scholarly journals A Polyethylenimine-Linoleic Acid Conjugate for Antisense Oligonucleotide Delivery

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jing Xie ◽  
Lesheng Teng ◽  
Zhaogang Yang ◽  
Chenguang Zhou ◽  
Yang Liu ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Ribonucleotide Reductase ◽  
Antisense Oligonucleotide ◽  
Cellular Internalization ◽  
Protein Levels ◽  
Gel Retardation Assay ◽  
Promising Agent ◽  
Acid Conjugate ◽  
Oligonucleotide Delivery ◽  
Specific Inhibitors

A novel antisense oligonucleotide (ASO) carrier, polyethylenimine conjugated to linoleic acid (PEI-LA), was synthesized and evaluated for delivery of LOR-2501 to tumor cells. LOR-2501 is an ASO targeting ribonucleotide reductase R1 subunit (RRM1). In this study, PEI-LA was synthesized by reacting PEI (Mw ~ 800) with linoleoyl chloride. Gel retardation assay showed complete complexation between PEI-LA and LOR-2501 at N/P ratio above 8. No significant cytotoxicity was observed with these complexes at the tested dosage levels. Interestingly, at N/P ratio of >6, levels of cellular uptake of PEI-LA/LOR-2501 were double that of PEI/LOR-2501 complexes of the same N/P ratio. PEI-LA/LOR-2501 induced downregulation of 64% and 70% of RRM1 at mRNA and protein levels, respectively. The highest transfection activity was shown by PEI-LA/LOR-2501 complexes at N/P ratio of 10. Finally, using pathway specific inhibitors, clathrin-mediated endocytosis was shown to be the principle mechanism of cellular internalization of these complexes. In conclusion, PEI-LA is a promising agent for the delivery of ASOs and warrants further investigation.

Conjugated Linoleic Acid Causes a Marked Increase in Liver α-Tocopherol and Liver α-Tocopherol Transfer Protein in C57BL/6 J Mice

2010 ◽  
Vol 80 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Pei-Min Chao ◽  
Wan-Hsuan Chen ◽  
Chun-Huei Liao ◽  
Huey-Mei Shaw
Keyword(s):  
Antioxidant Enzymes ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Thiobarbituric Acid ◽  
Control Group ◽  
Thiobarbituric Acid Reactive Substances ◽  
Control Groups ◽  
Protein Levels ◽  
Transfer Protein ◽  
And Control

Conjugated linoleic acid (CLA) is a collective term for the positional and geometric isomers of a conjugated diene of linoleic acid (C18:2, n-6). The aims of the present study were to evaluate whether levels of hepatic α-tocopherol, α-tocopherol transfer protein (α-TTP), and antioxidant enzymes in mice were affected by a CLA-supplemented diet. C57BL/6 J mice were divided into the CLA and control groups, which were fed, respectively, a 5 % fat diet with or without 1 g/100 g of CLA (1:1 mixture of cis-9, trans-11 and trans-10, cis-12) for four weeks. α-Tocopherol levels in plasma and liver were significantly higher in the CLA group than in the control group. Liver α-TTP levels were also significantly increased in the CLA group, the α-TTP/β-actin ratio being 2.5-fold higher than that in control mice (p<0.01). Thiobarbituric acid-reactive substances were significantly decreased in the CLA group (p<0.01). There were no significant differences between the two groups in levels of three antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). The accumulation of liver α-tocopherol seen with the CLA diet can be attributed to the antioxidant potential of CLA and the ability of α-TTP induction. The lack of changes in antioxidant enzyme protein levels and the reduced lipid peroxidation in the liver of CLA mice are due to α-tocopherol accumulation.

Targeted Lipid Nanoparticles for Antisense Oligonucleotide Delivery

2014 ◽  
Vol 15 (9) ◽  
pp. 847-855 ◽  
Author(s):  
Raquel Petrilli ◽  
Josimar Eloy ◽  
Juliana Marchetti ◽  
Renata Lopez ◽  
Robert Lee
Keyword(s):  
Antisense Oligonucleotide ◽  
Lipid Nanoparticles ◽  
Oligonucleotide Delivery

scholarly journals Ethylcellulose nanoparticles as a new “in vitro” transfection tool for antisense oligonucleotide delivery

2020 ◽  
Vol 229 ◽  
pp. 115451 ◽  
Author(s):  
S. Leitner ◽  
S. Grijalvo ◽  
C. Solans ◽  
R. Eritja ◽  
M.J. García-Celma ◽  
...  
Keyword(s):  
Antisense Oligonucleotide ◽  
Oligonucleotide Delivery ◽  
In Vitro Transfection

Therapeutic efficacy of lipid emulsions of docetaxel-linoleic acid conjugate in breast cancer

2018 ◽  
Vol 546 (1-2) ◽  
pp. 61-69 ◽  
Author(s):  
Tao Zhang ◽  
Meng Li ◽  
Ruyi Yang ◽  
Dong Zhang ◽  
Jibin Guan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Linoleic Acid ◽  
Therapeutic Efficacy ◽  
Lipid Emulsions ◽  
Acid Conjugate

scholarly journals URI-1 Levels Are Elevated in Fatty Livers of db/db and C57BL/6 Mice Fed Trans-10, Cis-12 Conjugated Linoleic Acid

