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Formulation optimization of scutellarin-loaded HP-β-CD/chitosan nanoparticles using response surface methodology with box–behnken design

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Asian Journal of Pharmaceutical Sciences 2017年第4期12卷 378-385页

作者： Shanshan Liu Paul C.Ho National University of Singapore

The aim of this paper is to investigate and optimize the preparation of scutellarin(SCU)-loaded HP-β-CD/chitosan(CS) nanoparticles(CD/CS-SCU-NPs). CD/CS-SCU-NPs were prepared by ionic cross-linking method and the process and formulation variables were optimized using response surface methodology(RSM) with a three-level, three factor box–behnken design(BBD).The independent variables were the added amounts of CS, sodium tripolyphosphate(TPP)and Pluronic F-68 during the preparation. Dependent variables(responses) were particle size and entrapment efficiency. Mathematical equations and respond surface plots were used to correlate independent and dependent variables.The preparation process and formulation variables were optimized to achieve minimum particle size and maximum entrapment efficiency by calculating the overall desirability value(OD). The optimized NP formulation was characterized for particle size, PDI, zeta potential, entrapment efficiency and in vitro drug release.According to the results, an optimized CD/CS-SCU-NP formulation was prepared. Results for particle size, PDI, zeta potential and entrapment efficiency were found to be around 200 nm,0.5, 25 mV, and 70% respectively. For in vitro study, the release of SCU from the NPs exhibited a biphasic release and was in accordance with Higuchi equation. The optimized preparation was simple with the probability for industrialization. The combination use of RSM, BBD and overall desirability values could provide a promising application for incorporating CD into CS nanoparticles as drug delivery carrier and help develop lab-scale procedures.

关键词： Scutellarin Response surface methodology box–behnken design Chitosan HP-β-CD Nanoparticles

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Oxidative desulfurization of model and real oil samples using Mo supported on hierarchical alumina–silica: Process optimization by box–behnken experimental design

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Chinese Journal of Chemical Engineering 2019年第11期27卷 2759-2770页

作者： Nasim Ghorbani Gholamreza Moradi Catalyst Research Center Department of Chemical EngineeringFaculty of EngineeringRazi UniversityKermanshahIran

The catalytic performance of Mo supported on hierarchical alumina–silica(Si/Al = 15) with Mo loadings of 3, 6 and 15 wt% was investigated for the oxidative desulfurization(ODS) of model and real oil samples. Hierarchical alumina–silica(h Al–Si) was synthesized by economical and ecofriendly silicate-1 seed-induced route using cetyltrimethylammonium bromide(CTAB) as mesoporogen. The effect of CTAB on the structure of catalyst was studied by characterization techniques. The results revealed that 6%Mo/h Al–Si had the highest sulfur removal compared to the other catalyst loadings. The effect of operating parameters was evaluated using box–behnken experimental design. The optimal desulfurization conditions with the 6%Mo/h Al–Si catalyst were determined at oxidation temperature of 67 ℃, oxidation time of 42 min, H2O2/S molar ratio of 8 and catalyst dosage of 0.008 g·ml^-1 for achieving a conversion of 95%. Under optimal conditions, different sulfur-containing compounds with initial concentration of 1000 ppm, Dibenzothiophene(DBT), Benzothiophene(BT) and Thiophen(Th), showed the catalytic oxidation reactivity in the order of DBT > BT>Th. According to the regeneration experiments, the 6%Mo/h Al–Si catalyst was reused 4 times with a little reduction in the performance. Also, the total sulfur content of gasoline and diesel after ODS process reached 156.6 and 4592.2 ppm, respectively.

关键词： Oxidative desulfurization Hierarchical alumina–silica Silicate-1 seed-induced route box–behnken experimental design

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Preparation of CaP/pDNA nanoparticles by reverse micro-emulsion method: Optimization of formulation variables using experimental design

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Asian Journal of Pharmaceutical Sciences 2017年第2期12卷 179-186页

作者： Wenpan Li Shasha Jing Xiu Xin Xirui Zhang Kang Chen Dawei Chen Haiyang Hu Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University

In this study, the CaP/pDNA nanoparticles were prepared using Triton X-100/Butanol/Cyclohexane/Water reverse microemulsion system. Optimization of preparation conditions was based on evaluation of particle size by box–behnken design method. The particle sizes of the optimized CaP/pDNA nanoparticles were found to be 60.23 ± 4.72 nm, polydispersity index was 0.252 and pDNA encapsulate efficiency was more than 90%. The optimized CaP/pDNA nanoparticles have pH sensitivity and biocompatibility. Further, optimized CaP/pDNA nanoparticles showed higher transfection efficiency.

