The cellular toxicities of surfactants, a solvent, and an antifreeze that are included in herbicide formulations were assessed by measuring their effects on membrane integrity, metabolic activity, mitochondrial activity, and total protein synthesis rate in a cell culture. Polyethylene glycol, propylene glycol, and monoethylene glycol exhibited no cellular toxicity even at a high concentration of 100 mM. Sodium lauryl ether sulfate and polyoxyethylene lauryl ether significantly damaged the membrane, disturbed cellular metabolic activity, and decreased mitochondrial activity and the protein synthesis rate; however, their toxicity was far below those of the severely toxic chemicals at comparable concentrations. The severely toxic category included polyoxypropylene glycol block copolymer, polyoxyethylene tallow amine, and polyoxyethylene lauryl amine ether. These surfactants were cytotoxic between 3.125 microM and 100 microM in a dose-dependent manner. However, the toxicity graph of concentration vs toxicity had a point of inflection at 25 microM. The slope of the toxicity graph was gentle when the concentration was below 25 microM and steep when the concentration was greater than 25 microM. In conclusion, our results suggest that the toxicity of surfactants be taken care of pertinent treatment of acute herbicide intoxication.
Animals ; Cell Line ; Cell Membrane/drug effects ; Herbicides/*chemistry ; Mice ; Mitochondria/drug effects ; Polyethylene Glycols/toxicity ; Sodium Dodecyl Sulfate/toxicity ; Surface-Active Agents/chemistry/*toxicity ; Toxicity Tests

Acetylcysteine ; pharmacology ; Antioxidants ; pharmacology ; Composite Resins ; toxicity ; Dental Materials ; toxicity ; Fibroblasts ; drug effects ; metabolism ; Gingiva ; cytology ; drug effects ; Humans ; Methacrylates ; toxicity ; Polyethylene Glycols ; toxicity ; Polymethacrylic Acids ; toxicity ; Polymethyl Methacrylate ; toxicity ; Reactive Oxygen Species ; metabolism ; Resins, Synthetic ; toxicity

We investigated whether glyphosate influences the cellular toxicity of the surfactants TN-20 and LN-10 on the mouse fibroblast-like cells, alveolar epithelial cells, and a heart cell line. The cytotoxicity of TN-20 and LN-10 (0.4-100 microM), in the presence or absence of glyphosate was determined by assessing membrane integrity. TN-20 toxicity was significantly lower in the presence of 50 microM glyphosate for the fibroblast-like cell (6.25 microM; 3.9% +/- 3.4% vs -4.8% +/- 0.7%), for the alveolar cells (0.78 microM; 5.7% +/- 0.9% vs 0.1% +/- 0.6%), and for the heart cell line (25.0 microM; 7.9% +/- 3.0% vs 19.4% +/- 0.7%) compared to that of TN-20 alone. The cellular toxicity of LN-10 towards the fibroblast-like cells was found to be increased in the presence of 50 microM glyphosate when LN-10 concentrations of 50 microM (31.3% +/- 3.9% vs 19.2% +/- 0.9%) and 100 microM (62.1% +/- 3.4% vs 39.0% +/- 0.7%) were compared to that of LN-10 alone. These results suggest that the mixture toxicity may be a factor in glyphosate-surfactant toxicity in patients with acute glyphosate herbicide intoxication.
Animals ; Cell Line ; Cell Survival/drug effects ; Glycine/*analogs & derivatives/chemistry/toxicity ; Herbicides/chemistry/*toxicity ; Mice ; Polyethylene Glycols/*chemistry ; Surface-Active Agents/*chemistry

Polymyxin E shows effective treatment of the infection induced by resistant gramnegative bacteria, but its nephrotoxicity severely limits the clinical application of this drug. In this work, methoxypolyethylene glycols 2000 (mPEG2K)-polymyxin E (PME) was synthesized via chemical grafting reaction and had been characterized. The antimicrobial activity and cytotoxicity of mPEG2K-PME in vitro were investigated on Escherichia coli and HK-2 cells, separately. Intra-abdominal infection model was further established in order to study the therapeutic effect and the toxic effect on kidney of mice. The results showed that mPEG2K-PME exhibited significant inhibitory effect on Escherichia coli and had a lower toxicity on HK-2 cells in vitro. At the same time, mPEG2K-PME had a good efficacy in the treatment of Escherichia coli infected mice in vivo. Moreover, nephrotoxicity caused by mPEG2K-PME was significantly reduced compared to free PME. mPEG2K-PME is promising in development of new preparations with high efficiency and low toxicity.
Animals ; Cell Line ; Colistin ; pharmacology ; toxicity ; Escherichia coli ; drug effects ; Escherichia coli Infections ; drug therapy ; Humans ; Kidney ; cytology ; drug effects ; Mice ; Polyethylene Glycols ; chemistry

