Cytotoxic effect induced by retinoic acid loaded into galactosyl-sphingosine containing liposomes on human hepatoma cell lines

Díaz, Cecilia; Vargas, Ernesto Martínez; Gätjens-Boniche, Omar

doi:10.1016/j.ijpharm.2006.06.034

Cited by 34 publications

(16 citation statements)

References 32 publications

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“…These results suggested stronger cytotoxic activity of DTX NE in comparison to both marketed formulation Taxotere and free drug (DTX), which in turn indicate less drug is required for cytotoxic action in NE formulations. Current findings are in agreement with previously reported NEs, liposomes and nanoparticles, advocating higher cytotoxic effect of these delivery systems than the conventional systems (Díaz et al, 2006;Choudhury et al, 2014).…”

Section: Cell Uptake and Cytotoxicitysupporting

confidence: 93%

Perspectives of nanoemulsion assisted oral delivery of docetaxel for improved chemotherapy of cancer

et al. 2014

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Context: Nanoemulsions (NE) are one of the robust delivery tools for drugs due to their higher stability and efficacy. Objectives: The purpose of present investigation is to develop stable, effective and safe NE of docetaxel (DTX). Methods: Soybean oil, lecithin, Pluronic F68, PEG 4000 and ethanol were employed as excipients and NEs were prepared by hot homogenization followed by ultra-sonication. NEs were optimized and investigated for different in vitro and in vivo parameters viz. droplet size, poly dispersity index, charge; zeta potential, drug content and in vitro drug release, in vitro cytotoxicity, in vitro cell uptake and acute toxicity. Transmission electron microscopy was performed to study morphology and structure of NEs. Stability studies of the optimized formulation were performed. Results: Droplet size, poly dispersity index, zeta potential, drug content and in vitro drug release were found to be 233.23 ± 4.3 nm, 0.24 ± 0.010, À43.66 ± 1.9 mV, 96.76 ± 1.5%, 96.25 ± 2.1%, respectively. NE F11 exhibited higher cell uptake (2.83 times than control) and strong cytotoxic activity against MCF-7 cancer cells (IC 50 ; 13.55 ± 0.21 mg/mL at 72 h) whereas no toxicity or necrosis was observed with liver and kidney tissues of mice at a dose of 20 mg/kg. Transmission electron microscopy ensured formation of poly-dispersed and spherical droplets in nanometer range. NE F11 (values indicated above) was selected as the optimized formulation based on the aforesaid parameters. Conclusion: Conclusively, stable, effective and safe NE was developed which might be used as an alternative DTX therapy.

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Section: Cell Uptake and Cytotoxicitysupporting

confidence: 93%

Perspectives of nanoemulsion assisted oral delivery of docetaxel for improved chemotherapy of cancer

et al. 2014

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“…It is known that ASGPR is highly expressed in the human hepatoma cell lines HepG2 and Hep3B (22,31,32), and in agreement, biotinylated asialofetuin showed high level binding in these cells (Fig. 1A), indicating that asialofetuin had been biotinylated and the biotinylated asialofetuin could interact with ASGPR.…”

Section: Specific Labeling Of Hcc Cells With Biotinylated Asialofetuinsupporting

confidence: 73%

“…The positivity was significantly associated with the existence of HCC (P ¼ 0.023) and the existence of portal vein tumor thrombus (P ¼ 0.039), but not with tumor size, differentiation status, or the disease extent as classified by the TNM classification or the Milan criteria. Discussion ASGPR is abundantly and exclusively expressed on the surface of hepatocytes and HCC cells (31)(32)(33). Hep Par 1 is a human hepatocyte-specific antibody, which recognizes antigens localized in mitochondria and has been used to identify liver-derived cells including normal hepatocytes and HCC cells (35).…”

Section: Detection Of Afp Mrnamentioning

confidence: 99%

Isolation of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Using a Novel Cell Separation Strategy

Cao²,

Chen³

et al. 2011

Clinical Cancer Research

143

139

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Purpose: To establish a sensitive and specific isolation and enumeration system for circulating tumor cells (CTC) in patients with hepatocellular carcinoma (HCC).Experimental Design: HCC cells were bound by biotinylated asialofetuin, a ligand of asialoglycoprotein receptor, and subsequently magnetically labeled by antibiotin antibody-coated magnetic beads, followed by magnetic separation. Isolated HCC cells were identified by immunofluorescence staining using Hep Par 1 antibody. The system was used to detect CTCs in 5 mL blood. Blood samples spiked with Hep3B cells (ranging from 10 to 810 cells) were used to determine recovery and sensitivity. Prevalence of CTCs was examined in samples from HCC patients, healthy volunteers, and patients with benign liver diseases or non-HCC cancers. CTC samples were also analyzed by FISH.Results: The average recovery was 61% or more at each spiking level. No healthy, benign liver disease or non-HCC cancer subjects had CTCs detected. CTCs were identified in 69 of 85 (81%) HCC patients, with an average of 19 AE 24 CTCs per 5 mL. Both the positivity rate and the number of CTCs were significantly correlated with tumor size, portal vein tumor thrombus, differentiation status, and the disease extent as classified by the TNM (tumor-node-metastasis) classification and the Milan criteria. HER-2 gene amplification and TP53 gene deletion were detected in CTCs.Conclusion: Our system provides a new tool allowing for highly sensitive and specific detection and genetic analysis of CTCs in HCC patients. It is likely clinically useful in diagnosis and monitoring of HCC and may have a role in clinical decision making.

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“…These data are in agreement with previous studies concerning the noncytotoxic nature of the carrier (PC) and loaded flavonoids. 62,63 The microscopic images of HepaRG cells treated with higher concentration (200 µg/mL) of flavonosomes were shown in Figure 8C and D. The images support the obtained cytotoxicity results, whereby after 24 hours treatment with the various formulated flavonosomes revealed no signs of toxicity, which was confirmed by the absence of intracytoplasmic vesicles formation as reported in previous studies; 31,64,65 in contrast, the flavonosome treated HepaRG cells inclusive of both hepatocyte-like cells (H) and epithelium-like cells (I) remain healthy and intact similar to the morphology and architecture of untreated control cells (Figure 8C and D). This strongly suggests that flavonosomes could play an effective hepatosupplemental/hepatoprotective role.…”

mentioning

confidence: 99%

Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique

Karthivashan¹,

Kura²,

Abas³

et al. 2016

IJN

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This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as “flavonosome”. Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA–phosphatidylcholine) through four different methods of synthesis – bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug–carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA–phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of −39.07±3.55 mV, and the entrapment efficiency was >98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert >85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate.

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Cytotoxic effect induced by retinoic acid loaded into galactosyl-sphingosine containing liposomes on human hepatoma cell lines

Cited by 34 publications

References 32 publications

Perspectives of nanoemulsion assisted oral delivery of docetaxel for improved chemotherapy of cancer

Perspectives of nanoemulsion assisted oral delivery of docetaxel for improved chemotherapy of cancer

Isolation of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Using a Novel Cell Separation Strategy

Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique

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