scholarly journals Preparation, Characterization and Pharmacokinetics Evaluation of Imperatorin Lipid Microsphere and Its Effect on Proliferation of MDA-MB-231

2018 ◽  
Author(s):  
Xinli Liang ◽  
Xulong Chen ◽  
Guowei Zhen ◽  
Tao Tang ◽  
Chunyan Wang ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Response Surface ◽  
Encapsulation Efficiency ◽  
Drug Loading ◽  
Experimental Conditions ◽  
Zeta Potentials ◽  
Preparation Conditions ◽  
Egg Lecithin ◽  
Central Composite ◽  
Lipid Microsphere

Imperatorin is a chemical compound belong to Linear furan coumarins. Imperatorin is attracting considerable attention because of its anti-tumor, antibacterial, anti-inflammatory, anticoagulant and inhibition of myocardial hypetrophy and other pharmacological efficacy. However, imperatorin has limited water solubility and preferable lipid solubility, we decided to design and synthesize imperatorin lipid microsphere, to optimize preparation conditions. The aim was to develop and formulate imperatorin lipid microsphere through nano emulsion technology and apply the response surface-central composite design to optimize the imperatorin lipid microsphere formulation. Influence of content of amount of egg lecithin(A), amount of poloxamer188(B), soybean oil for injection accounted for the total percentage of oil phase(C) were investigated. Integrated effect of dependent variables including particle size(Y1), polydispersity index(Y2), Zeta potentials(Y3), drug loading(Y4), encapsulation efficiency(Y5). Data of overall desirabiities were fitted to a second-order polynomial equation, through which three dimensional response surface graphs were described. Optimum experimental conditions were calculated by Design-Expert 8.06. Results indicated that the optimum preparation conditions were as follows: egg lecithin amount 1.39 g, poloxamer188 amount 0.21 g, soybean oil for injection amount 10.57%. Preparation of imperatorin lipid microsphere according to the optimum experimental conditions resulted in an overall desirability of 0.7286, while the particele size (168±0.54) nm, polydispersity index (PDI) (0.138±0.02), Zeta potentials (−43.5±0.5) mV, drug loading (0.833±0.27) mg·mL−1, encapsulation efficiency (90±1.27)%. The difference between observed and predicted values of the overall desirability of the optimum formulation was in range from 2.4% to 4.3%. Subsequently, using the Scanning electron microscopy to observe the micromorphology of imperatorin lipid microsphere, the result shows that round globular of relatively uniform and sizes within 200nm.The proliferation study of imperatorin lipid microsphere on MDA-MB-231 was investigated by MTT method. Furthermore, pharmacokinetics in Sprague Dawley rats were evaluated using orbital bleeding. A sensitive and reliable liquid chromatography with High Performance Liquid Chromatography (HPLC) method was established and validated for the quantification of imperatorin in rat plasma samples. The data were calculated by DAS (Drug and statistics) pharmacokinetic software version3.2.6 (China). Results demonstrated that imperatorin lipid microsphere can significantly enhance the bioavailability of imperatorin and can significantly inhibit MDA-MB-231 cell proliferating. In conclusion, our results suggersted that the response surface-central composite design is suitable for the optimized lipid microspere formulation. Imperatorin Lipid microsphere can improve the bioavailability of imperatorin and inhibit the proliferation of MDA-MB-231 than that of imperatorin.

scholarly journals Preparation, Characterization, and Pharmacokinetic Evaluation of Imperatorin Lipid Microspheres and Their Effect on the Proliferation of MDA-MB-231 Cells

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 236 ◽  
Author(s):  
Xinli Liang ◽  
Xulong Chen ◽  
Guowei Zhao ◽  
Tao Tang ◽  
Wei Dong ◽  
...  
Keyword(s):  
Particle Size ◽  
Response Surface ◽  
Encapsulation Efficiency ◽  
Drug Loading ◽  
Experimental Conditions ◽  
Zeta Potentials ◽  
Preparation Conditions ◽  
Egg Lecithin ◽  
Central Composite ◽  
Lipid Microsphere

