Guanfu base A·HCl (GFA·HCl) solution, approved by the China Food and Drug Administration (CFDA) in 2005, has been used in the treatment of arrhythmia. However, the poor targeting and absorption of GFA·HCl have severely affected its clinical application. In this study, a nanolipid-based, Guanfu base A (GFA) delivery system was designed to improve the deficiency of GFA·HCl and realize better clinical effect. The GFA-loaded solid nanolipids (GFASN) with a core/shell structure, composed of Poloxamer 188, lecithin, and medium-chain fatty acid, were prepared using a high-pressure homogenate emulsification method. Results showed that GFASN possessed well morphology and stability during the process of lyophilization and rehydration at 220-260 nm. Safety evaluation revealed that ear vein injection of GFASN (14 mg/kg) were safe enough and of good biocompatibility. More importantly, GFASN can better alleviate the arrhythmia of rats, especially in ventricular ectopia and ventricular tachycardia, than GFA·HCl solution. Pharmacokinetic behaviors and targeting evaluation in mice demonstrated that nanolipids can help GFA achieve longer circulation time in blood and better heart specificity. Collectively, these promising findings suggested that this kind of nanolipids was an ideal delivery carrier for GFA in the treatment of cardiovascular disease.
Microplastics (MPs) are plastic particles of a diameter of less than 5 mm and a major carrier of pollution. In accordance with its diameter range, MPs can be divided into microplastics (100–5 mm) and nanoplastics (<100 nm). In recent years, in addition to the impact of MPs on the environment, the ways in which MPs affect the body has also attracted continuous attention. However, relevant studies on the cytotoxicity of MPs are not comprehensive. Based on the current research, this paper summarizes four main cytotoxic mechanisms of MPs, inducing oxidative stress, damaging cell membrane organelles, inducing immune response, and genotoxicity. Generally, MPs cause cytotoxicity such as oxidative stress, damage to cell membranes and organelles, activation of immune responses, and genotoxicity through mechanical damage or induction of cells to produce reactive oxygen species. Understanding these toxic mechanisms is helpful for the evaluation and prevention of human toxicity of MPs. This paper also analyzes the limitations of current research and prospects for future research into cellular MPs, with the aim of providing a scientific basis and reference for further research into the toxic mechanism of MPs.
Microplastics (MPs) have become increasingly serious global problems due to their wide distribution and complicated impacts on living organisms. To obtain a comprehensive overview of the latest research progress on MPs, we conducted a bibliometric analysis combined with a literature review. The results showed that the number of studies on MPs has grown exponentially since 2010. Recently, the hotspot on MPs has shifted to terrestrial ecosystems and biological health risks, including human health risks. In addition, the toxic effects, identification and quantification of MPs are relatively new research hotspots. We subsequently provide a review of MPs studies related to health risks to terrestrial higher mammals and, in particular, to humans, including detection methods and potential toxicities based on current studies. Currently, MPs have been found existing in human feces, blood, colon, placenta and lung, but it is still unclear whether this is associated with related systemic diseases. In vivo and in vitro studies have demonstrated that MPs cause intestinal toxicity, metabolic disruption, reproductive toxicity, neurotoxicity, immunotoxicity through oxidative stress, apoptosis and specific pathways, etc. Notably, in terms of combined effects with pollutants and neurotoxicity, the effects of MPs are still controversial. Future attention should be paid to the detection and quantification of MPs in human tissues, exploring the combined effects and related mechanisms of MPs with other pollutants and clarifying the association between MPs and the development of pre-existing diseases. Our work enhances further understanding of the potential health risks of MPs to terrestrial higher mammals.
Graphical abstract
Supplementary Information
The online version contains supplementary material available at 10.1007/s10653-022-01458-8.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.