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Bio-mimetic drug delivery systems designed to help the senior population reconstruct melatonin plasma profiles similar to those of the healthy younger population

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Acta Pharmaceutica Sinica B 2014年第1期4卷 60-66页

作者： Ying Li Liuyi Wang Li Wu Xueju zhang Xue Li Zhen Guo Haiyan Li Peter York Shuangying Gui jiwen zhang Anhui University of Chinese Medicine Hefei 230038China Center for Drug Delivery Systems Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Hainan Weikang Pharmaceutical(Qianshan)Co. LtdAnqing 246000China College of Life Sciences Jilin UniversityChangchun 130012China

The secretion of melatonin(MT)is obviously different in the younger and the senior sectors of the population,and the maximum plasma concentration of seniors is only half of that in the younger population group.If exogenous MT can be supplied to senior citizens based on the secretion rate and amount of endogenous MT in the younger population by a bio-mimetic drug delivery system(DDS),an improved therapeutic effect and reduced side effects can be expected.Based upon this hypothesis,the pharmacokinetic parameters of MT,namely,the absorption rate constant(ka),the elimination rate constant(ke),and the ratio of absorption rate(F)to the apparent volume of distribution(V)were obtained by a residual method depending on the plasma concentration curve of immediate release preparations in the healthy younger population.The dose-division method was applied to calculate the cumulative release profiles of MT achieved by oral administration of a controlled release drug delivery system(DDS)to generate plasma MT profiles similar to the physiological level-time profiles.The in vivo release of MT deduced from the healthy younger population physiological MT profiles as the pharmacokinetic output of the bio-mimetic DDS showed a two-phase profile with two different zero order release rates,namely,4.919μg/h during 0-4 h(r=0.9992),and 11.097μg/h during 4-12 h(r=0.9886),respectively.Since the osmotic pump type of DDS generally exhibits a good correlation between in vivo and in vitro release behaviors,an osmotic pump controlled delivery system was designed in combination with dry coating technology targeting on the cumulative release characteristics to mimic the physiological MT profiles in the healthy younger population.The high similarity between the experimental drug release profiles and the theoretical profiles(similarity factor f_(2)>50)and the high correlation between the predicted plasma concentration profiles and the theoretical plasma concentration profiles(r=0.9366,0.9163,0.9264)indicated that a prototype bio-mimetic drug deliver

关键词： Bio-mimetic DDS Melatonin Dose-division method Osmotic pump Residual method

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Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery

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Acta Pharmaceutica Sinica B 2020年第9期10卷 1709-1718页

作者： Kena Zhao Tao Guo Caifen Wang Yong Zhou Ting Xiong Li Wub Xue Li Priyanka Mittal Senlin Shi Ruxandra Gref jiwen zhang College of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 311402China Center for Drug Delivery System Shanghai Institute of Materia MedicaState Key Laboratory of Drug ResearchChinese Academy of SciencesShanghai 201203China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China Key Laboratory of Modern Chinese Medicine Preparations Ministry of EducationJiangxi University of Traditional Chinese MedicineNanchang 330004China Universite´Paris-Saclay CNRS 8214Institut des Sciences Mole´culaires d’OrsayOrsay 91405France University of Chinese Academy of Sciences Beijing 100049China

It is essential to develop new carriers for laryngeal drug delivery in light of the lack of therapy in laryngeal related diseases.When the inhalable micron-sized crystals ofγ-cyclodextrin metal-organic framework(CD-MOF)was utilized as dry powder inhalers(DPIs)carrier with high fine particle fraction(FPF),it was found in this research that the encapsulation of a glycoside compound,namely,scutellarin(SCU)in CD-MOF could significantly enhance its laryngeal deposition.Firstly,SCU loading into CD-MOF was optimized by incubation.Then,a series of characterizations were carried out to elucidate the mechanisms of drug loading.Finally,the laryngeal deposition rate of CD-MOF was 57.72±2.19%improved by SCU,about two times higher than that of CD-MOF,when it was determined by Next Generation Impactor(NGI)at 65 L/min.As a proof of concept,pharyngolaryngitis therapeutic agent dexamethasone(DEX)had improved laryngeal deposition after being co-encapsulated with SCU in CDMOF.The molecular simulation demonstrated the configuration of SCU in CD-MOF and its contribution to the free energy of the SCU@CD-MOF,which defined the enhanced laryngeal anchoring.In conclusion,the glycosides-like SCU could effectively enhance the anchoring of CD-MOF particles to the larynx to facilitate the treatment of laryngeal diseases.

