sterylglucoside-Containing Particles for Drug Delivery

Maitani¹,

Nakamura²,

Kawano

2005

CPB

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Recent advances in biotechnology have promoted biomolecular targeting of drugs, peptides and genes in the treatment and management of major diseases and infections. Therapeutic development of drugs and delivery systems may have various objectives: Systemic drugs require optimal delivery and uptake at target sites; peptide drugs require alternative routes of administration, such as nasal or intestinal absorption; gene medicines need to be delivered efficiently, safely and selectively to diseased areas. The propensity of ligand-modified liposomes to carry drugs and genes to desirable sites has been extensively examined and current reports show considerable progress in this field. Sterylglucoside (SG) is a novel absorption-enhancer of peptide drugs across nasal and intestinal mucosae. Physico-chemical properties and biodistribution of liposomes incorporating SG were studied and compared against the profiles of aglycon and sitosterol derivatives of SG. It was shown that SG particles aided colon drug delivery and increased bioavailability of peptide drugs after nasal and intestinal administration. In addition, they were able to enhance anticancer effects in liver cancer chemotherapy. Biological fate and interaction of SG with hepatocytes support the novel proposition of liver-targeting SG-liposomes.

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“…We evaluated the toxicity and efficacy of the delivery of liposomes formulated with various cationic lipids and then selected the DMTAP liposomes for further use. SG, derived from Hibiscus manihot, is known to accumulate in the liver, especially in hepatocytes (Kawano et al, 2002). Hence for the purpose of liver targeting, SG was conjugated with the liposomes to deliver the siRNA to the asialoglycoprotein receptors (ASGPR) in the hepatocytes.…”

Section: Introductionmentioning

confidence: 99%

Suppression of hepatitis B virus-derived human hepatocellular carcinoma by NF-κB-inducing kinase-specific siRNA using liver-targeting liposomes

et al. 2009

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Hepatitis B virus triggers an increase of NF-kappaB inducing kinase (NIK)-dependent NF-kappaB activation, followed by the promotion of hepatocellular carcinoma (HCC). Here, we examined the inhibitory effect of NIK-specific siRNA on NF-kappaB signaling and HCC. The results of this study indicated that these siRNAs suppressed HBV-derived HCC by regulating NIK activation. To exert a protective effect from degradation enzyme, cationic liposomes were contrived and modified to contain beta-sitosterol glucoside to target the asialoglycoprotein receptors in liver cancer cells. The cationic dimyristoyl diacyltrimethylammonium propane liposomes were prepared by a reverse-phase evaporation method with slight modification. beta-Sitosterol glucoside was added to the lipid mixture at the beginning of the liposome preparation for the purpose of liver targeting. These liposomes assisted the delivery of the siRNA to specific cells and protected it from various lyases, followed by the ultimate suppression of HCC.

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Liver Targeting Liposomes Containing .BETA.-Sitosterol Glucoside with Regard to Penetration-Enhancing Effect on HepG2 Cells.

Cited by 11 publications

References 23 publications

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

Application of Sterylglucoside-Containing Particles for Drug Delivery

Suppression of hepatitis B virus-derived human hepatocellular carcinoma by NF-κB-inducing kinase-specific siRNA using liver-targeting liposomes

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