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Significance and strategies in developing delivery systems for bio-macromolecular drugs

Huining HE, Qiuling LIANG, Meong Cheol SHIN, Kyuri LEE, Junbo GONG, Junxiao YE, Quan LIU, Jingkang WANG, Victor YANG

《化学科学与工程前沿（英文）》 2013年 第7卷 第4期   页码 496-507 doi: 10.1007/s11705-013-1362-1

摘要： Successful development of a new drug is prohibitively expensive, and is estimated to cost approximately $100–500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attributes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appropriately designed drug delivery system (DDS) is able to overcome such limitations, and yet the cost of developing a novel drug delivery system is less than 10% of that of developing a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of developing new drugs in the past to a combined mode of developing both new drugs and innovative drug delivery systems in this century. Hence, for developing countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug. Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug (e.g., protein toxins, gene products, etc.) is equivalent to about 10 –10 of that from a conventional small molecule anti-cancer agent (e.g., doxorubicin). Hence, bio-macromolecular drugs have been recognized around the world as the future “drug-of-choice”. Yet, among the>10000 drugs that are currently available, only ~150 of them belong to these bio-macromolecular drugs (an exceedingly low 1.2%), reflecting the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these bio-macromolecular drugs are two-fold: (1) the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and (2) the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collectively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on developing delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential.

关键词： delivery systems     bio-macromolecular drugs     cell penetrating peptides    

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Developing macromolecular therapeutics: the future drug-of-choice

Huining HE, Victor C. YANG, Weibing DONG, Junbo GONG, Jingkang WANG,

《化学科学与工程前沿（英文）》 2010年 第4卷 第1期   页码 10-17 doi: 10.1007/s11705-009-0291-5

摘要： Macromolecular drugs including peptides, proteins, antibodies, polysaccharides and nucleic acids have been widely used for therapy of major diseases such as carcinoma and AIDS as well as cardiovascular and neurodegenerative disorders among other medical conditions. Due to their unmatched properties of high selectivity and efficiency, macromolecular drugs have been recognized as the drug-of-choice of the future. Since worldwide progress on macromolecular therapeutics still remains in the infant stage and is therefore wide open for equal-ground competition, R&D related to macromolecular drugs should be considered as the main point of focus in China in setting up its strategic plans in pharmaceutical development. In this article, research strategies and drug delivery approaches that should be adopted to enhance the therapeutic effects of macromolecular drugs are reviewed. In addition, comments concerning how to implement such strategies to excel from competition in this challenging research field, such as the design of innovative and highly effective delivery systems of macromolecular drugs with self-owned intellectual property rights, are provided.

关键词： worldwide     challenging     effective     macromolecular     self-owned intellectual    

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Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin, Jiandong Jiang

《医学前沿（英文）》 2021年 第15卷 第3期   页码 404-415 doi: 10.1007/s11684-021-0834-9

摘要： Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain–Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.

关键词： Zika virus     clinical drugs     ZIKV inhibitors     antivirals     repurposing    

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Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

《医学前沿（英文）》 doi: 10.1007/s11684-023-1037-3

摘要： The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir–ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir–ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir–ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China’s homegrown anti-COVID-19 drugs.

关键词： COVID-19     antiviral drugs     mindeudesivir    

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Synthesis and characterization of macromolecular surface modifier PP--PEG for polypropylene

CHEN Hanjia, SHI Xuhua, ZHU Yafei, ZHANG Yi, XU Jiarui

《化学科学与工程前沿（英文）》 2008年 第2卷 第1期   页码 102-108 doi: 10.1007/s11705-008-0018-z

摘要： A novel macromolecular surface modifier, polypropylene-grafted-poly(ethylene glycol) copolymer (PP--PEG), was synthesized by coupling polypropylene containing maleic anhydride with monohydroxyl-terminated poly(ethylene glycol). The effects of the reaction condition on the graft reactions were studied. The copolymers were characterized by IR, H NMR, thermogravimetry (TG) and differential scanning calorimetry (DSC). The results indicated that the graft reactions were hindered by increasing the molecular weight of PP or PEG. The graft copolymer was found to have a higher initial thermal degradation temperature and lower crystallization capacity as compared with pure PP, and the side chain of PEG hindered the PP chain from forming a perfect ? crystal. The thermal stability of PP--PEG decreased with the increasing content or molecular weight of PEG. The copolymers were blended with polypropylene to modify the surface hydrophilicity of the products. The results of attenuated total reflectance FTIR spectroscopy (ATR-FTIR) showed that PP--PEG could diffuse preferably onto the surface of the blends and be suitable as an effectual macromolecular surface modifier for PP.

