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Acta Pharmaceutica Sinica B 2024年第1期14卷 365-377页

作者： Dandan Ling Xueli Jia Ke Wang Qiucheng Yan Bochuan Yuan Lina Du Miao Li yiguang jin Anhui Medical University Hefei 230032China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer,although it is limited by the low tumor delivery efficacy of anticancer *** therapy is emerging for cancer treatment due to its high immune stimulation effect;however,excessively generated immunogenicity will cause serious inflammatory response ***,we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts(LP@BG@CCM)by layer-by-layer encapsulation for the treatment of metastatic lung *** preparation processes were simple,only involving film formation,electroporation,and pore ***@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer *** the 4T1 breast cancer metastatic lung cancer mouse models,the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance,the reduced lung weight,the clear lung tissue structure,and the enhanced cancer cell apoptosis compared to its ***,several major immune factors were improved after administration of LP@BG@CCM,including the CD4^(+)/CD8a^(+)T cells in the spleen and the TNF-α,IFN-γ,and IL-4 in the ***@BG@CCM exhibits the optimal synergistic chemo-immunotherapy,which is a promising medication for the treatment of metastatic lung cancer.

关键词： Apoptosis Bacterial ghost Cancer cell membrane Immune stimulation Liposome Lung targeting Metastatic lung cancer Paclitaxel

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可穿戴设备在药物递送中的研究进展

材料工程 2024年第8期52卷 76-86页

作者：房东阳金义光军事科学院军事医学研究院北京100850

可穿戴设备具有良好的便携性和隐蔽性,可在人体穿戴后实现预设功能。药物递送指将药物通过合适载体或技术以一定方式和规律运输到患者体内产生治疗作用,可提高药物的稳定性与生物利用度。将可穿戴设备与药物递送相结合,可实现根据患者... 详细信息

可穿戴设备具有良好的便携性和隐蔽性,可在人体穿戴后实现预设功能。药物递送指将药物通过合适载体或技术以一定方式和规律运输到患者体内产生治疗作用,可提高药物的稳定性与生物利用度。将可穿戴设备与药物递送相结合,可实现根据患者疾病信号或人为指令的释药,以及对患者体内药物浓度的监控,取代对医生和医院的依赖,获得最佳疾病治疗时机和治疗效果。可穿戴药物递送系统可直接佩戴在体表,具有无创和自行给药的特点。微针皮肤贴片、伤口愈合贴片、智能隐形眼镜等是最常见的可穿戴药物递送系统。本文对近5年可穿戴设备在治疗糖尿病、伤口愈合、眼部疾病和癌症等疾病和药物递送中的最新研究进展进行了综述,对可穿戴药物递送系统发展面临的问题和挑战进行了简单总结,并对其发展方向进行了展望。

关键词：可穿戴设备微针糖尿病癌症药物递送

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Inhalable oridonin-loaded poly(lactic-co-glycolic)acid large porous microparticles for in situ treatment of primary non-small cell lung cancer

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Acta Pharmaceutica Sinica B 2017年第1期7卷 80-90页

作者： Lifei Zhu Miao Li Xiaoyan Liu Lina Du yiguang jin Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine Anhui Medical University Department of Pharmacy Yangpu HospitalTongji University School of Medicine

Non-small cell lung cancer(NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic-co-glycolic)acid(PLGA) large porous microparticle(LPMP) for in situ treatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of 10 mm, the aerodynamic diameter of the spheres was only 2.72 mm, leading to highly efficient lung deposition. In vitro studies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPs via airway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGALPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations for in situ treatment of lung cancer.

关键词： Large porous microparticle Non-small cell lung cancer Oridonin Poly(lactic-co-glycolic) acid Pulmonary delivery

Chemo-photothermal immunotherapy for eradication of orthotopic tumors and inhibition of metastasis by intratumoral injection of polydopamine versatile hydrogels

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1447-1459页

作者： Bo Zhuang Ting Chen Yueqi Huang Zhimei Xiao yiguang jin Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Department of Chemical Defense Institute of NBC DefenseBeijing 102205China

