Fx-5A peptide complex (Fx-5A), a High Density Lipoproteins (HDL) mimetic, has been shown to reduce atherosclerosis. The safety and toxicokinetics of Fx-5A administered IV by 30 min infusion at 8, 25 or 75 mg/kg body weight or vehicle, once every other day for 27 days, were assessed in cynomolgus monkeys. The Fx-5A was well tolerated at all doses. At the highest dose, there were statistically significant effects on hematology and clinical chemistry parameters that were considered non-adverse. Dose-dependent recoverable non-adverse erythrocytes morphological changes (acanthocytes, echinocytes, spherocytes, microcytes, and/or schistocytes) were observed. Fx-5A was not hemolytic in in-vitro fresh NHP or human blood assay. There were no Fx-5A-related statistically significant changes for any cardiovascular function, ECG or respiratory parameters, when compared to control. In addition, there were no Fx-5A-related effects on organ weights, macroscopic or microscopic endpoints. Finally, Fx-5A exhibited sporadic non-appreciable detection of anti-Fx-5A antibodies and a dose-dependent linear toxicokinetics with T value ranges from 2.7 to 6.2 h. In conclusion, the No Observed Adverse Effect Level was considered to be 75 mg/kg/day with associated exposures average C and AUC of 453 μg/mL and 2232 h μg/mL, respectively, on Day 27.
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http://dx.doi.org/10.1016/j.yrtph.2018.10.009 | DOI Listing |
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Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, China.
Mol Pharm
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Department of Pharmaceutics and Brain Barriers Research Center, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States.
J Pers Med
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Division of Cardiology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University Hospital Paolo Giaccone, University of Palermo, 90127 Palermo, Italy.
High-density lipoprotein (HDL) cholesterol is traditionally viewed as protective against cardiovascular disease (CVD). However, emerging evidence reveals that dysfunctional HDL, characterized by impaired reverse cholesterol transport (RCT), reduced anti-inflammatory and antioxidant activities and increased endothelial dysfunction, which can contribute to coronary artery disease (CAD). Dysfunctional HDL, resulting from oxidative modifications of Apolipoprotein A-1 (Apo A-1) and enzyme inactivation, fails to effectively remove cholesterol from peripheral tissues and may promote inflammation and atherosclerosis.
View Article and Find Full Text PDFInt J Mol Sci
July 2024
Lipoprotein Drug Delivery Research Laboratory, Department of Microbiology, Immunology & Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Cytotoxic activity has been reported for the xanthone α-mangostin (AMN) against Glioblastoma multiforme (GBM), an aggressive malignant brain cancer with a poor prognosis. Recognizing that AMN's high degree of hydrophobicity is likely to limit its systemic administration, we formulated AMN using reconstituted high-density lipoprotein (rHDL) nanoparticles. The photophysical characteristics of the formulation, including fluorescence lifetime and steady-state anisotropy, indicated that AMN was successfully incorporated into the rHDL nanoparticles.
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Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010 Graz, Styria, Austria; BioTechMed-Graz, Mozartgasse 12/II, 8010 Graz, Styria, Austria. Electronic address:
Low levels of high-density lipoprotein (HDL) and impaired HDL functionality have been consistently associated with increased susceptibility to infection and its serious consequences. This has been attributed to the critical role of HDL in maintaining cellular lipid homeostasis, which is essential for the proper functioning of immune and structural cells. HDL, a multifunctional particle, exerts pleiotropic effects in host defense against pathogens.
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