关键词： polypropylene     crystallization capacity     attenuated     hydrophilicity     reflectance    

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Occurrence, distribution and risk assessment of abused drugs and their metabolites in a typical urban

Peng Hu, Changsheng Guo, Yan Zhang, Jiapei Lv, Yuan Zhang, Jian Xu

《环境科学与工程前沿（英文）》 2019年 第13卷 第4期 doi: 10.1007/s11783-019-1140-5

摘要：

We developed a method for determining 11 abused drugs in water and sediment.

METH and EPH were the dominant drugs in water and sediment in Beiyunhe River.

Abuse drugs in Beiyunhe River were mainly from hospitals and sewage effluents.

Abused drugs in the water would not impair the aquatic ecosystem biologically.

关键词： Drugs of abuse     Occurrence     Distribution     Urban river     Environmental risk    

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Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

《医学前沿（英文）》 2022年 第16卷 第5期   页码 815-826 doi: 10.1007/s11684-021-0891-0

摘要： Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma (BCL) due to their reliable efficacy, manageable safety, high accessibility, and convenience for use. Still, no guidelines or consensus focusing on oral drug therapies for BCL is available. To provide a reference of oral agent-based treatment for mature BCL, a panel of experts from the Lymphocyte Disease Group, Chinese Society of Hematology, Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese BCL patients on the basis of the current application status of oral drugs in China, combined with the latest authoritative guidelines in the world and current research reports. This consensus reviewed the application of oral drugs in the treatment of BCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive BCL patients. With the deepening of research and the development of standardized clinical applications, oral medications will bring better treatment to BCL patients, enabling more patients to benefit from them.

关键词： B-cell lymphoma     oral drug     targeted therapy     immunotherapy     COVID-19 pandemic    

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Surgical robotics: A look-back of latest advancement and bio-inspired ways to tackle existing challenges

Yang LIU, Jing LIU

《机械工程前沿（英文）》 2012年 第7卷 第4期   页码 376-384 doi: 10.1007/s11465-012-0352-1

摘要：

This article is dedicated to present a review on existing challenges and latest developments in surgical robotics in attempts to overcome the obstacles lying behind. Rather than to perform an exhaustive evaluation, we would emphasize more on the new insight by digesting the emerging bio-inspired surgical technologies with potentials to revolutionize the field. Typical approaches, possible applications, advantages and technical challenges were discussed. Evolutions of surgical robotics and future trends were analyzed. It can be found that, the major difficulties in the field of surgical robots may not be properly addressed by only using conventional approaches. As an alternative, bio-inspired methods or materials may shed light on new innovations. While endeavors to deal with existing strategies still need to be made, attentions should be paid to also borrow ideas from nature.

关键词： minimally invasive surgery     surgical robotics     haptic feedback     miniaturization     bio-inspiration     bionics    

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Bio-based Technologies for Resource Recovery

Aijie Wang, David Stuckey

《环境科学与工程前沿（英文）》 2018年 第12卷 第4期 doi: 10.1007/s11783-018-1079-y

摘要：

关键词： valign=     top     class=     J_zhaiyao    

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Combustion characteristics and kinetics of bio-oil

Ruixia ZHANG, Zhaoping ZHONG, Yaji HUANG

《化学科学与工程前沿（英文）》 2009年 第3卷 第2期   页码 119-124 doi: 10.1007/s11705-009-0068-x

摘要： The combustion characteristics of bio-oils derived from rice husk and corn were studied by thermogravimetry analysis. According to the thermogravimetry (TG), differential thermogravimetry (DTG) and differential thermal analysis (DTA) curves of bio-oils in air and nitrogen atmosphere, we analyzed the combustion characteristics of different kinds of bio-oils in different atmospheres and worked out the combustion kinetics parameters of the bio-oil, providing reliable base data for the burning of bio-oil. The thermogravimetry indicated that the combustion process of bio-oil was divided into three stages. At the same time, the combustion process can be described by different order reaction models, and with the method of Coats-Redfern, the activation energy and frequency factor of different kinds of bio-oils were obtained.

