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OBJECTIVE： To establish a method for content determination of indapamide （IDP）-β-cyclodextrin （β-CD） inclusion compound， optimize the preparation technology， carry out phase identification and in vivo release study of it. METHODS： UV spectrophotometry was used to determine the content of IDP in IDP-β-CD inclusion compound. IDP-β-CD inclusion compound was prepared by the solution-stirring method and the preparation technology was optimized by the orthogonal experiment using inclusion rate as index. The inclusion rate and drug-loading rate were compared between different drying methods. Phase identification of IDP-β-CD inclusion compound was verified by IR and DSC. The cumulative release rate of inclusion compound was tested by in vitro experiment. RESULTS： The linear range of concentration of IDP was 2.0-14.0 μg/mL （r＝0.999 7）. The quantitative limit and detection limit were 0.204， 0.067 μg/mL， respectively. RSDs of precision， stability and repeatability tests were all less than 2％. The recoveries range was 98.8％-101.8％（RSD＝1.10％，n＝6）. The optimum technology conditions were as follows the molar ratio of β-CD to IDP was 3 ∶ 1， the inclusion time was 3 h， and the stirring speed was 300 r/min. Average inclusion rate of IDP-β-CD inclusion compound was 72.81％. IR and DSC analysis showed that IDP and β-CD formed inclusion compound through physical interaction. After spray drying， the inclusion rate and drug-loading rate of IDP-β-CD inclusion compound were （60.96±0.25）％ and （4.18±0.12）％. After freeze-drying， the inclusion rate and drug-loading rate of IDP-β-CD inclusion compound were （77.31±0.51）％ and （5.31±0.27）％. Accumulative release rates of IDP， IDP-β-CD inclusion compound （by freeze-drying and spray drying） were 37.2％， 42.5％ and 81.9％ within 12 h， respectively. Compared with IDP raw material， accumulative release rate of IDP-β-CD inclusion compound increased significantly after spray drying. CONCLUSIONS： Established method is simple and accurate. The optimal preparation technology of inclusion compound is stable and feasible. IDP-β-CD inclusion compound is prepared successfully. The inclusion compound prepared by spray drying shows higher release rate.
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Objective To observe the effect of Rhy-SLN on the proliferation of rat vascular smooth muscle cells (VSMC) induced by TGF-β1, and explore the mechanism. Methods The primary culture of rat thoracic aortic vascular smooth muscle cells was studied by tissue block culture method. The cells were divided into the control group, TGF-β1 group, TGF-β1+ the high, medium and low dosage groups of Rhy-SLN. In addition to the control group, the cells of the other groups were involved in the intervention of TGF-β1 of 20 g/L, and the high, medium and low dosage groups of Rhy-SLN cells were involved in the intervention of 25, 50, 100 mg/L of the hook teng solid lipid nanoparticles. After 24 hours of culture, MTT assay was used to detect cell proliferation inhibition rate in each group, and the cell cycle was detected by flow cytometry. The expression of c-myc and c-Fos protein in each group was detected by Western blot method. Results Compared with the TGF-β1 group, the absorbance value (0.457 ± 0.046 vs. 0.975 ± 0.049) of TGF-β1+ rhy-sln high dose group significantly decreased (P<0.01); the number of S phase cells (15.87% ± 2.47%, 15.23% ± 1.69%, 17.02% ± 2.87% vs.38.58% ± 2.68%)of TGF-β1+rhy-sln in each dose group significantly decreased(P<0.01);The c-myc(48.65 ±3.65,50.69 ± 4.16,55.29 ± 3.67 vs.68.21 ± 3.25)and c-Fos(38.78 ± 4.25,43.56 ± 3.69,46.58 ± 3.57 vs.66.54 ± 4.09) of the TGF-β1+ rhy-sln each dose group significantly decreased (P<0.01). Conclusions The Rhy-SLN can inhibit the proliferation of VSMC in rats induced by TGF-β1.Its mechanism is related to the conversion of G0/G1 phase to the S phase and the expression of the reduction of c-myc and c-fos protein.
