Abstract
BackgroundNanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research.ObjectivesFour kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were prepared and their in vitro and in vivo safety were evaluated and compared.MethodsIn vitro nanotoxicity evaluations included assessments of cell morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and membrane fluidity. An umbilical vein cell line (Eahy.926) and a kind of macrophages (J774.A1) were used as cell models considering that intravenous route is dominant for micelle delivery systems. In vivo analyses included complete blood count, lymphocyte subset analysis, detection of plasma inflammatory factors and histological observations of major organs after intravenous administration to KM mice.ResultsAll the micelles enhanced inflammatory molecules in J774.A1 cells, likely resulting from the increased ROS levels. PEG-PG-PCL and PEEP-PCL micelles were found to increase the J774.A1 cell volume. This likely correlated with the size of PEG-PG-PCL micelles and the polyphosphoester structure in PEEP-PCL. PEG-DSPE micelles inhibited the growth of Eahy.926 cells via inducing apoptosis. This might relate to the structure of DSPE, which is a type of phospholipid and has good affinity with cell membrane. No evidence was found for cell membrane changes after treatment with these micelles for 24 h. In the in vivo study, during 8 days of 4 time injection, each of the four nanocarriers altered the hematic phase differently without changes in inflammatory factors or pathological changes in target organs.ConclusionsThese results demonstrate that the micelles investigated exhibit diverse nanotoxicity correlated with their structures, their biosafety is different in different cell model, and there is no in vitro and in vivo correlation found. We believe that this study will certainly provide more scientific understandings on the nanotoxicity of amphiphilic polymeric micelles.
Highlights
Nanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research
These results demonstrate that the micelles investigated exhibit diverse nanotoxicity correlated with their structures, their biosafety is different in different cell model, and there is no in vitro and in vivo correlation found
We believe that this study will certainly provide more scientific understandings on the nanotoxicity of amphiphilic polymeric micelles
Summary
Nanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research. In medical and pharmaceutical fields, nanomaterials are packaged into different nanocarriers for biosensing, magnetic resonance imaging, optical detection, and drug delivery systems, among others [2,3,4,5,6,7,8]. Many in vitro and in vivo studies have recently been conducted to demonstrate that nanomaterials in direct contact with cell surfaces may lead to several types of damages. In a study of Yen et al, an increase in the size of the macrophages and a decreasing in cell population were observed after treatment with Au and Ag nanoparticles at ≥10 ppm [9]. Some toxicological in vitro studies have reported that nanomaterials can influence reactive oxygen species (ROS) formation [10]. Certain studies have investigated further influences of nanomaterials on inflammatory factors or protein/gene expression of cells. Yen et al determined that Au nanoparticles (especially those of a smaller diameter) could upregulate the expression of the proinflammatory genes interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
