检索结果-南通市图书馆

Overcoming oral insulin delivery barriers： application of cell penetrating peptide and silica-based nanoporous composites

在线全文

学校读者我要写书评

暂无评论

Frontiers of Chemical Science and Engineering 2013年第1期7卷 9-19页

作者： Huining HE junxiao ye Jianyong SHENG Jianxin WANG Yongzhuo HUANG Guanyi CHEN Jingkang WANG Victor C YANG School of Chemical Engineering and Technology Tianjin University Tianjin 300072 China Department of Pharmaceutics School of Pharmacy Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education & PLA Shanghai 201203 China Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China School of Environmental Science and Engineering State Key Laboratory of Engines Tianjin University Tianjin 300072 China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of Pharmacy Tianjin Medical University Tianjin 300070 China Department of Pharmaceutical Sciences College of Pharmacy University of Michigan Michigan 48109-1065 USA

Oral insulin delivery has received the most attention in insulin formulations due to its high patient compliance and, more importantly, to its potential to mimic the physiologic insulin secretion seen in non-diabetic individuals. However, oral insulin delivery has two major limitations： the enzymatic barrier that leads to rapid insulin degradation, and the mucosal barrier that limits insulin＇s bioavailability. Several approaches have been actively pursued to circumvent the enzyme barrier, with some of them receiving promising results. yet, thus far there has been no major success in overcoming the mucosal barrier, which is the main cause in undercutting insulin＇s oral bioavailability. In this review of our group＇s research, an innovative silica-based, mucoadhesive oral insulin formulation with encapsulated-insulin/cell penetrating peptide （CPP） to overcome both enzyme and mucosal barriers is discussed, and the preliminary and convincing results to confirm the plausibility of this oral insulin delivery system are reviewed. In vitro studies demonstrated that the CPPinsulin conjugates could facilitate cellular uptake of insulin while keeping insulin＇s biologic functions intact. It was also confirmed that low molecular weight protamine （LMWP） behaves like a CPP peptide, with a cell translocation potency equivalent to that of the widely studied TAT. The mucoadhesive properties of the produced silica-chitosan composites could be controlled by varying both the pH and composition; the composite consisting of chitosan （25wt-%） and silica （75 wt-%） exhibited the greatest mucoadhesion at gastric pH. Furthermore, drugrelease from the composite network could also be regulated by altering the chitosan content. Overall, the universal applicability of those technologies could lead to development of a generic platform for oral delivery of many other bioactive compounds, especially for peptide or protein drugs which inevitably encounter the poor bioavailability issues.

关键词： insulin cell penetrating peptide mucoadhesive composites oral delivery

Ultrasound-mediated targeted microbubbles： a new vehicle for cancer therapy

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Frontiers of Chemical Science and Engineering 2013年第1期7卷 20-28页

作者： junxiao ye Huining HE Junbo GONG Weibing DONG Yongzhuo HUANG Jianxin WANG Guanyi CHEN Victor C YANG School of Chemical Engineering and Technology Tianjin University Tianjin 300072 China Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China Department of Pharmaceutics School of Pharmacy Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education & PLA Shanghai 201203 China School of Environmental Science and Engineering State Key Laboratory of Engines Tianjin University Tianjin 300072 China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of Pharmacy Tianjin Medical University Tianjin 300070 China Department of Pharmaceutical Sciences College of Pharmacy University of Michigan Ann Arbor MI 48109-1065 USA

With the hope of overcoming the serious side effects, great endeavor has been made in tumor-targeted chemotherapy, and various drug delivery modalities and drug carriers have been made to decrease systemic toxicity caused by chemotherapeutic agents. Scientists from home and abroad focus on the research of targeted microbubbles contrast agent, and the use of the targeted ultrasound microbubble contrast agent can carry gene drugs and so on to the target tissue, as well as mediated tumor cell apoptosis and tumor microvascular thrombosis block, etc., thus plays the role of targeted therapy. Recent studies have elucidated the mechanisms of drug release and absorption, however, much work remains to be done in order to develop a successful and optimal system. In this review, we summarized the continuing efforts in under-standing the usage of the ultrasound triggered target microbubbles in cancer therapy, from release mechanism to preparation methods. The latest applications of ultra-sound-triggered targeted microbubbles in cancer therapy, especially in gene therapy and antiangiogenic cancer therapy were discussed. Moreover, we concluded that as a new technology, ultrasound-triggered targeted microbubbles used as drug carriers and imaging agents are still energetic and are very likely to be translated into clinic in the near future.