关键词： Laryngeal delivery g-Cyclodextrin metalorganic framework Scutellarin Dexamethasone Molecular simulation

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Synchrotron radiation-based Fourier-transform infrared spectromicroscopy for characterization of the protein/peptide distribution in single microspheres

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Acta Pharmaceutica Sinica B 2015年第3期5卷 270-276页

作者： Manli Wang Xiaolong Lu Xianzhen Yin Yajun Tong Weiwei Peng Li Wu Haiyan Li Yan Yang Jingkai Gu Tiqiao Xiao Min Chen jiwen zhang School of Pharmaceutical Sciences Anhui University of Chinese Medicine Center for Pharmaceutical Preparations Shanghai Institute of Materia MedicaChinese Academy of Sciences School of Mechanical Engineering Shanghai Institute of Technology Shanghai Synchrotron Radiation Facility Shanghai Institute of Applied PhysicsChinese Academy of Sciences College of Life Sciences Jilin University

The present study establishes a visualization method for the measurement of the distribution and localization of protein/peptide constituents within a single poly-lactide-co-glycolide(PLGA) microsphere using synchrotron radiation–based Fourier-transform infrared spectromicroscopy(SR-FTIR).The representative infrared wavenumbers specific for protein/peptide(Exenatide) and excipient(PLGA) were identified and chemical maps at the single microsphere level were generated by measuring and plotting the intensity of these specific bands.For quantitative analysis of the distribution within microspheres,Matlab software was used to transform the map file into a 3D matrix and the matrix values specific for the drug and excipient were extracted.Comparison of the normalized SR-FTIR maps of PLGA and Exenatide indicated that PLGA was uniformly distributed,while Exenatide was relatively non-uniformly distributed in the microspheres.In conclusion,SR-FTIR is a rapid,nondestructive and sensitive detection technology to provide the distribution of chemical constituents and functional groups in microparticles and microspheres.

关键词： Fourier-transform infrared spectromicroscopy Protein distribution Microsphere Exenatide PLGA

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Optimization of taste-masking on ibuprofen microspheres with selected structure features

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Asian Journal of Pharmaceutical Sciences 2019年第2期14卷 174-182页

作者： Wei Qin Yuanzhi He Zhen Guo Liu zhang Li Wu Xianzhen Yin Shailendra Shakya Abi Maharjan Yan Tang Weifeng Zhu jiwen zhang Ministry of Education Jiangxi University of Traditional Chinese Medicine Shanghai Institute of Materia Medica Chinese Academy of Sciences School of Pharmacy Shenyang Pharmaceutical University School of Pharmacy University of Chinese Academy of Sciences

The microsphere was a primary particulate system for taste-masking with unique structural features defined by production process. In this article, ibuprofen lipid microspheres of octadecanol and glycerin monostearate were prepared to mask the undesirable taste of ibuprofen via three kinds of spray congealing processes, namely, air-cooling, water-cooling and citric acid solution-cooling. The stereoscopic and internal structures of ibuprofen microspheres were quantitatively analyzed by synchrotron radiation X-ray micro-computed tomography(SR-μCT) to establish the relationship between the preparation process and microsphere architectures. It was found that the microstructure and morphology of the microspheres were significantly influenced by preparation processes as the primary factors to determine the release profiles and taste-masking effects. The sphericity of ibuprofen microspheres congealed in citric acid solution was higher than that of other two and its morphology was more regular than that being congealed in air or distilled water, and the contact angles between congealing media and melted ibuprofen in octadecanol and glycerin monostearate well demonstrated the structure differences among microspheres of three processes which controlled the release characteristics of the microspheres. The structure parameters like porosity, sphericity, and radius ratio from quantitative analysis were correlated well with drug release behaviors. The results demonstrated that the exterior morphology and internal structure of microspheres had considerable influences on the drug release behaviors as well as taste-masking effects.

关键词： Ibuprofen microsphere Spray congealing Internal structure Synchrotron radiation X-ray micro-computed tomography

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Three dimensional distribution of surfactant in microspheres revealed by synchrotron radiation X-ray microcomputed tomography

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Asian Journal of Pharmaceutical Sciences 2017年第4期12卷 326-334页

作者： Li Wu Manli Wang Vikramjeet Singh Haiyan Li Zhen Guo Shuangying Gui Peter York Tiqiao Xiao Xianzhen Yin jiwen zhang Center for Drug Delivery Systems Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201210China School of Pharmaceutical Sciences Anhui University of Chinese MedicineHefei 230038China Institute of Pharmaceutical Innovation University of BradfordBradfordWest Yorkshire BD7 1DPUnited Kingdom Shanghai Synchrotron Radiation Facility Shanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai 201204China