Two kinds of gel materials were prepared from silk fibroin with polyepoxy compound at subfreezing temperature and higher temperature. In order to evaluate the feasibility of their application in biomaterials, we tested the cytotoxicity of silk fibroin gels by detecting the effect of the extracted liquid on the cell relative proliferation rate of L-929 mouse fibroblasts. The results indicated that both of the gel materials displayed high relative proliferation rate and grade 1 cytotoxicity, being in the allowed range of medical application. The cytotoxicity tests on polyepoxy compound and glutaraldehyde were conducted too, and the cytotoxicity of polyepoxy compound was obviously lower than that of glutaraldehyde. Polyepoxy compound can be used as a more safe cross-link reagent for silk fibroin modification.
Animals ; Biocompatible Materials ; chemistry ; Bombyx ; chemistry ; Cross-Linking Reagents ; chemistry ; Fibroblasts ; drug effects ; Fibroins ; chemistry ; Gels ; chemical synthesis ; toxicity ; Mice ; Polyethylene Glycols ; chemistry ; Temperature

Chitosan and its derivatives are extensively studied as non-viral gene delivery vectors nowadays. Polyethylene glycol-chitosan (mPEG-CS) copolymers were synthesized by oxidation of mPEG-OH and then combined mPEG-CHO with amino groups on chitosan chains. The in vitro cytotoxicity of copolymers was evaluated by MTT method. The results showed > 70% cell viability of HeLa and A549 cells after incubation with mPEG-CS copolymer from concentration 5 to 100 microg x mL(-1). The mPEG-CS copolymers with various degrees of PEG substitution were combined with DNA and the properties of mPEG-CS/DNA complexes were investigated such as nanoparticle size, zeta potential and agarose gel analysis. The best one among all these mPEG-CS copolymers was mPEG (3.55) -CS, for its capability to condense plasmid DNA was most efficient. For this reason, mPEG (3.55) -CS was picked out to mediate plasmid enhanced green fluorescence protein (pEGFP) and transfect HeLa and A549 cells. The expression of green fluorescence protein was observed by fluorescence microscope and the transfection efficiency was detected by flow cytometry. The gene expression mediated by mPEG-CS was resistant to serum, and the optimal transfection efficiency (8.1% for HeLa cells and 4.8% for A549 cells) of mPEG-CS/EGFP system was obtained under the condition of N/P 40 and 48 h transfection time. These results indicate that mPEG-CS copolymer is an efficient non-viral gene vector.
Adenocarcinoma ; pathology ; Cell Line, Tumor ; Chitosan ; chemistry ; toxicity ; Drug Carriers ; Genetic Vectors ; chemistry ; HeLa Cells ; Humans ; Lung Neoplasms ; pathology ; Nanoparticles ; Particle Size ; Plasmids ; Polyethylene Glycols ; chemistry ; toxicity ; Polymers ; Transfection

The therapeutic application of deoxypodophyllotoxin (DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers (mPEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles (DPT-PM) were about (20 ± 2.84)% and (98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10 mol·L, which showed significant difference from free DPT (P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.
Antineoplastic Agents ; chemistry ; toxicity ; Cell Survival ; drug effects ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Drug Design ; HeLa Cells ; Humans ; Micelles ; Particle Size ; Podophyllotoxin ; analogs & derivatives ; chemistry ; toxicity ; Polyesters ; chemistry ; Polyethylene Glycols ; chemistry ; Solubility ; Surface Properties

This is a study on the biodegradable polymers as gene controlled-released coatings for gene transfer. The PELA (poly (Dl-lactic acid)-co-poly (ethylene glycol), and PLGAE (poly (lactic acid)-co-poly (ethylene glycol)-co-poly (glycolic acid) random copolymer) were synthesized and prepared as the coatings of plasmid pCH110 in the transfection. All kinds of factors affecting the loading efficiency, cytotoxicity, transfection efficiency and the course of the degradation and release in vitro were discussed. The average diameters of microspheres of PELA and PLGAE were 1-3 microm and 0.72 microm respectively. The loading efficiency levels of them were 62% and 70% respectively. The transfection efficiency levels of two kinds of pCH110 delivery system for COS-1 cells were higher and two of them had few cytotoxicity. After transfection, the X-gal assay was performed and reported positive for 96 h. The biodegradable polymeric materials as gene carriers possess their potential superiority.
Biocompatible Materials ; DNA ; chemistry ; Drug Carriers ; chemical synthesis ; chemistry ; toxicity ; Gene Transfer Techniques ; Lactates ; chemical synthesis ; chemistry ; toxicity ; Lactic Acid ; chemical synthesis ; chemistry ; toxicity ; Polyethylene Glycols ; chemical synthesis ; chemistry ; toxicity ; Polyglycolic Acid ; chemical synthesis ; chemistry ; toxicity ; Polymers ; chemical synthesis ; chemistry ; toxicity ; Transfection