Cancer remains one of the leading causes of death globally and metastasis always leads to treatment ***,we develop a versatile hydrogel loading photothermal agents,chemotherapeutics,and immune-adjuvants to eradicate orthotopic tumors and inhibit metastasis by combinational *** networks were synthesized via the thiol-Michael addition of polydopamine(PDA)with thiolated hyaluronic *** acted as a cross-linking agent and endowed the hydrogel with excellent photothermal ***,a chemotherapeutic agent,doxorubicin(DOX),was loaded in the hydrogel viaπ-πstacking with PDA and an immune-adjuvant,CpG-ODN,was loaded via electrostatic *** release of DOX from the hydrogel was initially slow but accelerated due to near infrared light *** hydrogels showed remarkably synergistic effect against 4T1 cancer cells and stimulated plenty of cytokines secreting from RAW264.7 ***,the hydrogels eradicated orthotopic murine breast cancer xenografts and strongly inhibited metastasis after intratumoral injection and light *** high anticancer efficiency of this chemo-photothermal immunotherapy resulted from the strong synergistic effect of the versatile hydrogels,including the evoked host immune *** combinational strategy of chemo-photothermal immunotherapy is promising for highly effective treatment of breast cancer.

关键词： Breast cancer Polydopamine Hydrogel Intratumoral injection Photothermal Chemotherapy Immunotherapy Metastasis

Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

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Acta Pharmaceutica Sinica B 2018年第3期8卷 440-448页

作者： Tongtong Zhang Yanming Chen Yuanyuan Ge Yuzhen Hu Miao Li yiguang jin Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine Anhui Medical University China Pharmaceutical University

Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler(LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.

关键词： Curcumin Dry powder inhaler Liposome Primary lung cancer Pulmonary delivery

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3D打印多功能敷料治疗放创复合伤

中国组织工程研究 2024年第10期28卷 1562-1567页

作者：焦文成代晶严文锐沈锦涛胡静璐金义光杜丽娜河北大学河北省保定市071002 中国人民解放军军事医学研究院辐射医学研究所北京市100850 中国人民解放军西部战区总医院四川省成都市610083 广东药科大学广东省广州市510006 河南大学河南省开封市475004

背景:放创复合伤主要发生在肿瘤放疗和核辐射事故患者中,由于辐射破坏修复机制导致伤口愈合延迟或延长,目前仍缺乏有效的治疗策略。目的:针对放创复合伤的多种临床症状,制备抗菌、加速愈合和局部麻醉的多功能敷料。方法:以左氧氟沙星、... 详细信息

背景:放创复合伤主要发生在肿瘤放疗和核辐射事故患者中,由于辐射破坏修复机制导致伤口愈合延迟或延长,目前仍缺乏有效的治疗策略。目的:针对放创复合伤的多种临床症状,制备抗菌、加速愈合和局部麻醉的多功能敷料。方法:以左氧氟沙星、丝素蛋白和盐酸利多卡因为原料,应用3D生物打印技术制备多功能创面敷料。①将多功能敷料分别放置于表面涂有金黄色葡萄球菌、大肠杆菌与铜绿假单胞菌的固定培养板上,37℃孵育过夜,检测抑菌圈直径。②将40只昆明种小鼠随机分单纯创伤组、放创模型组、治疗组、阳性药组,每组10只。放创模型组、治疗组、阳性药组小鼠全身接受60Coγ射线照射,辐射1 h后,在4组小鼠背部各制作1个直径1 cm的全层皮肤缺损创面,单纯创伤组、放创模型组创面涂抹生理盐水,阳性药组创面涂抹三乙醇胺乳膏,治疗组创面覆盖多功能敷料,每隔1 d更换敷料或换药,连续治疗14 d。创面造模后3,7,14 d,检测创面愈合率与血清白细胞介素6水平;创面造模后14 d,获取创面处皮肤组织,进行苏木精-伊红、Masson染色及细胞角蛋白14免疫组化染色。结果与结论:①3D打印多功能创面敷料具有良好的抗菌活性,对金黄色葡萄球菌、大肠杆菌与铜绿假单胞菌的抑菌圈直径分别为(4.15±0.09),(4.18±0.23),(4.35±0.13)cm。②随着造模时间的延长,小鼠创面逐渐愈合,治疗组、阳性药组造模后3,7,14 d的创面愈合率均高于放创模型组(P<0.01,P<0.001),并且治疗组创面愈合率高于阳性药组。随着造模时间的延长,小鼠血清白细胞介素水平呈先升高后降低的趋势,治疗组造模后3,7,14 d的血清白细胞介素水平均低于放创模型组。苏木精-伊红、Masson染色显示,单纯创伤组肉芽肿组织可见炎性细胞浸润,真皮层胶原纤维排列致密;放创模型组表皮层和真皮层正常结构被破坏,可见炎性细胞浸润;治疗组可见正常皮肤黏膜组织,表皮层排列规则紧密,汗腺、毛囊和真皮层胶原纤维排列整齐规则;阳性药组表皮层排列规则紧密,汗腺、毛囊和真皮层胶原纤维排列整齐规则。细胞角蛋白14免疫组化染色显示,治疗组表皮组织厚度低于其他3组(P<0.01,P<0.001)。③结果表明,3D打印多功能敷料具有局部麻醉、抗感染、促愈合多重功能。

