The effects of ethylene glycol monoethyl ether (EGEE) on testicular cell populations in pubertal (5 weeks old) and adult (9 weeks old) male rats were investigated by a flow cytometric method. A total of 50 rats (in number, 25 pubertal and 25 adult rats) was divided into 5 experimental groups including 0 (control), 50, 100, 200, and 400 mg EGEE/kg of body weight. The animals were administered by gavage for 4 weeks. In adult rats, the treatment of EGEE at the dose of 400 mg/kg of body weight decreased significantly the populations of haploid, while it increased those of diploid and tetraploid cells. In pubertal rats, the treatment of EGEE at the dose of 400 mg/kg of body weight caused only minimal changes in the relative percent of testicular cell types. These results suggest that the effects of EGEE on testicular function in pubertal rats appear to be less pronounced than in adult rats.
Animals ; Dose-Response Relationship, Drug ; Ethylene Glycols/*toxicity ; Male ; Organ Size/drug effects ; Rats ; Sexual Maturation/*drug effects ; Solvents/*toxicity ; Spermatogenesis/*drug effects ; Testis/drug effects/*pathology ; Time Factors

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

AIMTo study the effect of negatively charged and positively charged self-microemulsifying systems (SMES) on the cellular tight junction complex was to be investigated at molecular cell level.

METHODSHuman intestinal epithelial Caco-2 cell model was established. Effect of formulations on the transepithelial electrical resistance (TEER) and permeability of the paracellular transport marker mannitol were measured to evaluate the cell integrity. Changes in subcellular localization of the tight junction protein zona occludens 1 (ZO-1) and cytoskeleton protein actin by immunofluorescence were also assessed after treatment of two SMESs in different dilutions.

RESULTSThe TEER of cell monolayers was not markedly affected by negatively charged SMES in different dilutions. The positively charged SMES could significantly decrease the TEER (P < 0.05) in three dilutions. The full recovery of TEER was found after the treatment of lower dilution for 2 h, then cultured for 48 h, while the recovery of TEER was 81.3% of control in 1 : 50 dilution. Two SMESs could enhance the apparent permeability coefficient of mannitol (2.9 - 64.6 folds), which depended on the dilution times. The immunofluorescent results indicated that the distribution of ZO-1 and actin were discrete in cell membrane after the treatment of formulation. Since the positively charged microemulsion could bind to the epithelial cell membrane by electrostatic interaction, the actin of the cells undergone some kind of stress stimulated by the higher concentration of microemulsion was more markedly affected than the negatively charged SMES. Effect of formulations on ZO-1 and actin relied on the dilution.

CONCLUSIONSMES is able to enhance the paracellular transport marker mannitol. The mechanism of opening of tight junctions by SMES might be the change of distribution of ZO-1 and actin.

Actins ; metabolism ; Caco-2 Cells ; Cell Membrane ; drug effects ; metabolism ; Cell Survival ; drug effects ; Drug Delivery Systems ; Electric Impedance ; Emulsions ; administration & dosage ; pharmacology ; toxicity ; Ethylene Glycols ; pharmacology ; toxicity ; Glycerides ; Glycerol ; analogs & derivatives ; pharmacology ; toxicity ; Humans ; Mannitol ; pharmacokinetics ; Membrane Proteins ; metabolism ; Organic Chemicals ; pharmacology ; toxicity ; Phosphoproteins ; metabolism ; Protein Transport ; Tight Junctions ; drug effects ; metabolism ; Zonula Occludens-1 Protein

OBJECTIVETo investigate the effect of 2-phenoxyethanol on potency of Sabin inactivated poliomyelitis vaccine (IPV).

METHODSSabin IPV samples containing 5 mg or 7 mg 2-phenoxyethanol each dosage respectively were placed separately at 4 degrees C, 37 degrees C for 2 days and 7 days. D-antigen contents were tested with ELISA method. Then neutralizing antibodies in mice and guinea pigs were detected. The safety experiment was performed according to unusual toxicity test of China requirement for biological product.

RESULTSAfter addition of 2-phenoxyethanol, the I, II, and III D-antigen contents of Sabin IPV did not change. The antibody levels in mice and guinea pigs were not different between experimental group and control group. Animals were safe during observation period.

CONCLUSION2-Phenoxyethanol had no effect on potency and safety of Sabin IPV. It can be used as antiseptic for Sabin IPV.

Animals ; Anti-Infective Agents, Local ; administration & dosage ; pharmacology ; toxicity ; Antigens, Viral ; analysis ; immunology ; Body Weight ; drug effects ; Cercopithecus aethiops ; Drug Stability ; Enzyme-Linked Immunosorbent Assay ; Ethylene Glycols ; administration & dosage ; pharmacology ; toxicity ; Guinea Pigs ; Mice ; Neutralization Tests ; Poliovirus Vaccine, Inactivated ; administration & dosage ; immunology ; toxicity ; Vero Cells