This study investigated the formulation mechanism of microspheres via internal surfactant distribution. Eudragit L100 based microspheres loaded with bovine serum albumin were prepared by solid in oil in oil emulsion solvent evaporation method using acetone and liquid paraffin system containing sucrose stearate as a surfactant. The fabricated microspheres were evaluated for encapsulation efficiency, particle size, production yield, and in vitro release characteristics. The internal structures of microspheres were characterized using synchrotron radiation X-ray microcomputed tomography(SR-μCT). The enhanced contrast made the sucrose stearate distinguished from Eudragit to have its three dimensional(3D) distribution. Results indicated that the content and concentration determined the state of sucrose stearate and had significant influences on the release kinetics of protein. The dispersity of sucrose stearate was the primary factor that controlled the structure of the microspheres and further affected the encapsulation efficiency, effective drug loading, as well as in vitro release behavior. In conclusion, the 3D internal distribution of surfactant in microspheres and its effects on protein release behaviors have been revealed for the first time. The highly resolved 3D architecture provides new evidence for the deep understanding of the microsphere formation mechanism.

关键词： Three dimensional Synchrotron radiation X-ray microcomputed tomography Distribution Microsphere Sucrose stearate

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安徽淮南舜耕山地质遗迹资源类型及特征

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高校地质学报 2024年第1期30卷 89-99页

作者：张子康顾承串吴基文赵铭詹润邵晴晴张缘缘安徽理工大学地球与环境学院淮南232001 安徽省煤田地质局勘查研究院合肥230088

安徽淮南舜耕山位于华北克拉通淮南煤田南缘逆冲推覆构造带,天然出露与人工剥露地质遗迹数量众多,系统地查明地质遗迹资源类型、分布及特征可为区域地质对比研究以及地学科普与旅游规划工作奠定重要基础。文章通过野外地质调查,共发现... 详细信息

安徽淮南舜耕山位于华北克拉通淮南煤田南缘逆冲推覆构造带,天然出露与人工剥露地质遗迹数量众多,系统地查明地质遗迹资源类型、分布及特征可为区域地质对比研究以及地学科普与旅游规划工作奠定重要基础。文章通过野外地质调查,共发现舜耕山主要地质遗迹点62处,可划分为3大类、8类、14亚类,其中以华北型寒武系—奥陶系典型剖面、碳酸盐岩地貌、断裂构造以及矿业遗址等地质遗迹景观尤为发育,具有极高的科研和观赏价值;结合前人研究资料,初步讨论了舜耕山地质遗迹成因及其区域地质背景,为舜耕山地质遗迹资源开发提供理论依据;针对舜耕山在地质遗迹资源保护与开发利用存在的问题,提出对应的远景规划和建议。

关键词：地质遗迹成因分类地质背景地学科普舜耕山

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Metal-organic frameworks for advanced drug delivery

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2362-2395页

作者： Siyu He Li Wu Xue Li Hongyu Sun Ting Xiong Jie Liu Chengxi Huang Huipeng Xu Huimin Sun Weidong Chen Ruxandra Gref jiwen zhang Center for Drug Delivery Systems Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Institut de Sciences Moléculaires D'Orsay UniversitéParis-SaclayOrsay Cedex 91400France Key Laboratory of Modern Chinese Medicine Preparations Ministry of EducationJiangxi University of Traditional Chinese MedicineNanchang 330004China School of Pharmaceutical Sciences Anhui University of Chinese MedicineHefei 230012China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China

Metal-organic frameworks(MOFs),comprised of organic ligands and metal ions/metal clusters via coordinative bonds are highly porous,crystalline materials.Their tunable porosity,chemical composition,size and shape,and easy surface functionalization make this large family more and more popular for drug delivery.There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications.This article presents an overall review and perspectives of MOFs-based drug delivery systems(DDSs),starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands.Then,the synthesis and characterization of MOFs for DDSs are developed,followed by the drug loading strategies,applications,biopharmaceutics and quality control.Importantly,a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics,diseases therapy and advanced DDSs.In particular,the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed.Finally,challenges in MOFs development for DDSs are discussed,such as biostability,biosafety,biopharmaceutics and nomenclature.

