Hepatic toxicity assessment of cationic liposome exposure in healthy and chronic alcohol fed mice

Abstract

The utilisation of nanoparticles as the means of targeted delivery of therapeutics and/or imaging agents could greatly enhance the specific transport of biologically active payloads to target tissues while avoiding or reducing undesired side-effects. To allow for this to become a reality, the question of potential toxicological effects needs to be addressed. In the present investigation, a cationic liposome with prospective for medical applications was constructed and thoroughly assessed for any material-induced hepatic adverse effects in vivo − in healthy and alcoholic hepatic disease models and in vitro − (HepG2 cells). The data demonstrated that intravenous injection of liposomes did not cause any significant in vivo hepatic toxicity (inflammation, alterations in blood parameters, anti-oxidant depletion, acute phase response and histopathology) at doses of 200 μg per mouse in either healthy or chronically alcohol fed mice. Additionally, the in vitro material-induced adverse effects (cytotoxicity, inflammation or albumin secretion) were all also minimal. The data from this study demonstrated that the intravenous injection of cationic liposomes does not cause hepatic toxicity. This investigation is important as it investigates the toxicity of a nano-sized material in a model of alcoholic hepatic disease in vitro and in vivo. This is an area of research in the field of nanotoxicology that is currently almost entirely overlooked.

A Flow Cytometry‐based Method for the Screening of Nanomaterial‐induced Reactive Oxygen Species Production in Leukocytes Subpopulations in Whole Blood

“…As a side note, it should be stated that the liposome-related data in this study fit very well with a previous investigation in which a comprehensive in vitro analysis found that potential adverse effects after exposure of endothelial cells and macrophages to liposomes did not induce a cytotoxic or inflammatory response in any of the experimental conditions [36]. In addition, the same liposomes were also shown to be highly biocompatible after intravenous exposure of C57BL/6 mice [42]. This is the first study of its kind in which liposome association by the three main leukocyte subpopulations in human blood is quantified.…”

Smart nanocarrier-based drug delivery systems for cancer therapy and toxicity studies: A review

“…The surface charge of nanocarriers is another challenge to SDDS design, as the surface charge largely determines the interaction between the body and nanocarriers. Nanocarriers with positive charges, or cationic nanocarriers, show greater toxicity compared to ones with negative surface charges [214] , [288] . A shell around the nanocarriers plays a vital role in reducing the toxicity of nanocarriers.…”

Highly efficient siRNA transfection in macrophages using apoptotic body-mimic Ca-PS lipopolyplex

“…[2][3][4][5][6][7][8][9][10] However, mainstream cationic transfection agents are associated with several drawbacks such as lipid-induced cytotoxicity and non-applicability in hard-to-transfect cells. [11][12][13][14][15][16][17][18] Among these hard-to-transfect cells, macrophages are notoriously difficult to transfect using liposomes and, therefore, are usually genetically manipulated using viral vectors; but, preparation of these viral vectors could be challenging and presents biosafety threats to researchers. 19 Macrophages are a type of immune cells specialized in engulfing hazardous biological entities, eg, dead cells, pathogens, cancer cells, bacteria etc.…”