ABSTRACT
Aim Paclitaxel(PTX)has shown an effect against human cancer. However, serious drawbacks hamper PTX clinical use.Overcoming paclitaxel limi-tations is one of the best approaches to enhance water solubility.Methods In this study,water-soluble pa-clitaxel prodrug was prepared,folic acid-polyethylene glycol-glutamic-paclitaxel (FA-PEG-Glu-PTX ) com-posed of folic acid (FA,target),amino acids (Glu, linker),and polyethylene glycol(PEG)in order to im-prove the solubilization and stability. The chemical structure and physicochemical property of prodrug were measured by LC-MS,solubility,drug release rate to e-valuate the antitumor activity and cytotoxicity of FA-PEG-Glu-PTX.MTT assays were conducted on MDA-MB-231,MCF-7,A549 and HELF cell lines.FA-PEG-Glu-PTX prodrugs were labeled with 5 amino flu-orescence visible fluorescent dye (5 AF ) for fluores-cence microscopy.Results The successful conjugation of FA-PEG-Glu-PTX was confirmed by LC-MS,and had better water solubility,release rate curve.In vitro studies indicated that foliate receptor(FR-α)mediated uptake of PTX-conjugated multi-small molecules carri-ers induced highly targeting ability,and antitumor ac-tivity,as well as reduced side toxicity effects of PTX. Conclusion FA-PEG-Glu-PTX has a good antitumor activity.
ABSTRACT
ObjectiveTo explore the changes of the levels of cytokines in patients with first-episode depression and the effect on the levels of cytokines after the treatment with duloxetine.MethodsThe serum levels of interleukin 1 ( IL-1 ),interleukin 6 ( IL-6 ),tumor necrosis factor-alpha ( TNF-αt ),interleukin4 ( IL-4 ),interleukin10(IL-10) were measured in 38 patients with depression before and after duloxetine treatment by enzyme linked immunosorbent assay(ELISA).HAMD score were assessed at pre- treatment and post-treatment to assess curative effect.The control group was 30 healthy individuals.All data were statisticaly analyzed by SPSS.ResultsBefore treatment,the HAMD score and the levels of serum IL-6,TNF-α,IL-1 in first-episode depressant patients were remarkablely higher than those in the control group( IL-6:( 10.66 ± 3.12 ) pg/ml vs (2.72 ± 0.91 ) pg/ml ;TNF-α:(77.49 ±3.12) pg/ml vs (37.48 ±5.87) pg/ml; IL-1:(39.09 ± 3.77 ) pg/ml vs ( 10.31 ± 1.05 ) pg/ml ),the levels of serum IL-4 and IL-10 in first-episode depressant patients were remarkablely lower than those in the control group(P＜0.05,P＜0.01 ).The HAMD score and the levels of serum IL-6,TNF-α,IL-1 in post-treatment were remarkablely lower than pre-treatment (P ＜ 0.05 ),but which were still higher than the control group(P＜ 0.05 ).The levels of serum IL-4 and IL-10 in post-treatment were remarkablely increased than pre-treatment(P＜0.05).The levels of serum IL-6,TNF-α,IL-1 were positively correlated with the HAMD score( r =0.667,0.486,0.727,P ＜0.01 ),but the levels of serum IL-4 and IL-10 were negatively correlated with the HAMD scorae ( r=-0.433,-0.269,P＜0.05,P＜ 0.01 ).ConclusionsThe first-episode depressant patients show immune disorder induced by cytokines.Anti-depressant activity of duloxetine may participate in the regulation of cytokines and Th1/Th2 unbalance.