关键词： 3D打印放创复合伤创面愈合多功能敷料敷料丝素蛋白

Effect of Sophora flavescens alkaloid on aerobic vaginitis in gel form for local treatment

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Journal of Traditional Chinese Medicine 2017年第3期37卷 314-320页

作者： Wang Xiu Li Jianchun Hu Yuzhen Chen Wenyang jin yiguang Department of Pharmaceutical Sciences Beijing Institute of Radiation Medi-cineBeijing 100850China Department of Pharmacy Beng-bu Medical CollegeBengbu 233030China Department of Pharmacy Bengbu Medical Col-legeBengbu 233030China Department of Pharmaceutical Sciences Bei-jing Institute of Radiation MedicineBeijing 100850China

OBJECTIVE: To investigate the effect of Sophora flavescens alkaloid(SFA) in gel form on aerobic vaginitis(AV) and the possible mechanism underlying the ***: AV rat models were prepared by intravaginal inoculation of Escherichia coli and Staphylococcus aureus. SFA gel and placebo gel were intravaginally administered. In vivo antibacterial effects,vaginal microenvironment, vaginal smears, pathological tissues of vaginas, and retention of gel in the vaginal cavity were ***: SFA gel had much higher antibacterial effect than placebo gel. SFA gel protected the vaginal mucosa from erosion of bacteria. At the same time,they inhibited the inflammatory responses, exhibiting little leukocytes and parabasal cells. Furthermore, the number of vaginal Lactobacilli remarkably increased following administration of SFA ***, the vaginal p H did not recover to thehealthy acidic levels after treatment due to the buffering effect of gel. The gel of a fluorescent agent,Cyanine 7, showed very long retention time in the vaginal cavity, up to more than 24 h, much longer than the ***: The SFA gel is a promising medicine for local treatment of AV with the advantages of anti-bacteria, protection of vaginal mucosa, increase of Lactobacilli, and long retention time in the vaginal cavity.

关键词： Matrine Escherichia coli Lactobacillus Administration, intravaginal Microenvironment Staphylococcus aureus

Interfacial properties and micellization of triblock poly(ethylene glycol)-poly(ε-caprolactone)-polyethyleneimine copolymers

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Acta Pharmaceutica Sinica B 2020年第6期10卷 1122-1133页

作者： Ji Li Yitian Du Haitao Su Shixuan Cheng Yanxia Zhou yiguang jin Xian-Rong Qi Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China

This study aimed to explore the link between block copolymers’interfacial properties and nanoscale carrier formation and found out the influence of length ratio on these characters to optimize drug delivery system.A library of diblock copolymers of PEG-PCL and triblock copolymers with additional PEI(PEG-PCL-PEI)were ***,a systematic isothermal investigation was performed to explore molecular arrangements of copolymers at air/water ***,structural properties and drug encapsulation in self-assembly were investigated with DLS,SLS and *** found the additional hydrogen bond in the PEG-PCL-PEI contributes to film stability upon the hydrophobic interaction compared with ***-PCL-PEI assemble into smaller micelle-like(such as PEGPCL4006-PEI)or particle-like structure(such as PEG-PCL8636-PEI)determined by their hydrophilic and hydrophobic block *** distinct structural architectures of copolymer are consistent between interface and *** the disparity of constituent ratio,we discovered the arrangement of both chains guarantees balanced hydrophilic-hydrophobic ratio in self-assembly to form stable ***,the structural differences were found to have significant influence on model drugs incorporation including docetaxel and *** together,these findings indicate the correlation between molecular arrangement and self-assembly and inspire us to tune block compositions to achieve desired nanostructure and drug loading.

