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转铁蛋白修饰的载新吲哚菁绿脂质体的制备及其对乳腺癌光动力治疗作用研究

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中国药学杂志 2024年第11期59卷 1023-1031页

作者：卢雪张书贺赵艺涵金明姬高钟镐金光明延边大学附属医院超声医学科吉林延吉133000 中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室药物传输技术及新型制剂北京市重点实验室北京100050

目的制备转铁蛋白(Tf)修饰的载光敏剂新吲哚菁绿(IR820)脂质体,并对其进行表征,结合光动力治疗(PDT)乳腺癌4T1细胞及原位乳腺癌小鼠模型,为临床治疗乳腺癌提供一种新思路。方法采用薄膜分散法分别制备载IR820脂质体(IR820@Lipo)和Tf修... 详细信息

目的制备转铁蛋白(Tf)修饰的载光敏剂新吲哚菁绿(IR820)脂质体,并对其进行表征,结合光动力治疗(PDT)乳腺癌4T1细胞及原位乳腺癌小鼠模型,为临床治疗乳腺癌提供一种新思路。方法采用薄膜分散法分别制备载IR820脂质体(IR820@Lipo)和Tf修饰的载IR820脂质体(Tf-IR820@Lipo),采用紫外(UV)法检测其包封率,用透射电子显微镜和粒径仪考察其理化性质;以激光共聚焦和流式细胞技术观察4T1细胞对两者的摄取情况;CCK8实验评价两者对4T1细胞的增殖抑制;活性氧(ROS)检测在激光(Laser)照射下两者细胞内荧光强度差异;体内小动物成像法观察药物在模型小鼠内的聚集情况;体内药效学研究分析药物抗癌作用及毒副作用。结果IR820@Lipo和Tf-IR820@Lipo平均粒径分别为(84.30±15.66)、(116.20±14.68)nm,电位分别为(-8.21±2.06)、(-5.23±1.19)mV;透射电镜表征显示该脂质体呈类球形,分布均匀;IR820@Lipo的包封率为(94.61±0.67)%,载药量为(8.82±0.92)%;Tf-IR820@Lipo的包封率为(95.55±0.83)%,载药量为(8.92±1.01)%。Tf-IR820@Lipo在Laser照射下能显著抑制4T1细胞的增殖并促进其凋亡;ROS检测结果显示Tf-IR820@Lipo在Laser照射下能使4T1细胞内荧光强度明显增强;荷瘤小鼠的体内实验结果显示,Tf-IR820@Lipo光照组在小鼠体内具有较高的肿瘤靶向性;体内药效学研究显示Tf-IR820@Lipo对乳腺癌的抑制作用最强,且未造成小鼠的肝肾功能损伤,无明显的毒副作用。结论Tf-IR820@Lipo以其高靶向性、高疗效及低毒性有望成为治疗乳腺癌的新型制剂。

关键词：转铁蛋白光敏性脂质体光动力疗法乳腺癌新吲哚菁绿

The influence of the gut microbiota on the bioavailability of oral drugs

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Acta Pharmaceutica Sinica B 2021年第7期11卷 1789-1812页

作者： Xintong Zhang Ying Han Wei Huang mingji jin Zhonggao Gao State Key Laboratory of Bioactive Substance and Function of Natural Medicines Department of PharmaceuticsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Due to its safety,convenience,low cost and good compliance,oral administration attracts lots of ***,the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal *** of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs,influencing the drug transport process and altering some gastrointestinal *** this review,we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs,which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.

关键词： Gut microbiota Oral drugs Bioavailability Probiotics Colon-specific drug delivery system

Preparation of pegylated lumbrokinase and an evaluation of its thrombolytic activity both in vitro and in vivo

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Acta Pharmaceutica Sinica B 2013年第2期3卷 123-129页

作者： mingji jin Wei Chen Wei Huang Long Rong Zhonggao Gao State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing Key Laboratory of Drug Delivery Technology and Novel FormulationsInstitute of Materia MedicaChinese Academy of Medical SciencesBeijing 100050China Beijing University of Aeronautics and Astronautics Beijing 100191China

Lumbrokinase(LK)is a group of serine proteases with strong fibrinolytic and thrombolytic *** clinical practice,LK can only be administered orally because of its antigenicity,iinmunogenicity and potential to produce anaphylactic reactions after ***,many useful drugs such as interferon,insulin,erythropoietin and interleukin have been modified with polyethylene glycol(PEG)to prepare injectable *** this study,LK was modified with methoxy PEG succinimidyl carbonate(mPEG-SC)with molecular weights of 5000,10,000 and 20,000 and the pegylatcd products were isolated and purified using the Akta protein purification *** extent of pegylation was detennined by *** activities of pegylatcd and unmodified LK were measured both in vitro against urokinase on fibrin plates and in vivo using a mouse carageenan black tail *** pegylation was obtainal using mPEG-SC_(5000) in a buffer pH 8.0 with a reaction time of 5 h,reaction temperature of 0℃ and LK:mPEG-SC molar ratio of 1:*** results show that mPEG modified LK has strong fibrinolytic and thrombolytic activities both in vitro and in *** is suggested that the pegylatcd LK is a promising injectable thrombolytic agent for the treatment of thrombotic diseases in clinical practice.

关键词： Lumbrokinase Methoxy polyethylene glycol succinimidyl carbonate Pegylation Fibrinolytic activity

Multifunctional oral delivery systems for enhanced bioavailability of therapeutic peptides/proteins

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Acta Pharmaceutica Sinica B 2019年第5期9卷 902-922页

作者： Ying Han Zhonggao Gao Liqing Chen Lin Kang Wei Huang mingji jin Qiming Wang You Han Bae State Key Laboratory of Bioactive Substance and Function of Natural Medicines Department of PharmaceuticsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China Department of Pharmaceutics and Pharmaceutical Chemistry the University of UtahSalt Lake CityUT84108USA

In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability(less than 1%–2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.