关键词： ultrasound-mediated targeted microbubbles cancer

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

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Frontiers of Chemical Science and Engineering 2013年第4期7卷 496-507页

作者： Huining HE Qiuling LIANG Meong Cheoi SHIN Kyuri LEE Junbo GONG junxiao ye Quan LIU Jingkang WANG Victor YANG Department of Pharmaceutical Sciences College of Pharmacy University of Michigan Ann Avbor MI 48109-1065 USA Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University Tianjin 300072 China State Key Laboratory for Chemical Engineering School of Chemical Engineering and Technology Tianjin University Tianjin 300072 China

Successful development of a new drug is prohibitively expensive, and is estimated to cost approxi- mately S100-500 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 attri- butes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appro- priately 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 10^6- 10^8 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%）, reflect- ing the difficulties of utilizing these agents in clinical practice. In

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

Aptamer-coded DNA nanoparticles for targeted doxorubicin delivery using pH-sensitive spacer

在线全文

学校读者我要写书评

暂无评论

Frontiers of Chemical Science and Engineering 2017年第4期11卷 529-536页

作者： Zhang, Pengwei ye, junxiao Liu, Ergang Gong, Junbo Yang, Victor C. Sun, Lu Zhang, Jiacheng He, Huining Lee, Seung-Jin Tianjin Univ Sch Chem Engn & Technol State Key Lab Chem Engn Tianjin 300072 Peoples R China Tianjin Med Univ Tianjin Key Lab Technol Enabling Dev Clin Therape Tianjin 300072 Peoples R China Ewha Womans Univ Dept Pharm Seoul 120750 South Korea Univ Michigan Coll Pharm Dept Pharmaceut Sci 428 Church St Ann Arbor MI 48109 USA

An anticancer drug delivery system consisting of DNA nanoparticles synthesized by rolling circle amplification （RCA） was developed for prostate cancer membrane antigen （PSMA） targeted cancer therapy. The template of RCA was a DNA oligodeoxynucleotide coded with PSMA-targeted aptamer, drug-loading domain, primer binding site and pH-sensitive spacer. Anticancer drug doxorubicin, as the model drug, was loaded into the drug-loading domain （multiple GC-pair sequences） of the DNA nanoparticles by intercalation. Due to the integrated pH-sensitive spacers in the nanoparticles, in an acidic environment, the cumulative release of doxorubicin was far more than the cumulative release of the drug in the normal physiological environment. In cell uptake experi- ments, treated with doxorubicin loaded DNA nanoparti- cles, PSMA-positive C4-2 cells could take up more doxorubicin than PSMA-null PC-3 cells. The prepared DNA nanoparticles showed the potential as drug delivery system for PSMA targeting prostate cancer therapy.

关键词： aptamer DNA nanoparticles rolling circleamplification doxorubicin drug delivery pH sensitive

Improved method for synthesis of low molecular weight protamine–siRNA conjugate

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2018年第1期8卷 116-126页

作者： Zhili Yu junxiao ye Xing Pei Lu Sun Ergang Liu Jianxin Wang Yongzhuo Huang Seung Jin Lee Huining He Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical University College of Pharmacy Tsinghua University Collaborative Innovation Center of Chemical Science and Chemical Engineering and Technology Tianjin University Key Laboratory of Smart Drug Delivery Ministry of Education & PLA Department of Pharmaceutics School of Pharmacy Fudan University Ministry of Education & PLA Shanghai Institute of Materia Medica Chinese Academy of Sciences Department of Pharmacy Ewha Womans University Seodaemun-gu

RNAi technology has aroused wide public interest due to its high efficiency and specificity to treat multiple types of diseases. However, the effective delivery of siRNA remains a challenge due to its large molecular weight and strong anionic charge. Considering their remarkable functions in vivo and features that are often desired in drug delivery carriers, biomimetic systems for siRNA delivery become an effective and promising strategy. Based on this, covalent attachment of synthetic cell penetrating peptides(CPP) to siRNA has become of great interest. We developed a monomeric covalent conjugate of low molecular weight protamine(LMWP, a well-established CPP) and siRNA via a cytosol-cleavable disulfide linkage using PEG as a crosslinker. Results showed that the conjugates didn't generate coagulation, and exhibited much better RNAi potency and intracellular delivery compared with the conventional charge-complexed CPP/siRNA aggregates. Three different synthetic and purification methods were compared in order to optimize synthesis efficiency and product yield. The methodology using hetero-bifunctional NHS–PEG–OPSS as a crosslinker to synthesize LMWP–siRNA simplified the synthesis and purification process and produced the highest yield. These results pave the way towards siRNA biomimetic delivery and future clinical translation.