关键词： Block copolymers Langmuir films Molecular arrangement Self-assembly Nanostructure

青蛙皮肤活性肽QUB2984的重组表达及体外活性评价

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中国组织工程研究 2024年第17期28卷 2675-2681页

作者：唐子琰顾顺强陈小玲王蕾马成帮周玫陈天豹杜丽娜金义光军事科学院军事医学研究院辐射医学研究所北京市100850 武警宁夏总队医院急诊科宁夏回族自治区银川市750000 英国贝尔法斯特女王大学药学院天然药物研究组英国贝尔法斯特BT71NN

背景:青蛙活性肽有丰富活性,如抗菌、抗肿瘤,有望解决抗生素耐药性问题。目的:从红眼树蛙皮肤分泌物中发现活性肽QUB2984,采用生物信息学手段模拟其结构和性质,合成、纯化、鉴定该肽并考察其生物学功能。方法:采用电刺激得到红眼树蛙皮... 详细信息

背景:青蛙活性肽有丰富活性,如抗菌、抗肿瘤,有望解决抗生素耐药性问题。目的:从红眼树蛙皮肤分泌物中发现活性肽QUB2984,采用生物信息学手段模拟其结构和性质,合成、纯化、鉴定该肽并考察其生物学功能。方法:采用电刺激得到红眼树蛙皮肤分泌物,分离出mRNA构建cDNA文库,测序得到肽序列。用生物大分子序列搜索工具进行肽序列比对,蛋白质结构模型和功能预测工具开展蛋白二级结构模拟。通过固相合成法合成多肽、反向高效液相进行纯化、基质辅助激光解吸电离飞行时间质谱进行验证。所获得的纯肽用于生物活性评价,采用最小抑菌浓度法评价其抗菌作用,MTT法检测其细胞毒作用,溶血实验考察其安全性。结果与结论:①所得活性肽QUB2984的结构预测为α-螺旋,有完整的疏水面,对生物膜有一定破坏能力,其序列上第3个氨基酸位置由W组成,并具有G-X-G结构;②活性肽QUB2984对革兰阳性金黄色葡萄球菌的最小抑菌浓度为2μmol/L,对革兰阴性大肠杆菌的最小抑菌浓度为2μmol/L,对真菌白色念珠菌的最小抑菌浓度为8μmol/L;③活性肽QUB2984在10^(-5)mol/L浓度下对人非小细胞肺癌细胞NCI-H838具有明显抑制作用,在64μmol/L浓度下对马红细胞的溶血作用为50%;④结果显示,QUB2984具有抗菌抑癌活性,其带+3正电荷,有利于与细菌或细胞接触。

关键词：生物活性肽生物合成结构模拟构效关系分离纯化抗菌抑癌溶血评价

Recent progress in drug delivery

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Acta Pharmaceutica Sinica B 2019年第6期9卷 1145-1162页

作者： Chong Li Jiancheng Wang yiguang Wang Huile Gao Gang Wei Yongzhuo Huang Haijun Yu Yong Gan Yongjun Wang Lin Mei Huabing Chen Haiyan Hu Zhiping Zhang yiguang jin College of Pharmaceutical Sciences Southwest UniversityChongqing 400715China Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China Key Laboratory of Smart Drug Delivery Ministry of EducationFudan UniversityShanghai 201203China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmaceutical Sciences(Shenzhen) Sun Yat-sen UniversityGuangzhou 510275China School of Radiation Medicine and Protection Soochow UniversitySuzhou 215123China School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China School of Pharmacy Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China

Drug delivery systems(DDS)are defined as methods by which drugs are delivered to desired tissues,organs,cells and subcellular organs for drug release and absorption through a variety of drug *** usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility,drug aggregation,low bioavailability,poor biodistribution,lack of selectivity,or to reduce the side effects of therapeutic *** 2015-2018,significant progress in the research on drug delivery systems has been achieved along with advances in related fields,such as pharmaceutical sciences,material sciences and biomedical *** review provides a conciseoverview of current progress in this research area through its focus on the delivery strategies,construction techniques and specific *** is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.

关键词： Pharmaceutics Drug delivery system Basic research Application Delivery strategy