关键词： bio-oil     combustion characteristics     combustion kinetics    

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生物柴油技术进展与产业前景

冀星,郗小林,孔林河,李俊峰,李丽

《中国工程科学》 2002年 第4卷 第9期   页码 86-93

摘要：

综述了世界各国生物柴油技术的研究、应用及产业发展状况，分析了生物柴油制备、应用中存在的 问题，论述了发展生物柴油产业对我国石油安全、国民经济建设以及对农业产业结构调整的贡献和生物柴油对 环境的作用及可能造成的冲击，展望了该产业的发展前景，对该产业的发展提出了建议。

关键词： 生物柴油     生物柴油制备     生物柴油产业    

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nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic acid drugs

Vaibhav Mundra, Ram I. Mahato

《化学科学与工程前沿（英文）》 2014年 第8卷 第4期   页码 387-404 doi: 10.1007/s11705-014-1457-3

摘要： There are many challenges in developing efficient and target specific delivery systems of small molecule and nucleic acid drugs. Cell membrane presents one of the major barriers for the penetration of hydrophilic macromolecules across the plasma membrane. Nanocarriers have been designed to enhance their cellular uptake via endocytosis but following their cellular uptake, endosomal escape is the rate limiting step which restricts the value associated with the enhanced uptake by nanocarriers. Viruses are an excellent model for efficient cytosolic delivery by nanocarriers. Viruses exploit intracellular cues to release the genome to cytosol. In this review, we first discuss different endocytic uptake pathways and endosomal escape mechanisms. We then summarize the existing tools for studying the intracellular trafficking of nanocarriers. Finally, we highlight the important design elements of recent virus-based nanocarriers for efficient cellular uptake and endosomal escape.

关键词： nanocarrier     cellular uptake     endosomal release     nucleic acid drug    

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Production of renewable fuels by blending bio-oil with alcohols and upgrading under supercritical conditions

Sainab Omar, Suzanne Alsamaq, Yang Yang, Jiawei Wang

《化学科学与工程前沿（英文）》 2019年 第13卷 第4期   页码 702-717 doi: 10.1007/s11705-019-1861-9

摘要： The work studied a non-catalytic upgrading of fast pyrolysis bio-oil by blending under supercritical conditions using methanol, ethanol and isopropanol as solvent and hydrogen donor. Characterisation of the bio-oil and the upgraded bio-oils was carried out including moisture content, elemental content, pH, heating value, gas chromatography-mass spectrometry (GCMS), Fourier transform infrared radiation, C nuclear magnetic resonance spectroscopy, and thermogravimetric analysis to evaluate the effects of blending and supercritical reactions. The GCMS analysis indicated that the supercritical methanol reaction removed the acids in the bio-oil consequently the pH increased from 2.39 in the crude bio-oil to 4.04 after the supercritical methanol reaction. The ester contents increased by 87.49% after the supercritical methanol reaction indicating ester formation could be the major deacidification mechanism for reducing the acidity of the bio-oil and improving its pH value. Simply blending crude bio-oil with isopropanol was effective in increasing the C and H content, reducing the O content and increasing the heating value to 27.55 from 17.51 MJ·kg in the crude bio-oil. After the supercritical isopropanol reaction, the heating value of the liquid product slightly further increased to 28.85 MJ·kg .

关键词： bio-oil     blending     supercritical     upgrading     characterisation    

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volatile organic sulfur compounds in off-gas mixture from a wastewater treatment plant using a two-stage bio-trickling

Shihao Sun, Tipei Jia, Kaiqi Chen, Yongzhen Peng, Liang Zhang

《环境科学与工程前沿（英文）》 2019年 第13卷 第4期 doi: 10.1007/s11783-019-1148-x

摘要：

A two-stage BTF system was established treating odorous off-gas mixture from a WWTP.