关键词： CaP nanoparticles pDNA Reverse microemulsion method box–behnken design Transfection and expression

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Preparation and evaluation of poly(L-histidine) based pH-sensitive micelles for intracellular delivery of doxorubicin against MCF-7/ADR cells

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Asian Journal of Pharmaceutical Sciences 2017年第5期12卷 433-441页

作者： Nan Jia Yuqing Ye Qi Wang Xiuli Zhao Haiyang Hu Dawei Chen Mingxi Qiao Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University

In this study, a p H-sensitive micelle self-assembled from poly(L-histidine) based triblock copolymers of poly(ethylene glycol)–poly(D,L-lactide)–poly(L-histidine)(mPEG-PLA-PHis) was prepared and used as the intracellular doxorubicin(Dox) delivery for cancer chemotherapy. Dox was loaded into the micelles by thin-film hydration method and a box–behnken design for three factors at three levels was used to optimize the preparations. The optimized mPEG-PLA-Phis/Dox micelles exhibited good encapsulation efficiency of 91.12%,a mean diameter of 45 nm and narrow size distribution with polydispersity index of 0.256.In vitro drug release studies demonstrated that Dox was released from the micelles in a p Hdependent manner. Furthermore, the cellular evaluation of Dox loaded micelles displayed that the micelles possessed high antitumor activity in vitro with an IC50 of 35.30 μg/ml against MCF-7/ADR cells. The confocal microscopy and flow cytometry experiments indicated that m PEG-PLA-Phis micelles mediated efficient cytoplasmic delivery of Dox with the aid of poly(Lhistidine) mediated endosomal escape. In addition, blank m PEG-PLA-Phis micelles were shown to be nontoxic to MCF-7/ADR cells even at a high concentration of 200 μg/ml. The pHsensitive mPEG-PLA-PHis micelles have been demonstrated to be a promising nanosystem for the intracellular delivery of Dox for MDR reversal.

关键词： Doxorubicin(Dox) mPEG-PLA-Phis pH sensitive micelles box–behnken design

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Fermentative Production of Mycelial Chitosan from Zygomycetes: Media Optimization and Physico-Chemical Characterization

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Advances in Bioscience and Biotechnology 2014年第12期5卷 940-956页

作者： Pradnya N. Vaingankar Archana R. Juvekar Department of Pharmaceutical Science and Technology Institute of Chemical Technology Mumbai India

The present study focused on production of mycelial chitosan from fungal mycelium by submerged fermentation with ecologically more balanced process. Different fungal strains were screened and Absidia butleri NCIM 977 was found to produce the highest mycelial chitosan. The one-factor-at-a-time method was adopted to investigate the effect of batch time, environmental factors (i.e. initial pH and temperature) and medium components (i.e. carbon and nitrogen) on the yield of mycelial chitosan. Among these variables, the optimal condition to increase in yield of mycelial chitosan was found to be batch time (72 h), pH (5.5), temperature (30°C), carbon source (glucose) and nitrogen source (tryptone and yeast extract). Subsequently, a three-level box– behnken factorial design was employed combining with response surface methodology (RSM) to maximise yield of mycelial chitosan by determining optimal concentrations and investigating the interactive effects of the most significant media components (i.e. carbon and nitrogen sources). The optimum value of parameters obtained through RSM was glucose (1.58%), tryptone (1.61%) and yeast extract (1.11%). There was an increase in mycelial chitosan yield after media optimization by one-factor-at-a-time and statistical analysis from 683 mg/L to 1 g/L. Mycelial chitosan was characterized for total glucosamine content (80.68%), degree of deacetylation (DD) (79.89%), molecular weight (8.07 × 104 Da) and, viscosity (73.22 ml/g). The results of this study demonstrated that fungi are promising alternative sources of chitosan with high DD and high purity.

关键词： Mycelial Chitosan Submerged-State Fermentation Response Surface Methodology box–behnken Design Characterization

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