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 383-383
Author(s):  
Luis Cordero-Monroy ◽  
Carla Taylor ◽  
Peter Zahradka
Keyword(s):  
Body Weight ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Fatty Liver ◽  
Western Blotting ◽  
Weight Ratio ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Body Weight Ratio ◽  
Protein Levels

Abstract Objectives This study was designed to investigate whether unconventional prefoldin RPB5 interactor (URI)-1 mediates hepatic accumulation of triglyceride (TG) in response to a diet with trans-10,cis-12 conjugated linoleic acid (t10,c12 CLA) in lean or genetically obese mice. URI-1 belongs to the prefoldin family of proteins that have been shown to coordinate nutrient availablility by transcriptional regulation of genes involved in glucose and lipid metabolism. Thus, it was hypothesized that URI-1 in liver is involved in increased fatty acid uptake and accumulation leading to fatty liver. Methods C57BL/6 and db/db mice were randomly assigned to two diet groups, control (CTL) and t10,c12 CLA (0.4% w/w). After 4 weeks, the mice were weighed and euthanized. Livers were dissected, weighed and stored at –80°C. Liver lysates were prepared from the tissue for Western blotting to measure hepatic protein levels of URI-1 and FABP1. The amount of lipid in the livers was determined using the LabAssay™ Triglyceride kit, a colorimetric TG assay. Results The liver to body weight ratio of db/db and C57BL/6 mice fed t10,c12 CLA increased by 90% and 52%, respectively, compared to their counterparts fed the CTL diet. Likewise, the hepatic TG concentration (mg TG/mg protein) was increased 38% and 5-fold, respectively, in CLA-fed db/db and C57BL/6 mice compared to CTL db/db and C57BL/6 mice. Western blotting showed that FABP1 levels were approximately 2-fold greater in the db/db t10,c12 CLA group relative to the db/db CTL group, and may contribute to increased fatty acid uptake. Furthermore, URI-1 protein levels were elevated 4-fold in db/db and C57BL6 mice fed t10,c12 CLA compared to their respective CTL groups. Lastly, correlation analysis revealed that URI-1 levels were significantly correlated with hepatic TG concentrations (r = 0.61) and liver/body weight ratio (r = 0.64). Conclusions This study revealed a relationship between hepatic TG accumulation and URI-1, a protein associated with hepatocellular carcinoma (HCC) and cirrhosis. This study provides a basis for in vitro experiments exploring the causative role of URI-1 in propagating hepatic TG accumulation, and ultimately the progression of fatty liver disease to HCC and cirrhosis. Funding Sources University Collaborative Research Project, NSERC Discovery, and University of Manitoba Graduate Enhancement of Tri-Council Stipends.

scholarly journals Enhanced Oral Bioavailability, Anti-Tumor Activity and Hepatoprotective Effect of 6-Shogaol Loaded in a Type of Novel Micelles of Polyethylene Glycol and Linoleic Acid Conjugate

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 107 ◽  
Author(s):  
Huiyun Zhang ◽  
Qilong Wang ◽  
Congyong Sun ◽  
Yuan Zhu ◽  
Qiuxuan Yang ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Oral Bioavailability ◽  
Water Solubility ◽  
Oral Absorption ◽  
Treatment Effectiveness ◽  
Hepatoprotective Effect ◽  
Nanoprecipitation Method ◽  
Acid Conjugate

：6-shogaol is a promising anti-cancer and anti-inflammatory agent. However, the treatment effectiveness of 6-shogaol is limited by poor water solubility, poor oral absorption and rapid metabolism. Herein, 6-shogaol loaded in micelles (SMs) were designed to improve 6-shogaol’s solubility and bioavailability. The micelles of a PEG derivative of linoleic acid (mPEG2k-LA) were prepared by the nanoprecipitation method with a particle size of 76.8 nm, and entrapment of 81.6 %. Intriguingly, SMs showed a slower release in phosphate buffer saline (PBS) (pH = 7.4) compared to free 6-shogaol while its oral bioavailability increased by 3.2–fold in vivo. More importantly, the in vitro cytotoxic effect in HepG2 cells of SMs was significantly higher than free 6-shogaol. Furthermore, SMs could significantly improve the tissue distribution of 6-shogaol, especially liver and brain. Finally, SMs showed a better hepatoprotective effect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo than free 6-shogaol. These results suggest that the novel micelles could potentiate the activities of 6-shogaol in cancer treatment and hepatoprotection.

scholarly journals A Covalently Stabilized Lipid−Polycation−DNA (sLPD) Vector for Antisense Oligonucleotide Delivery

2011 ◽  
Vol 8 (3) ◽  
pp. 709-715 ◽  
Author(s):  
Xiaojuan Yang ◽  
Yong Peng ◽  
Bo Yu ◽  
Jianhua Yu ◽  
Chenguang Zhou ◽  
...  
Keyword(s):  
Antisense Oligonucleotide ◽  
Oligonucleotide Delivery
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