Imperatorin is a chemical compound belonging to the linear furanocoumarins. Imperatorin is attracting considerable attention because of its antitumor, antibacterial, anti-inflammatory, and anticoagulant activities, inhibition of myocardial hypertrophy, and other pharmacological efficacies. However, imperatorin has limited water solubility and has better lipid solubility; thus, we decided to design and synthesize imperatorin lipid microspheres to optimize the preparation conditions. The aim was to develop and formulate imperatorin lipid microspheres through nanoemulsion technology and apply the response surface–central composite design to optimize the imperatorin lipid microsphere formulation. The influence of the amounts of egg lecithin, poloxamer 188, and soybean oil for injection on the total percentage of the oil phase was investigated. The integrated effect of dependent variables, including particle size, polydispersity index, zeta potentials, drug loading, and encapsulation efficiency, was investigated. Data of overall desirabilities were fitted to a second-order polynomial equation, through which three-dimensional response surface graphs were described. Optimum experimental conditions were calculated by Design-Expert 8.06. Results indicated that the optimum preparation conditions were as follows: 1.39 g of egg lecithin, 0.21 g of poloxamer 188, and 10.57% soybean oil for injection. Preparation of imperatorin lipid microspheres according to the optimum experimental conditions resulted in an overall desirability of 0.7286, with the particle size of 168 ± 0.54 nm, polydispersity index (PDI) of 0.138 ± 0.02, zeta potentials of −43.5 ± 0.5 mV, drug loading of 0.833 ± 0.27 mg·mL−1, and encapsulation efficiency of 90 ± 1.27%. The difference between the observed and predicted values of the overall desirability of the optimum formulation was in the range from 2.4% to 4.3%. Subsequently, scanning electron microscopy was used to observe the micromorphology of the imperatorin lipid microspheres, showing round globules of relatively uniform shape and sizes within 200 nm. The effect of imperatorin lipid microspheres on MDA-MB-231 proliferation was investigated by the MTT method. Furthermore, pharmacokinetics in Sprague-Dawley rats was evaluated using orbital bleeding. A sensitive and reliable liquid chromatography with the high-performance liquid chromatography (HPLC) method was established and validated for the quantification of imperatorin in rat plasma samples. The data were calculated by DAS (drug and statistics) Pharmacokinetic Software version 3.3.0 (Version 3.3.0, Shanghai, China). Results demonstrated that imperatorin lipid microspheres can significantly enhance the bioavailability of imperatorin and can significantly inhibit MDA-MB-231 cell proliferation. In conclusion, our results suggested that the response surface–central composite design is suitable for achieving an optimized lipid microsphere formulation. Imperatorin lipid microspheres can improve the bioavailability of imperatorin and better inhibit the proliferation of MDA-MB-231 cells as compared to imperatorin alone.

Application Research of Lipid Microsphere Biological Carrier Material on Prescription of Tanshinone II a Lipid Microsphere by Central Composite Design-Response Surface Method

2015 ◽  
Vol 1120-1121 ◽  
pp. 834-841
Author(s):  
Xin Li Liang ◽  
Dan Lv ◽  
Juan Luo ◽  
Xue Jing Guan ◽  
Zheng Gen Liao
Keyword(s):  
Response Surface ◽  
Encapsulation Efficiency ◽  
Average Particle Size ◽  
Egg Yolk ◽  
Tanshinone Iia ◽  
Average Particle ◽  
Surface Method ◽  
Size Stability ◽  
Central Composite ◽  
Lipid Microsphere

To optimize the prescription of tanshinone IIA lipid microspheres by central composite design method, and evaluate the quality. Through evaluating average particle size, stability constant and the encapsulation efficiency of the lipid microsphere to investigate the concentration of the egg yolk lecithin and the poloxamer and the percentage of Soybean oil in the total oil phase which may impact the properties of tanshinone IIA lipid microsphere. Building the mathematic relation between the index and factor by the binomial expression, according to the best mathematical model of the evaluation indicators to describe response surface and then to use response surface method to predict the best prescription which will be analysed. According to the prescription optimization to prepare tanshinone IIA lipid microsphere and evaluate its quality. The results showed that each index of the binomial equation fitting is good, the correlation coefficient of the average particle size, stability constant and the encapsulation efficiency are 0.97, 0.92 and 0.84 respectively. The optimized prescription is as follows: egg yolk lecithin1.38 g, F68 0.19 g, LCT 2 g, MCT 18 g, all the indexes of the optimized prescription are similar to the target values.

scholarly journals Central Composite Design for Response Surface Methodology and Its Application in Pharmacy

2021 ◽  
Author(s):  
Sankha Bhattacharya
Keyword(s):  
Central Composite Design ◽  
Response Surface ◽  
Response Surface Model ◽  
Fractional Factorial ◽  
Surface Model ◽  
Experimental Conditions ◽  
Design Models ◽  
Central Composite

The central composite design is the most commonly used fractional factorial design used in the response surface model. In this design, the center points are augmented with a group of axial points called star points. With this design, quickly first-order and second-order terms can be estimated. In this book chapter, different types of central composite design and their significance in various experimental design were clearly explained. Nevertheless, a calculation based on alpha (α) determination and axial points were clearly described. This book chapter also amalgamates recently incepted central composite design models in various experimental conditions. Finally, one case study was also discussed to understand the actual inside of the central composite design.

