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OBJECTIVE@#To design and synthesize folate-modified pH-responsive chitosan-based nanomicelles and investigate the anti-tumor activity of the drug-loaded micelles.@*METHODS@#CHI-DMA was obtained by reductive amination reaction of aldehyde-based chitosan and hydrophilic amine compounds, and CHI-DMA-LA was obtained by condensation reaction with lauric acid; FA-CHI-DMA-LA was obtained after modification with folic acid (FA). The drug-loaded nanomicelles FA-CHI-DMA-LA/DOX were assembled by solvent change method. The physicochemical properties of polymers were characterized by hydrogen nuclear magnetic resonance and transmission electron microscope. The particle size and surface potential were determined by dynamic light scattering method. Folic acid access rate, doxorubicin (DOX) loading rate and entrapped efficiency were measured by UV-vis spectrophotometer. The drug release properties of DOX-loaded micelles were monitored by fluorescence spectrophotometer at different pHs (7.4, 6.5, 5.0). The cytotoxicity against human oral cancer KB cells was detected by MTT assay. Fluorescence microscope and flow cytometry were applied to investigate the phagocytosis of DOX-loaded micelles on KB cells.@*RESULTS@#FA-CHI-DMA-LA was synthesized. The particle sizes of FA-CHI-DMA-LA-1 and FA-CHI-DMA-LA-2 micelles which used for the subsequent experiments were (73±14) nm and (106±15) nm, zeta potential were (15.59±1.98) mV and (21.20±2.35) mV, respectively. The drug loading rates of drug-loaded micelles FA-CHI-DMA-LA-1/DOX and FA-CHI-DMA-LA-2/DOX are (4.08±1.12)%and (4.12±0.44)%, respectively. drug release is pH-responsive, with cumulative release of DOX up to 37%and 36%at pH 5.0, which is about 1.5 times higher than that of pH 7.4. For FA-CHI-DMA-LA micelles with 1.25 to 125 μg/mL concentration, the survival rate of KB cells is more than 70%after incubation for 24 hours. The cell uptake of FA-CHI-DMA-LA/DOX micelles was enhanced compared to CHI-DMA-LA/DOX, and the cell uptake was higher in incubation without FA medium than that with FA. Compared with free DOX or CHI-DMA-LA/DOX, FA-CHI-DMA-LA/DOX nanomicelles showed higher cyctoxicity to KB cells, especially the FA-CHI-DMA-LA-2/DOX nanomicelles, the cell survival rate was about 17% after incubation for 24 hours.@*CONCLUSIONS@#FA-modified chitosan-based nanomicelle with good biocompatibility was successfully prepared, which exhibits tumor microenvironmental pH responsive drug release and tumor targeting.
Subject(s)
Humans , Antineoplastic Agents , Chitosan , Doxorubicin , Drug Carriers , Folic Acid , Micelles , Nanostructures , PolymersABSTRACT
Objective To optimize the extraction process of Paeoniae radix alba. Methods Extraction rates of paeoniflorin and total glucosides from Paeoniae radix alba and yield of dry extract were served as research indexes. Extraction process was optimized by central composite design-response surface methodology. Results Optimum condition of extraction technology was to extract 2 times with 9-fold of 85.00% ethanol for 100 min each time. Results of the three batches of confirmatory test were accordant with the predicted values. Conclusion The observed and predicted values were close to each other,and the optimum formulation by CCD-RSM was successful. The established model has a reliable predictability. The optimum extraction process is reasonable,stable and feasible.
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The study introduced the general evaluation indicator system for community health services in Shanghai and its characteristics,analyzing the results of the comprehensive evaluation from the aspects of regions and institutions.From six aspects of financial input,human resource construction, operation mechanism,family doctor system,information system construction and the application of the comprehensive evaluation results,the paper recommended on deepening the reform of community health services.
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Objective To study the antidepressant effect of Yiyukang and to explore its possible mechanism.Methods By using the mice forced-swimming models,mice tail suspension models and mice stereotyped behavior models,the antidepressant effect of Yiyukang and its mechanism were observed.Result In the mice forced-swimming test,the im- mobility-time was significantly reduced by high and medium dosage Yiyukang with the reduced rate being 21.65% and 24.84%(P＜0.01).The high dosage can also reduce the immobility time of tail-suspension mice with the rate of 29.58%(P＜0.01).Yiyukang can strengthen the mice head shaking behavior and had synergistic action with 5- HTP on reducing stereotyped behavior in mice.Conclusion Yiyukang has certain antidepressant effect,and the mecha- nism may be associated with promoting the actions of 5-hydroxytryptamine and dopamine in mice brain.