关键词： Metal-organic frameworks Drug loading Drug delivery systems Synthesis and characterization Diseases therapy Pharmaceutics Biopharmaceutics Biosafety

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A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs

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Science China(Life Sciences) 2020年第5期63卷 623-634页

作者： Weiye Chen Dongming Zhao Xijun He Renqiang Liu Zilong Wang Xianfeng zhang Fang Li Dan Shan Hefeng Chen jiwen zhang Lulu Wang Zhiyuan Wen Xijun Wang Yuntao Guan Jinxiong Liu Zhigao Bu State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150001China National High Containment Laboratory for Animal Diseases Control and Prevention Harbin 150069China

African swine fever(ASF)is a devastating infectious disease in swine that is severely threatening the global pig industry.An efficacious vaccine is urgently required.Here,we used the Chinese ASFV HLJ/18 as a backbone and generated a series of genedeleted viruses.The virulence,immunogenicity,safety,and protective efficacy evaluation in specific-pathogen-free pigs,commercial pigs,and pregnant sows indicated that one virus,namely HLJ/18-7GD,which has seven genes deleted,is fully attenuated in pigs,cannot convert to the virulent strain,and provides complete protection of pigs against lethal ASFV challenge.Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV,and as such is expected to play an important role in controlling the spread of ASFV.

关键词： African swine fever vaccine safety protective efficacy pig

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酒石酸布托啡诺预防妇科手术患者苏醒期躁动的合理给药时机探讨

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甘肃医药 2024年第2期43卷 140-142页

作者：张望张继青梁吉文兰州市第二人民医院甘肃兰州730046

目的:比较不同时间给予布托啡诺预防妇科手术患者苏醒期躁动的疗效。方法:选取2020年4月至2021年9月兰州市第二人民医院择期行腹腔镜子宫肌瘤剔除术患者60例,分为三组,各20例。B1组诱导前静注布托啡诺0.02 mg/kg,B2组术毕前30min静注布... 详细信息

目的:比较不同时间给予布托啡诺预防妇科手术患者苏醒期躁动的疗效。方法:选取2020年4月至2021年9月兰州市第二人民医院择期行腹腔镜子宫肌瘤剔除术患者60例,分为三组,各20例。B1组诱导前静注布托啡诺0.02 mg/kg,B2组术毕前30min静注布托啡诺0.02 mg/kg,C组空白对照。记录患者拔管前(T0),拔管即刻(T1)、拔管后5分钟(T2)、拔管后30分钟(T3)的MAP、HR;拔管时间;拔管时的躁动评分(RS评分);拔管后30 min时的Ramsay镇静评分;麻醉恢复室停留时间(PACU),并进行比较。结果:与C组比较,B1组、B2组患者各时点(T0~T3)MAP、HR降低(P0.05);三组患者拔管时间差异无统计学意义(P>0.05);拔管时的RS评分B1组、B2组均较C组低(P0.05),拔管后15 min的Ramsay评分B1、B2组较C组高(P0.05)。结论:布托啡诺可用于预防妇科手术患者苏醒期躁动,且麻醉诱导前给药效果优于手术结束前30 min给药。

关键词：酒石酸布托啡诺妇科手术苏醒期躁动给药时机

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硬式内窥镜检测仪评估硬式内窥镜光学性能的研究

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中国医学装备 2024年第2期21卷 33-36页

作者：颜培巧张伟张继文国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院消毒供应中心北京100021 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院护理部北京100021

目的:应用硬式内窥镜检测仪检测法和目测检测法检测评估硬式内窥镜的导光性能和成像性能,探讨硬式内窥镜检测仪检测硬式内窥镜光学性能的应用效果。方法:选取2022年5月至2023年5月北京协和医学院肿瘤医院膀胱镜手术使用的174件硬式内窥... 详细信息

目的:应用硬式内窥镜检测仪检测法和目测检测法检测评估硬式内窥镜的导光性能和成像性能,探讨硬式内窥镜检测仪检测硬式内窥镜光学性能的应用效果。方法:选取2022年5月至2023年5月北京协和医学院肿瘤医院膀胱镜手术使用的174件硬式内窥镜,分别采用目测法和检测仪法对174件硬式内窥镜进行清洗消毒后的检测。根据检测方式不同,将其分为目测组(90件)和检测仪组(84件)。对比分析两种检测硬式内窥镜导光性能和成像性能的方法,比较两种检测方法的检测效果。结果:检测仪组和目测组光通量不合格检出率分别为11.9%(10/84)和0(0/90),两组硬式内窥镜导光性能的光通量检测比较,差异有统计学意义(x^(2)=9.276,P<0.05)。硬式内窥镜成像性能检测中检测仪组和目测组的成像质量不合格检出率分别为9.5%(8/84)和1.11%(1/90),两组比较差异有统计学意义(x^(2)=6.269,P<0.05)。结论:应用硬式内窥镜检测仪可提高消毒供应中心工作人员检测硬式内窥镜光学性能的准确率,完善硬式内窥镜的质控管理,降低硬式内窥镜损耗率,延长硬式内窥镜的使用寿命,为临床提供更加安全有效的医疗器械,保障医疗安全。

关键词：硬式内窥镜检测光学性能成像性能导光性能

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