关键词： Multifunctional delivery systems Oral Bioavailability Macromolecules Peptides and proteins Gastrointestinal environment Epithelial barriers Nanoparticles

Research advances in peptide-drug conjugates

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药学学报:英文版 2023年第9期13卷 3659-3677页

作者： Liming Gong Heming Zhao Yanhong Liu Hao Wu Chao Liu Shuangyan Chang Liqing Chen mingji jin Qiming Wang Zhonggao Gao Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations Department of PharmaceuticsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of Pharmacy Yanbian UniversityYanji 133000China

Peptide-drug conjugates(PDCs)are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable *** an emerging prodrug strategy,PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the *** the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs,PDCs have already been extensively applied in drug ***,we review the types and mechanisms of peptides,linkers and drugs used to construct PDCs,and summarize the clinical applications and challenges of PDC drugs.

关键词： Peptide-drug conjugates Peptides Linkers Drug delivery systems Prodrug strategy

Versatile flexible micelles integrating mucosal penetration and intestinal targeting for effectively oral delivery of paclitaxel

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3425-3443页

作者： Chao Liu Wei Liu Yanhong Liu Hongxia Duan Liqing Chen Xintong Zhang mingji jin Minhu Cui Xiuquan Quan Libin Pan Jiachun Hu Zhonggao Gao Yan Wang Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations Department of PharmaceuticsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of Histology and Embryology Chongqing Key Laboratory of NeurobiologyBrain and Intelligence Research Key Laboratory of Chongqing Education CommissionThird Military Medical UniversityChongqing 400038China Department of Gastroenterology Yanbian University HospitalYanji 133000China

The extremely low bioavailability of oral paclitaxel(PTX)mainly due to the complicated gastrointestinal environment,the obstruction of intestinal mucus layer and epithelium ***,it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles *** this work,a high-density PEGylation-based glycocholic acid-decorated micelles(PTX@GNPs)was constructed by a novel polymer,9-Fluorenylmethoxy carbonyl-poly ethylene glycocholic acid(Fmoc-PEG-GCA).The Fmoc motif in this polymer could encapsulate PTX viaπ-πstacking to form the core of micelles,and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of *** on this versatile and flexible carriers,PTX@GNPs possess mucus trapping escape ability due to the flexible PEG,and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid *** in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX,and exhibited similar antitumor efficacy to Taxol injection via intravenous *** addition,oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX,which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

关键词： Mucus penetration Oral nanoparticles Bile acids Trans-epithelium Chemotherapy Paclitaxel Bioavailability Intestineepithelium targeting

Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment

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Acta Pharmaceutica Sinica B 2015年第3期5卷 169-175页

作者： Lin Kang Zhonggao Gao Wei Huang mingji jin Qiming Wang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing City Key Laboratory of Drug Delivery Technology and Novel FormulationsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells,which is usually caused by abnormal gene *** interference mediated by si RNA and mi RNA can selectively knock down the carcinogenic genes by targeting specific m ***,combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer *** to poor stability and solubility associated with gene agents and drugs,suitable protective carriers are needed and have been widely researched for the *** this review,we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents,as well as the advances in co-delivery systems.

关键词： Nanocarrier Co-delivery Chemotherapeutic drug Gene Liposome Micelle Dendrimer Supramolecular system

脑苷肌肽在改善急性缺血性脑梗死患者神经功能及日常活动能力中的效果观察

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中国卫生标准管理 2015年第29期6卷 102-103页

作者：金明济吉林省白山市通化矿业集团公司总医院神经内科 134300

目的探讨脑苷肌肽在急性缺血性脑梗死治疗中的应用效果。方法选取患者78例,对照组在常规治疗基础上加用血栓通及奥扎格雷注射液治疗,观察组在对照组基础上加用脑苷肌肽注射液治疗。结果观察组治疗后神经功能缺损评分及日常生活活动能力... 详细信息

目的探讨脑苷肌肽在急性缺血性脑梗死治疗中的应用效果。方法选取患者78例,对照组在常规治疗基础上加用血栓通及奥扎格雷注射液治疗,观察组在对照组基础上加用脑苷肌肽注射液治疗。结果观察组治疗后神经功能缺损评分及日常生活活动能力评分改善情况优于对照组,观察组治疗有效率为92.31%,高于对照组的79.49%,对比差异具有统计学意义(P<0.05)。结论脑苷肌肽可显著改善患者神经功能及日常活动能力。

关键词：脑苷肌肽脑梗死神经功能日常活动能力

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人工湿地在农药处理领域中的应用研究

北方园艺 2016年第14期 198-201页

作者：赵静金明姬王颖延边大学理学院

在简要介绍人工湿地的概念及优缺点的基础上,从物理、化学及生物净化的角度,阐述了人工湿地对农药的去除机理及人工湿地在农药处理领域中的研究进展。同时,探讨了人工湿地在应用过程中存在的问题,对其在农药处理领域中的应用进行了研究... 详细信息

在简要介绍人工湿地的概念及优缺点的基础上,从物理、化学及生物净化的角度,阐述了人工湿地对农药的去除机理及人工湿地在农药处理领域中的研究进展。同时,探讨了人工湿地在应用过程中存在的问题,对其在农药处理领域中的应用进行了研究展望。

关键词：人工湿地农药净化机理