Self-assembled Supramolecular Nanomicelles from Bile Acid-Docetaxel Conjugate are Highly Tolerable with Improved Therapeutic Efficacy

2021 ◽  
Author(s):  
Vedagopuram Sreekanth ◽  
Sanjay Pal ◽  
Sandeep Kumar ◽  
Varsha Komalla ◽  
Poonam Yadav ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Bile Acid ◽  
Therapeutic Efficacy ◽  
Lithocholic Acid ◽  
Self Assembled

Herein, we present the engineering of a supramolecular nanomicellar system that is composed of self-assembled units of PEGylated lithocholic acid (LCA)-Docetaxel (DTX) conjugate (LCA-DTX-PEG). We tethered a short polyethylene glycol...

Pharmacological effects of secondary bile acid microparticles in diabetic murine model

2020 ◽  
Vol 16 ◽  
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Bozica Kovacevic ◽  
Corina Mihaela Ionescu ◽  
Giuseppe Luna ◽  
...  
Keyword(s):  
Bile Acid ◽  
Blood Glucose ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Diabetes Treatment ◽  
Secondary Bile Acid ◽  
Glucose Levels ◽  
Anti Inflammatory ◽  
Antidiabetic Effects

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent anti-inflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA nanoparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.

Fecal Microbiome and Bile Acid Metabolome in Adult Short Bowel Syndrome

2021 ◽  
Author(s):  
Harold J. Boutte ◽  
Jacqueline Chen ◽  
Todd N. Wylie ◽  
Kristine M. Wylie ◽  
Yan Xie ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Short Bowel Syndrome ◽  
Lithocholic Acid ◽  
Intestinal Failure ◽  
Patient Specific ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Fecal Microbiome ◽  
Short Bowel

Background & Aims: Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to two years to determine which patients will wean from PN. Here we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Methods: Stool and sera were collected from healthy controls and from SBS patients (n=52) with ileostomy, jejunostomy, ileocolonic and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS, and serum amino acid analyses. Results: SBS patients exhibited altered gut microbiota with reduced gut microbial diversity compared to healthy controls. We observed differences in the microbiomes of SBS patients with ileostomy vs. jejunostomy, jejunocolonic vs. ileocolonic anastomoses, and PN-dependence compared to those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in SBS patients, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic acid. Conclusions: Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select SBS patients, promoting the ability to wean from PN. Pro-adaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.

scholarly journals Pre-existing anti-polyethylene glycol antibody reduces the therapeutic efficacy and pharmacokinetics of PEGylated liposomes

Theranostics ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 3164-3175 ◽  
Author(s):  
Yuan-Chin Hsieh ◽  
Hsin-Ell Wang ◽  
Wen-Wei Lin ◽  
Steve R. Roffler ◽  
Ta-Chun Cheng ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Therapeutic Efficacy ◽  
Pegylated Liposomes

scholarly journals Effects of clofibrate on some microsomal hydroxylations involved in the formation and metabolism of bile acids in rat liver

1976 ◽  
Vol 156 (2) ◽  
pp. 445-448 ◽  
Author(s):  
B O Angelin ◽  
I Björkhem ◽  
K Einarsson
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Rat Liver ◽  
Lithocholic Acid ◽  
Present Knowledge ◽  
Acid Formation ◽  
Microsomal Metabolism ◽  
Endogenous Cholesterol

1. The liver microsomal metabolism of [4-14C]cholesterol, endogenous cholesterol, 7 α-hydroxy-4-[6 β-3H]cholesten-3-one, 5-β-[7 β-3H]cholestane-3 α, 7 α-diol and [3H]lithocholic acid was studdied in control and clofibrate (ethyl p-chlorophenoxyisobutyrate)-treated rats. 2. The extent of 7 α-hydroxylation of exogenous [414C]cholesterol and endogenous cholesterol, the latter determined with a mass fragmentographic technique, was the same in the two groups of rats. The extent of 12 α-hydroxylation of 7 α-hydroxy-4-cholesten-3-one and 5 β-cholestane-3 α, 7 α-diol was increased by about 60 and 120% respectively by clofibrate treatment. The 26-hydroxylation of 5 β-cholestane-3 α, 7 α-diol was not significantly affected by clofibrate. The 6 β-hydroxylation of lithocholic acid was about 80% higher in the clofibrate-treated animals than in the controls. 3. The results are discussed in the context of present knowledge about the liver microsomal hydroxylating system and bile acid formation in patients with hypercholesterolaemia, treated with clofibrate.

scholarly journals Defective FXR-FGF15 signaling and bile acid homeostasis in cystic fibrosis mice can be restored by the laxative polyethylene glycol

2019 ◽  
Vol 316 (3) ◽  
pp. G404-G411 ◽  
Author(s):  
Anna Bertolini ◽  
Ivo P. van de Peppel ◽  
Marcela Doktorova-Demmin ◽  
Frank A. J. A. Bodewes ◽  
Hugo de Jonge ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Polyethylene Glycol ◽  
Bile Acid ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Farnesoid X Receptor ◽  
Fibroblast Growth ◽  
Gastrointestinal Complications ◽  
Osmotic Laxative

The gastrointestinal phenotype of cystic fibrosis (CF) features intestinal bile acid (BA) malabsorption, impaired intestinal farnesoid X receptor (FXR) activation, and consequently reduced fibroblast growth factor 19 (FGF19, FGF15 in mice) production. The osmotic laxative polyethylene glycol (PEG) has been shown to decrease intestinal mucus accumulation in CF mice and could, by doing so, improve BA reabsorption. Here we determined the effect of PEG on BA excretion and FXR-FGF15 signaling in CF mice. Male Cftr−/−tm1Unc (CF) and wild-type (WT) littermates were administered PEG 4000 in drinking water and fed either chow or a semisynthetic diet. PEG was withdrawn for 3 days before termination. Fecal BA excretion was measured at PEG dosages of 37 g/l (100%) and 0 g/l (0%). Ileal FXR activation was assessed by gene expression of its downstream targets Fgf15 and small heterodimer partner ( Shp). In CF mice, PEG withdrawal increased fecal BA excretion on either diet compared with full PEG dosage (chow, 2-fold, P = 0.06; semisynthetic, 4.4-fold, P = 0.007). PEG withdrawal did not affect fecal BA excretion in WT mice on either diet. After PEG withdrawal, gene expression levels of intestinal FXR target genes Fgf15 and Shp were decreased in CF mice but unaffected in WT littermates. PEG did not affect the gene expression of the main intestinal BA transporter apical sodium-dependent bile acid transporter (ASBT). PEG treatment ameliorates intestinal BA malabsorption in CF mice and restores intestinal FXR-FGF15 signaling, independent from Asbt gene expression. These findings highlight the potential of PEG in the prevention and treatment of the gastrointestinal phenotype of CF. NEW & NOTEWORTHY A gastrointestinal feature of cystic fibrosis is bile acid malabsorption and consequent impairment of farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling. FXR-FGF15 signaling regulates various metabolic processes and could be implicated in metabolic and gastrointestinal complications of cystic fibrosis, such as diabetes and liver disease. In cystic fibrosis mice, treatment with the osmotic laxative polyethylene glycol is associated with decreased fecal bile acid loss and restoration of FXR-FGF15 signaling.

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