关键词： Cell penetrating peptide siRNA Conjugate Conjugation yield Biomimetic delivery Crosslinker

Genome-wide Association Analyses Reveal the Genetic Basis of Stigma Exsertion in Rice

在线全文

学校读者我要写书评

暂无评论

Molecular Plant 2017年第4期10卷 634-644页

作者： Hao Zhou Pingbo Li WeiboXie Saddam Hussain Yibo Li Duo Xia Hu Zhao Shengyuan Sun junxiao Chen Hong ye Jun Hou Da Zhao Guanjun Gao Qinglu Zhang Gongwei Wang Xingming Lian Jinghua Xiao Sibin Yu Xianghua Li Yuqing He National Key Laboratory of Crop Genetic Improvement and National Centre of Plant Gene Research (Wuhan) Huazhong Agricultural University Wuhan 430070China

Stigma exsertion, a key determinant of the rice mating system, greatly contributes to the application of heterosis in rice. Although a few quantitative trait loci associated with stigma exsertion have been fine map- ped or cloned, the underlying genetic architecture remains unclear. We performed a genome-wide associ- ation study on stigma exsertion and related floral traits using 6.5 million SNPs characterized in 533 diverse accessions of Oryza sativa. We identified 23 genomic loci that are significantly associated with stigma exsertion and related traits, three of which are co-localized with three major grain size genes GS3, GW5, and GW2. Further analyses indicated that these three genes affected the stigma exsertion by controlling the size and shape of the spikelet and stigma. Combinations of GS3 and GW5 largely defined the levels of stigma exsertion and related traits. Selections of these two genes resulted in specific distributions of floral traits among subpopulations of O. sativa. The low stigma exsertion combination gw5GS3 existed in half of the cultivated rice varieties; therefore, introducing the GW5gs3 combination into male sterile lines is of high potential for improving the seed production of hybrid rice.

关键词： stigma exsertion GWAS hybrid seed production floral traits grain shape rice

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

环保畜牧业与健康养殖发展探讨

福建畜牧兽医 2017年第2期39卷 14-18页

作者：叶君潇肖天放福建农林大学动物科学学院福州350002

当今,养殖业面对的环保要求越来越高,且人类社会对畜禽产品的质量也是高度关注。本文从畜牧业污染产生的危害、治理思路、控污的具体措施以及健康的养殖模式展开分析,并做出一些对未来养殖业发展的预测,旨在为环保养殖提供参考与借鉴。

关键词：养殖环保控污健康发展

在线全文

学校读者我要写书评

暂无评论

风力发电全阶段定子磁链观测器的设计

电器与能效管理技术 2017年第9期 63-66页

作者：罗俊骁王盛叶海峰鲁伟刘瑜朱义贤国网安徽省电力公司安徽合肥230061

提出一种改进型的磁链观测方法,利用全阶段定子磁链观测器进行定子磁链观测。为了验证提出理论的可行性,在1.5 MW双馈风机并网试验平台进行了风电机组并网、空载离网等试验。试验数据显示,全阶段观测器不仅能够满足正常运行观测,而且在... 详细信息

提出一种改进型的磁链观测方法,利用全阶段定子磁链观测器进行定子磁链观测。为了验证提出理论的可行性,在1.5 MW双馈风机并网试验平台进行了风电机组并网、空载离网等试验。试验数据显示,全阶段观测器不仅能够满足正常运行观测,而且在电网电压跌落等极端工况下观测准确性也能满足并网控制要求。

关键词：风力发电双PWM 变换器矢量控制磁链观测器

在线全文

学校读者我要写书评

暂无评论

拟除虫菊酯杀虫剂暴露对儿童健康的影响

环境化学 2024年第9期43卷 2905-2915页

作者：陆许诺陈俊潇叶小青浙江中医药大学医学技术与信息工程学院杭州310053

拟除虫菊酯类杀虫剂(pyrethroid insecticides,PYR)作为一种高效、低毒且易降解的广谱杀虫剂,自20世纪70年代以来广泛地应用于农林畜牧和家庭害虫防治.然而随着研究的深入,其对儿童的潜在危害也逐渐暴露.本文总结了国内外儿童因该农药... 详细信息

拟除虫菊酯类杀虫剂(pyrethroid insecticides,PYR)作为一种高效、低毒且易降解的广谱杀虫剂,自20世纪70年代以来广泛地应用于农林畜牧和家庭害虫防治.然而随着研究的深入,其对儿童的潜在危害也逐渐暴露.本文总结了国内外儿童因该农药暴露产生相关疾病的流行病学调查,发现其可能降低儿童的智力水平和行为能力,改变儿童的生长发育,及损伤机体的免疫功能;又通过分析相关动物实验及细胞实验,归纳了其对儿童神经、发育、免疫系统的影响及作用机制,为实验室深入研究提供科学依据,为临床治疗给予合理的指导,也为研发无害化杀虫剂给予参考思路.

关键词：拟除虫菊酯暴露水平神经毒性生殖毒性免疫毒性

维普期刊数据库博看期刊