We report a case that involves the use of intravenous lipid emulsion as an antidote for a drug overdose involving a 20-month-old girl who had ingested a potentially lethal amount of the tricyclic antidepressant (TCA) dothiepin. The patient's condition continued to deteriorate despite implementation of standard pediatric treatment recommendations for TCA toxicity. Administration of intravenous lipid emulsion in addition to standard therapy (including sodium bicarbonate) and direct-current cardioversion for ventricular arrhythmia led to a successful outcome. The case report is followed by a review of the current evidence underlying this novel therapy and the background on its use. TCA toxicity is addressed specifically.
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http://dx.doi.org/10.1542/peds.2011-0867 | DOI Listing |
Angew Chem Int Ed Engl
January 2025
University of Science and Technology of China School of Biomedical Engineering, Department of Polymer Science and Engineering, 96 Jinzhai Road, 230026, Hefei, CHINA.
Lipid nanoparticles (LNPs) based messenger RNA (mRNA) therapeutics hold immense promise for treating a wide array of diseases, while their nonhepatic organs targeting and insufficient endosomal escape efficiency remain challenges. For LNPs, polyethylene glycol (PEG) lipids have a crucial role in stabilizing them in aqueous medium, but they severely hinder cellular uptake and reduce transfection efficiency. In this study, we designed ultrasound (US)-assisted fluorinated PEGylated LNPs (F-LNPs) to enhance spleen-targeted mRNA delivery and transfection.
View Article and Find Full Text PDFActa Biomater
January 2025
College of Chemistry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, PR China. Electronic address:
mRNA-based protein replacement therapy has become one of the most widely applied forms of mRNA therapy, with lipid nanoparticles (LNPs) being extensively studied as efficient delivery platforms for mRNA. However, existing LNPs tend to accumulate in the liver or kidneys after intravenous injection, highlighting the need to develop vectors capable of targeting specific organs. In this study, we synthesized a small library of ionizable lipids and identified PPz-2R as a promising candidate, exhibiting lung-targeting capabilities, high mRNA transfection efficiency, and good stability through structure-activity relationship studies.
View Article and Find Full Text PDFBiomaterials
January 2025
144 College St, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada. Electronic address:
The development of disease-modifying therapeutics for Alzheimer's disease remains challenging due to the complex pathology and the presence of the blood-brain barrier. Previously we have described the investigation of a brain-penetrating multifunctional bioreactive nanoparticle system capable of remodeling the hypoxic and inflammatory brain microenvironment and reducing beta-amyloid plaques improving cognitive function in a mouse model of Alzheimer's disease. Despite the linkage of hypoxia and inflammation to metabolic alteration, the effects of this system on modulating cerebral glucose metabolism, mitochondrial activity and synaptic function remained to be elucidated.
View Article and Find Full Text PDFDrug Deliv Transl Res
January 2025
Center for Coronary Heart Disease, Department of Cardiology, National Center for Cardiovascular Diseases of China, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Rd, Beijing, 100037, China.
Atherosclerosis is one of the leading causes of ischemic cardiovascular disease worldwide. Recent studies indicated that vascular smooth muscle cells (VSMCs) play an indispensable role in the progression of atherosclerosis. Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated promising clinical applications in the treatment of atherosclerosis.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
March 2025
Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA.
Lipid nanoparticles (LNPs) are often liver tropic, presenting challenges for LNP-delivered mRNA therapeutics intended for other tissues, as off-target expression in the liver may increase side effects and modulate immune responses. To avoid off-target expression in the liver, miR-122 binding sites have been used by others in viral and non-viral therapeutics. Here, we use a luciferase reporter system to compare different copy numbers and insertion locations of miR-122 binding sequences to restrict liver expression.
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