Purpose: Gallic acid (GA) is a polyphenolic compound with proven efficacy against hepatic fibrosis in experimental animals. However, it suffers from poor bioavailability and rapid clearance that hinders its clinical investigation. Accordingly, we designed and optimized reverse micelle-loaded lipid nanocapsules (RMLNC) using Box-Behnken design that can deliver GA directly into activated-hepatic stellate cells (aHSCs) aiming to suppress hepatic fibrosis progression.
Methods: GA-RMLNC was prepared using soft energy, solvent free phase inversion temperature method. Effects of formulation variables on particle size, zeta potential, entrapment efficiency (EE%) and GA release were studied. In-vivo biodistribution of GA-RMLNC in rats and in-vitro activities on aHSCs were also explored.
Results: Nano-sized GA-RMLNCs (30.35 ± 2.34 nm) were formulated with high GA-EE% (63.95 ± 2.98% w/w) and physical stability (9 months). The formulated system showed burst GA release in the first 2 h followed by sustained release profile. In-vivo biodistribution imaging revealed that RMLNC-loaded with rhodamine-B accumulated mainly in rats' livers. Relative to GA; GA-RMLNC displayed higher anti-proliferative activities, effective internalization into aHSCs, marked down-regulation in pro-fibrogenic biomarkers' expressions and elevated HSCs' apoptosis.
Conclusions: These findings emphasize the promising application of RMLNC as a delivery system in hepatic fibrosis treatment, where successful delivery of GA into aHSCs was ensured via increased cellular uptake and antifibrotic activities.
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http://dx.doi.org/10.1007/s11095-020-02891-z | DOI Listing |
Expert Opin Drug Saf
December 2024
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Introduction: The risk of HCC is twice as high in diabetic patients compared to non-diabetic ones, suggesting that diabetes advances carcinogenesis in the liver through a variety of mechanisms. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve liver outcomes, emerging as promising agents to treat hepatocellular carcinoma (HCC) in patients with type 2 diabetes mellitus (T2DM).
Methods: We searched PubMed and Scopus databases for articles presenting an association between SGLT2is and HCC to explore the putative mechanisms of action underlying the anti-proliferative activity of SGLT2is.
Clin J Gastroenterol
December 2024
Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
We report the case of a 70-year-old woman with advanced hepatic encephalopathy (HE) secondary to metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis who exhibited an excellent response to portosystemic shunt embolization. Four years earlier, she was diagnosed as having MASH-related cirrhosis accompanied by multiple mesenteric vein-inferior vena cava shunts. As her condition progressed, she suffered recurrent HE that was unresponsive to oral medication, prompting the decision to proceed with shunt embolization.
View Article and Find Full Text PDFAdv Ther
December 2024
Professor Emeritus, Tohoku University, Sendai, Japan.
Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia, which is characterised by progressive worsening of dyspnoea and lung function. Nintedanib treatment is recommended to slow IPF disease progression. The aim of this post-marketing surveillance (PMS) study was to evaluate the safety and effectiveness of nintedanib over 24 months in patients with IPF in a real-world setting in Japan.
View Article and Find Full Text PDFDaru
December 2024
Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, POB 11795, Egypt.
Background: Bile salts enriched nanovesicles (bilosomes) have been attention worthy in the past few years due to their distinctive effect on the enhancement of drug delivery through various physiological administration routes. Oral delivery of multifunctioning phytochemical curcumin has faced a lot of difficulties due to its scarce solubility and poor oral bioavailability.
Objective: The current investigation aimed to develop curcumin loaded bilosomes for improvement of oral curcumin bioavailability with maximum efficiency and safety.
iScience
December 2024
Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children's Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Increasing evidence points toward vitamin D (VD) having lipometabolism and immune-related properties to protect against related metabolic diseases through influencing DNA methylation with inconsistent results. Simultaneously, its relatively precise molecular metabolism on the progression of metabolic-associated fatty liver disease (MAFLD) remains uncertain. Here, we report an unprecedented role and possible mechanism for VD supplementation on the alleviation of high-fat diet (HFD)-induced MAFLD.
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