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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH · 2019 · IF 3.375

Process Intensified Synthesis of Rare-Earth Doped β-NaYF4 Nanorods toward Gram-Scale Production

Yiran Jiao,Yuan Pu,Jie-Xin Wang,Dan Wang,Jian-Feng Chen

We reported the process intensified synthesis of β-NaYF4 nanorods based on the traditional hydrothermal methods. A high-gravity rotating packed bed (RPB) reactor was used to intensify the mass transfer and micromixing of the precursors for critical nuclei. The proposed high gravity RPB assisted strategy is easy-to-perform for scale-up. The influence of reaction conditions was explored and the possible mechanism of the formative of β-NaYF4 nanorods was discussed. Accordingly, over 1 g of pure β-phase NaYF4:Gd3+/Yb3+/Er3+ nanorods with well-defined morphology and structure were prepared via one batch reaction. The rare-earth doped β-NaYF4 nanorods are highly dispersible in organic solvents with intense upconversion luminescence under near-infrared (NIR) light irradiation. The translucent NIR detector card of nanocomposites of poly(methyl-methacrylate) and the nanoroads was fabricated accordingly. The photosensitive region can also be activated by illuminating the back of the card, which is useful when aligning two beams to overlap.

CAS / MDL: 80-62-6
研究领域: 材料科学 · 纳米技术 · 化学工程 · 光学
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APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY · 2021 ·Vol. 193 ·期 7 ·2029-2042 · IF 2.926

Development of a Combination Fermentation Strategy to Simultaneously Increase Biomass and Enzyme Activity of d-amino Acid Oxidase Expressed in Escherichia coli

Xu Jian-Miao,Cao Hui-Ting,Wang Ming,Ma Bao-Jian,Wang Liu-Yu,Zhang Kai,Cheng Feng,Xue Ya-Ping,Zheng Yu-Guo

d -amino acid oxidase (DAAO) is widely used in the industrial preparation of l -amino acids, and cultivating Escherichia coli ( E. coli ) expressing DAAO for the biosynthesis of l -phosphinothricin ( l -PPT) is very attractive. At present, the biomass production of DAAO by fermentation is still limited in large-scale industrial applications because the expression of DAAO during the fermentation process inhibits the growth of host cells, which limits higher cell density. In this study, the factors that inhibit the growth of bacterial cells during a 5-L fed-batch fermentation process were explored, and the fermentation process was optimized by co-expressing catalase (CAT), by balancing the biomass and the enzyme activity, and by adding exogenous d -alanine ( d -Ala) to relieve the limitation of DAAO on the cells and optimize fermentation. Under optimal conditions, the DO-STAT feeding mode with DO controlled at 30% ± 5% and the addition of 27.5 g/L lactose mixed with 2 g/L d -Ala during induction at 28 °C resulted in the production of 26.03 g dry cell weight (DCW)/L biomass and 390.0 U/g DCW specific activity of DAAO; an increase of 78% and 84%, respectively, compared with the initial fermentation conditions. The fermentation strategy was successfully scale-up to a 5000-L fermenter.

研究领域: 生物技术 · 微生物学 · 酶学 · 工业发酵
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2024 · IF 5.3

High-throughput preparation, scale up and solidification of andrographolide nanosuspension using hummer acoustic resonance technology

Xiaoyang Zhang,Li Wang,Yao Zhang,Sijun Wu,Xin Sha,Wei Wu,Wenlong Li

The aim of this study was to rapidly develop a sufficiently robust andrographolide nanosuspension (AG-NS) system using hummer acoustic resonance (HAR) technology. The system can effectively improve the dissolution properties of AG, while having high stability and scale-up adaptability. The formulation of AG-NS was optimized in a high-throughput manner using HAR technology and the preparation process was optimized stepwise. Optimal AG-NS with Z-Ave = 223.99 ± 3.16 nm, PDI=0.095 ± 0.007 and zeta potential = –33.20 ± 0.58 mV was successfully prepared with Polyvinylpyrrolidone K30 and Sodium dodecyl sulfate. The optimal prescription was successfully scaled up 100 and 150 times using HAR technology, which was the initial exploration of its commercial scale production. AG-NS was solidified using freeze drying and fluid bed technology, respectively. The optimal AG-NS and its solidified products were exhaustively characterized using various analytical techniques. The high energy input of HAR technology and drying process converted part of the drug into the amorphous state. The in-vitro drug dissolution studies demonstrated relatively higher drug dissolution for AG-NS and its solidified products compared to controls at both the dissolution media (pH 1.2 buffer and pH 6.8 buffer). AG-NS and its solidified products successfully maintained their physical stability in short-term stability and accelerated stability experiments, respectively.