The aim of this study is to prepare self-microemulsifying drug delivery system (SMEDDS) of the mixture of paeonol (Pae) and borneol (Bor). Solubility test, ternary phase diagrams and simplex lattice method were employed to screen and optimize the formulation of the mixture of Pae and Bor-loaded SMEDDS. After formed into microemulsions, the particle diameter (PD) was determined and a TEM was employed to observe the microemulsions' morphology. The contents of Pae and Bor were determined by gas chromatography. As a result, while ethyl oleate (EO) as the oil phase, cremophor EL35 (EL35) as surfactant and Transcutol HP (HP) as cosurfactant, the range of the microemulsion on the ternary phase diagram was larger than other combinations. And at a ratio of 20:45:35, the microemulsions' PD was about 34 nm and the polydispersity index (PI) was about 0.2. There were 16% of Pae, 2% of Bor, 16% of EO, 37% of EL35 and 29% of HP in the prepared SMEDDS. The preparation process of the Pae and Bor-loaded SMEDDS based on Xingbi Fang is simple and feasible. This study provides a reference for the researches on the related traditional Chinese medicine and the related components.
Acetophenones ; administration & dosage ; toxicity ; Administration, Intranasal ; Animals ; Bornanes ; administration & dosage ; toxicity ; Bufonidae ; Cilia ; drug effects ; Drug Combinations ; Drug Delivery Systems ; methods ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Emulsions ; Ethylene Glycols ; chemistry ; Female ; Male ; Nasal Mucosa ; drug effects ; Oleic Acids ; chemistry ; Particle Size ; Polyethylene Glycols ; chemistry ; Solubility ; Surface-Active Agents ; chemistry

The aim of this paper is to compare the cytotoxicity and cellular uptake efficiency of three kinds of poly(b-benzyl-L-amino) block-poly(ethylene glycol) nanoparticles (PXA-PEG-NPs) using Calu-3 cells, and select one as a nasal drug delivery vector for curcumin (Cur). Poly(gamma-benzyl-L-glutamate) block-poly(ethylene glycol) nanoparticles (PBLG-PEG-NPs), poly(gamma-benzyl-L-lysine) block-poly(ethyleneglycol) nanoparticles (PZLL-PEG-NPs) and poly(gamma-benzyl-L-aspartate) block-poly(ethylene glycol) nanoparticles (PBLA-PEG-NPs) were prepared by emulsion-solvent evaporation method. MTT assays were used to evaluate the cytotoxicity of PXA-PEG-NPs against Calu-3 cells. The cellular uptake of nanoparticles was visualized by an inverted fluorescence microscope and quantified by a flow cytometer. The results indicated that even at high concentration of 2 mg x mL(-1) the three nanoparticles had no cytotoxicity on Calu-3 cells. Compared to the curcumin solution, the three curcumin-loaded PXA-PEG-NPs showed significantly higher cellular uptake efficiency on Calu-3 cells (at equal concentration of curcumin with 5 microg x mL(-1) Cur solution), PBLG-PEG-NPs group was the highest. The cellular uptake increased with incubation time, and has positive correlation with nanoparticle concentration. In brief, PXA-PEG-NPs are conducive to delivery Cur into cells, and PBLG-PEG-NPs might be provided as a good nasal drug delivery carrier.
Adenocarcinoma ; metabolism ; pathology ; Administration, Intranasal ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; metabolism ; Aspartic Acid ; chemistry ; toxicity ; Cell Line, Tumor ; Cell Survival ; drug effects ; Curcumin ; administration & dosage ; metabolism ; Drug Carriers ; Ethylene Glycol ; chemistry ; toxicity ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Lysine ; chemistry ; toxicity ; Nanoparticles ; Particle Size ; Polyethylene Glycols ; chemistry ; toxicity ; Polyglutamic Acid ; analogs & derivatives ; chemistry ; toxicity