The two-stage BTF system showed resistance for the lifting load of H2S and VOSC.

Miseq Illumina sequencing showed separated functional microbial community in BTFs.

Avoiding H2S inhibition and enhancement of VOSC degradation was achieved.

Key control point was discussed to help industrial application of the system.

关键词： Odor     Two-stage bio-trickling filter process     Bio-trickling filter     Hydrogen sulfide     Volatile organic sulfur compound    

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A review on catalytic & non-catalytic bio-oil upgrading in supercritical fluids

Sainab Omar, Yang Yang, Jiawei Wang

《化学科学与工程前沿（英文）》 2021年 第15卷 第1期   页码 4-17 doi: 10.1007/s11705-020-1933-x

摘要： This review article summarizes the key published research on the topic of bio-oil upgrading using catalytic and non-catalytic supercritical fluid (SCF) conditions. The precious metal catalysts Pd, Ru and Pt on various supports are frequently chosen for catalytic bio-oil upgrading in SCFs. This is reportedly due to their favourable catalytic activity during the process including hydrotreating, hydrocracking, and esterification, which leads to improvements in liquid yield, heating value, and pH of the upgraded bio-oil. Due to the costs associated with precious metal catalysts, some researchers have opted for non-precious metal catalysts such as acidic HZSM-5 which can promote esterification in supercritical ethanol. On the other hand, SCFs have been effectively used to upgrade crude bio-oil without a catalyst. Supercritical methanol, ethanol, and water are most commonly used and demonstrate catalyst like activities such as facilitating esterification reactions and reducing solid yield by alcoholysis and hydrolysis, respectively.

关键词： bio-oil     upgrading     supercritical     review    

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标题 作者 时间 类型 操作

Significance and strategies in developing delivery systems for bio-macromolecular drugs

Huining HE, Qiuling LIANG, Meong Cheol SHIN, Kyuri LEE, Junbo GONG, Junxiao YE, Quan LIU, Jingkang WANG, Victor YANG

期刊论文

Developing macromolecular therapeutics: the future drug-of-choice

Huining HE, Victor C. YANG, Weibing DONG, Junbo GONG, Jingkang WANG,

期刊论文

Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin, Jiandong Jiang

期刊论文

Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

期刊论文

Synthesis and characterization of macromolecular surface modifier PP--PEG for polypropylene

CHEN Hanjia, SHI Xuhua, ZHU Yafei, ZHANG Yi, XU Jiarui

期刊论文

Occurrence, distribution and risk assessment of abused drugs and their metabolites in a typical urban

Peng Hu, Changsheng Guo, Yan Zhang, Jiapei Lv, Yuan Zhang, Jian Xu

期刊论文

Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

期刊论文

Surgical robotics: A look-back of latest advancement and bio-inspired ways to tackle existing challenges

Yang LIU, Jing LIU

期刊论文

Bio-based Technologies for Resource Recovery

Aijie Wang, David Stuckey

期刊论文

Combustion characteristics and kinetics of bio-oil

Ruixia ZHANG, Zhaoping ZHONG, Yaji HUANG

期刊论文

生物柴油技术进展与产业前景

冀星,郗小林,孔林河,李俊峰,李丽

期刊论文

nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic acid drugs

Vaibhav Mundra, Ram I. Mahato

期刊论文

Production of renewable fuels by blending bio-oil with alcohols and upgrading under supercritical conditions

Sainab Omar, Suzanne Alsamaq, Yang Yang, Jiawei Wang

期刊论文

volatile organic sulfur compounds in off-gas mixture from a wastewater treatment plant using a two-stage bio-trickling

Shihao Sun, Tipei Jia, Kaiqi Chen, Yongzhen Peng, Liang Zhang

期刊论文

A review on catalytic & non-catalytic bio-oil upgrading in supercritical fluids

Sainab Omar, Yang Yang, Jiawei Wang

期刊论文