scholarly journals Optimization on Preparation Condition of Propolis Flavonoids Liposome by Response Surface Methodology and Research of Its Immunoenhancement Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ju Yuan ◽  
Yu Lu ◽  
Saifuding Abula ◽  
Yuanliang Hu ◽  
Jiaguo Liu ◽  
...  
Keyword(s):  
Response Surface Methodology ◽  
Response Surface ◽  
Theoretical Basis ◽  
Encapsulation Efficiency ◽  
Preparation Condition ◽  
Ethanol Injection ◽  
Preparation Conditions ◽  
Soybean Phospholipid

The aim of this study is to prepare propolis flavonoids liposome (PFL) and optimize the preparation condition and to investigate further whether liposome could promote the immunoenhancement activity of propolis flavonoids (PF). PFL was prepared with ethanol injection method, and the preparation conditions of PFL were optimized with response surface methodology (RSM). Moreover, the immunoenhancement activity of PFL and PFin vitrowas determined. The result showed that the optimal preparation conditions for PFL by response surface methodology were as follows: ratio of lipid to drug (w/w) 9.6 : 1, ratio of soybean phospholipid to cholesterol (w/w) 8.5 : 1, and speed of injection 0.8 mL·min−1. Under these conditions, the experimental encapsulation efficiency of PFL was 91.67 ± 0.21%, which was close to the predicted value. Therefore, the optimized preparation condition is very reliable. Moreover, the results indicated that PFL could not only significantly promote lymphocytes proliferation singly or synergistically with PHA, but also increase expression level of IL-2 and IFN-γmRNA. These indicated that liposome could significantly improve the immunoenhancement activity of PF. PFL demonstrates the significant immunoenhancement activity, which provides the theoretical basis for the further experimentin vivo.

Application of response surface method to carbamazepine removal in photo-ozonation reaction under alkaline condition

2013 ◽  
Vol 67 (1) ◽  
pp. 74-81 ◽  
Author(s):  
J. K. Im ◽  
K. D. Zoh
Keyword(s):  
Response Surface ◽  
Radical Scavenging ◽  
Alkaline Condition ◽  
H2o2 Concentration ◽  
Experimental Conditions ◽  
Scavenging Effect ◽  
Surface Method ◽  
Alkaline Conditions ◽  
Radical Scavenging Effect ◽  
Central Composite

In this study, the photo-ozonation reaction for carbamazepine (CBZ) removal was investigated under alkaline conditions. Response surface methodology based on a central composite design was used to obtain the optimum experimental conditions, and examine both main and interaction effects of the photo-ozonation reaction variables such as O3 concentration, H2O2 concentration and UV intensity. The level of O3 concentration significantly influenced CBZ removal (p < 0.001). CBZ removal increased with increasing both O3 and H2O2 concentration up to a certain level, whereas further increase in O3 and H2O2 concentration resulted in an adverse effect due to the hydroxyl radical scavenging effect. The optimum conditions for complete CBZ removal at pH 9 were found to be 0.89 mg of O3 l−1, 4.85 mg of H2O2 l−1 and 3.18 mW of UV intensity cm−2, respectively.

Enzyme-assisted Extraction for Optimized Recovery of Phenolic Bioactives from Peganum hermala Leaves Using Response Surface Methodology

2018 ◽  
Vol 17 (4) ◽  
pp. 349-354
Author(s):  
Qadir Rahman ◽  
Anwar Farooq ◽  
Amjad Gilani Mazhar ◽  
Nadeem Yaqoob Muhammad ◽  
Ahmad Mukhtar
Keyword(s):  
Response Surface Methodology ◽  
Response Surface ◽  
Enzyme Concentration ◽  
Coumaric Acid ◽  
Assisted Extraction ◽  
Pre Treatment ◽  
Optimized Conditions ◽  
Enzyme Complexes ◽  
Hydrolysis Of ◽  
Central Composite

This study investigates the effect of enzyme formulations (Zympex-014, Kemzyme dry-plus and Natuzyme) on recovery of phenolics from Peganum hermala (harmal) leaves, under optimized conditions using response surface methodology. As compared to the other enzyme complexes, the yield (34 g/100g) obtained through Zympex-014-assisted extraction was higher under optimized conditions such as time (75 min), temperature (70°C), pH (6.5) and enzyme concentration (5 g/100 g) using central composite design (CCD). Effectiveness of Zympex-014 towards hydrolysis of P. hermala leaves cell wall was examined by analyzing the control and enzyme-treated leave residues using scanning electron microscope (SEM). GC/MS characterization authenticated the presence of quercetin (1.44), gallic acid (0.23), caffeic acid (0.04), cinnamic acid (0.05), m-coumaric acid (0.23) and p-coumaric acid (0.37 μg/g) as the potent phenolics in Zympex-014 based extract. It can be concluded from the findings of the current work that pre-treatment of P. hermala leaves with Zympex-014 significantly enhanced the recovery of phenolics that supports its potential uses in the nutra-pharamaceutical industry.

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