CAS / MDL: 9004-64-2
研究领域: 药学 · 纳米技术 · 药物递送系统 · 制药工程
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GREEN CHEMISTRY · 2021 ·Vol. 23 ·期 11 ·4087-4094 · IF 10.182

A 3D-printed continuous flow platform for the synthesis of methylaluminoxane

Yirong Feng,Jie Wang,Haomiao Zhang,Jingdai Wang,Yongrong Yang

We present the first 3D-printed continuous flow platform for the green synthesis of methylaluminoxane (MAO), the most powerful olefin polymerization co-catalyst with metallocenes. This platform consists of an on demand designed and 3D-printed liquid–liquid mixer, reactors, and a separator to enable precise control of the highly exothermic hydrolytic reaction of trimethylaluminum (TMA). Moreover, during TMA hydrolysis, solid by-products are formed and methane gas is released, both of which impede reagents blending and MAO formation, thereby making it a challenging implementation with a continuous flow strategy. By optimizing the platform configuration and reaction conditions, we obtain an MAO product with a high yield and superior co-catalytic activity, as measured by two different groups of polymerization tests. This low-volume process, which avoids the accumulation of any explosive reagents, offers long-term stability and inherent safety and facilitates scale up with multiple reactors. In addition, such an efficient, scalable, and safe flow platform preserving the mixing and heat transfer advantages delivers insights into handling other highly exothermic reactions involving the formation of solids and gases.

研究领域: 化学工程 · 材料科学 · 催化 · 绿色化学
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS · 2024 · IF 4.4

Acoustic resonance technology and quality by design approach facilitate the development of the robust tetrandrine nano-delivery system

Xiaoyang Zhang,Xi Wang,Jianlu Qu,Yao Zhang,Cunhao Li,Wei Wu,Wenlong Li

The aim of this study was to develop a sufficiently robust tetrandrine (Tet) nano-delivery system using acoustic resonance (AR) technology and freeze-drying technology. This system can effectively improve the solubility and dissolution properties of Tet, along with high stability and scale-up adaptability. Firstly, 54 stabilizers were screened simultaneously in a high-throughput manner with the help of AR technology to fully explore the optimal prescription space of tetrandrine nanosuspension (Tet-NS). The Plackett-Burman design was used to screen for critical variables severely affecting the quality of Tet-NS. The Box-Behnken design was used to investigate and optimize critical variables to obtain optimal nanosuspensions. The optimal prescription was successfully scaled up by 100 times, which was the initial exploration of its commercial scale production. Solidification studies have shown that formulations with 2.44% fructose as the cryoprotectant have excellent redispersibility. Compared with pure Tet, Tet in Tet-NS showed a significant increase in solubility and dissolution rate in water. Fourier transform infrared (FT-IR) demonstrated that no significant interactions occurred between the drug and excipients in Tet-NS. Powder x-ray diffraction analysis (PXRD) indicated that some of the Tet transformed into amorphous state during the preparation process. In short-term stability study, Tet-NS successfully maintained its physical stability. In summary, under the guidance of the QbD concept, this study rapidly developed Tet-NS using acoustic resonance technology, which can effectively improve the solubility and dissolution properties of Tet. During the development of Tet-NS, AR technology has demonstrated high particle size reduction capability, the ability to process multiple sets of formulations in parallel, and excellent scale-up capability. Meanwhile, the method and concept of this study are not limited to Tet, but also applicable to other poorly water-soluble drugs.

CAS / MDL: 9004-64-2
研究领域: 药学 · 纳米技术 · 药物递送系统 · 制剂科学
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