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OBJECTIVE:To optimize the formulation of nanostructured lipid carriers loaded with lornoxicam (LN-NLC). METHODS:Emulsification-solvent evaporation method was used to prepare the LN-NLC. Using drug-lipid ratio,dosage of soy lec-ithin,liquid-lipid ratio (proportion of liquid lipid to total lipid) and dosage of emulsifier as factors,the overall normalized value was calculated by particle size,Zeta potential and entrapment efficiency as indexes was used as comprehensive index. Central com-posite design-response surface method was used to optimize the formulation and investigate the appearance and stability of prepared LN-NLC. RESULTS:The optimal formulation were as follows as drug-lipid ratio of 1:50,dosage of soy lecithin of 162.5 mg,liq-uid-lipid ratio of 25% and emulsifier dosage of 958.2 mg. The particle size of prepared LN-NLC was(96.9±3.3)nm,Zeta poten-tial was(-16.1±0.3)mV,entrapment efficiency was(60.1±0.9)%(n=3),which showed relative error of 2.47%,-4.55%,-0.17%with predicted value,respectively. The prepared LN-NLC was spherical. It had no obvious changes in particle size and Ze-ta potential in sealed storage for 30 d in 4 ℃,and the entrapment efficiency only declined 1.2%. CONCLUSIONS:The LN-NLC formulation is successfully optimized,and the LN-NLC has good stability.
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OBJECTIVE:To optimize the formulation of nanostructured lipid carriers loaded with lornoxicam (LN-NLC). METHODS:Emulsification-solvent evaporation method was used to prepare the LN-NLC. Using drug-lipid ratio,dosage of soy lec-ithin,liquid-lipid ratio (proportion of liquid lipid to total lipid) and dosage of emulsifier as factors,the overall normalized value was calculated by particle size,Zeta potential and entrapment efficiency as indexes was used as comprehensive index. Central com-posite design-response surface method was used to optimize the formulation and investigate the appearance and stability of prepared LN-NLC. RESULTS:The optimal formulation were as follows as drug-lipid ratio of 1:50,dosage of soy lecithin of 162.5 mg,liq-uid-lipid ratio of 25% and emulsifier dosage of 958.2 mg. The particle size of prepared LN-NLC was(96.9±3.3)nm,Zeta poten-tial was(-16.1±0.3)mV,entrapment efficiency was(60.1±0.9)%(n=3),which showed relative error of 2.47%,-4.55%,-0.17%with predicted value,respectively. The prepared LN-NLC was spherical. It had no obvious changes in particle size and Ze-ta potential in sealed storage for 30 d in 4 ℃,and the entrapment efficiency only declined 1.2%. CONCLUSIONS:The LN-NLC formulation is successfully optimized,and the LN-NLC has good stability.
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AIM:To put forward three-level design(Box-Behnken design)for fitting response surfaces to optimize the extraction technology of total flavonoids from Hypericum ascyron L.METHODS:Four factors,including temperature,reflux time,concentration of ethanol,ratio of solvent to raw material were used to examine the yield of total flavonoids.Prediction was carried out through comparing the observed and predicted values.RESULTS:The results suggested that ethanol concentration and extraction temperature were two statistically significant factors.The optimum conditions of extraction process consisted of the ratio(mL:g)of solvent to material(13.3:1),ethanol concentration(53.2%),extraction temperature(78.7℃)and extraction time(2.3h).Regression coefficient of binomial fitting complex model was as high as 0.984 6.Bias between observed and predicted values was-4.01%.CONCLUSION:Box-Behnken design is success in optimizing the extaction in close agreement with the predicted values of the mathematic model.
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AIM:To put forward three-level design(Box-Behnken design) for fitting response surfaces to optimize the extraction technology of total flavonoids from Hypericum ascyron L.METHODS:Four factors,including temperature,reflux time,concentration of ethanol,ratio of solvent to raw material were used to examine the yield of total flavonoids.Prediction was carried out through comparing the observed and predicted values.RESULTS:The results suggested that ethanol concentration and extraction temperature were two statistically significant factors.The optimum conditions of extraction process consisted of the ratio(mL:g)of solvent to material(13.3:1),ethanol concentration(53.2%),extraction temperature(78.7℃)and extraction time(2.3h).Regression coefficient of bino-mial fitting complex model was as high as 0.984 6.Bias between observed and predicted values was -4.01%.CONCLUSION:Box-Behnken design is success in optimizing the extaction in close agreement with the predicted values of the mathematic model.