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脂质体体外释放方法的研究进展

中国医药工业杂志 2024年第4期55卷 445-455页

作者：高冬旭赵源陆伟根何军胡清源中国医药工业研究总院医药先进制造国家工程研究中心上海201203

近年来,脂质体产品陆续上市。然而,各国药典中并未收录脂质体药物体外释放度检测的标准化方法,给脂质体药物的开发和监管带来了极大的挑战。体外释放度是评估药物制剂产品质量的重要技术指标,在产品开发、质量研究以及产品放行等方面具... 详细信息

近年来,脂质体产品陆续上市。然而,各国药典中并未收录脂质体药物体外释放度检测的标准化方法,给脂质体药物的开发和监管带来了极大的挑战。体外释放度是评估药物制剂产品质量的重要技术指标,在产品开发、质量研究以及产品放行等方面具有关键作用。文章介绍了国内外报道的脂质体产品体外释放方法及检测装置,并阐述了已上市产品体外释放方法的选择依据,期望促进和完善脂质体体外释放度检测方法的发展,为脂质体产品的研发和监管提供更科学、准确的数据支持。

关键词：脂质体体外释放评价方法质量评价

Reductive lipid nanoparticles loaded with vinorelbine inhibit chemotherapy-induced invasion of cancer cells by modulating ENPP2

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Nano Research 2024年第4期17卷 2886-2898页

作者： Xiaoqi Zhao Xuemeng Guo Mei Pang weigen Qiu Zhenyu luo Qing Lin Yichao lu Hang Yin Sijie Wang Huihui Liu Junlei Zhang Lihua luo Jian You College of Pharmaceutical Sciences Zhejiang University866 Yuhangtang RoadHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China

Cancer is a predominant culprit behind worldwide death and accounts for up to 10 million deaths every *** is the primary therapeutic method employed for cancer in clinical settings and is essential in controlling tumor *** the advances in this field,tumor invasion and metastasis during treatment remain a significant cause of treatment ***,the underlying mechanisms involving such a disappointing phenomenon are still not fully ***(VNB)extends the lifespan of many cancer patients in the clinic as an emerging chemotherapy drug approved by Food and Drug Administration(FDA).However,VNB-induced tumor metastasis is still an intractable problem,which may be closely related to the abnormal oxidative stress generated during VNB-mediated ***,the study aims to construct a reductive nanosystem loaded with VNB,called VNB-VNP,to improve cancer cure rates and reduce tumor *** the reductive component vitamin E,VNB-VNP can effectively reduce oxidative stress and significantly outperform free VNB in preventing tumor *** transcriptome analysis shows that VNB-VNP can alleviate the over-expression of ectonucleotide pyrophosphatase/phosphodiesterase 2(ENPP2),which may be the main reason why VNB-VNP can inhibit tumor invasion and ***,the research designs a new platform for VNB treatment,which demonstrates promising efficacy in inhibiting neoplastic progression and identifies a new mechanism associated with VNB-induced tumor metastasis,which may offer several valuable references for enhancing chemotherapy efficacy in clinical anti-tumor therapy.

关键词： chemotherapy vinorelbine tumor Invasion lysophosphatidic acid ectonucleotide pyrophosphatase/phosphodiesterase 2(ENPP2)

A novel tumor-targeting treatment strategy uses energy restriction via co-delivery of albendazole and nanosilver

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Nano Research 2018年第9期11卷 4507-4523页

作者： Jianming Liang Ruixiang Li Yuwei He Chengli Ling Qi Wang Yongzhuo Huang Jing Qin weigen lu Jianxin Wang Department of Pharmaceutics School of Pharmacy Fudan University & Key Laboratory of Smart Drug Delivery Ministry of Education Shanghai 201203 China Institute of Clinical Pharmacology Guangzhou University of Traditional Chinese Medicine Guangzhou 510006 China Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Rd. Shanghai201203 China Shanghailnstitute of Pharmaceuticallndustry China State Institute of Pharmaceutical Industry 285 Gebaini Rd. Shanghai201203 China School of Pharmacy Chengdu University of Traditional Chinese Medicine No 1166 Liu TaiAvenue Wenjiang District Chengdu 610072 China

Although nanotechnology has been rapidly developed and applied in tumor targeting, the outcome of chemotherapy remains greatly restricted by the toxicity of cytotoxic drugs in normal tissues and cells. Therefore, the development of alternative delivery systems, with few side effects in normal cells, has attracted increasing attention. Energy restriction is a novel and promising approach to cancer treatment, which can restrict tumor growth via inhibition of cellular energy metabolism. In this study, a novel tumor targeting system, based on folate-conjugated bovine serum albumin （BSA）, was developed to co-deliver albendazole and nanosilver simultaneously, to restrain the energy metabolism of tumor cells. This nanosystem showed stronger anti-tumor efficacy than those using nanoparticles without folic acid modification, nanosilver, or albendazole, both in vitro and in vivo. This nanosystem depleted cellular ATP via direct inhibition of glycolytic enzymes and mitochondrial damage, resulting in inhibition of proliferation, cell-cycle arrest, and apoptosis of tumor cells. The enhanced anti-tumor activity contributed to the tumor-targeting ability of this system, resulting in specific energy inhibition in tumor cells. Toxicity evaluation was performed to confirm the safety of this system. This nanosystem provides an efficient and safe strate~ for tumor therapy.

关键词： albendazole nano silver co-delivery tumor targeting energy metabolism

Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy

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Acta Pharmaceutica Sinica B 2019年第4期9卷 843-857页

作者： Caifang Gao Jianming Liang Ying Zhu Chengli Ling Zhekang Cheng Ruixiang Li Jing Qin weigen lu Jianxin Wang Department of Pharmaceutics School of PharmacyFudan University&Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai 201203China Shanghai Institute of Pharmaceutical Industry China State Institute of Pharmaceutical IndustryShanghai 201203China Guangzhou University of Chinese Medicine Guangzhou 510006China School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China School of Pharmacy Minzu University of ChinaBeijing 100081China

Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood–brain barrier(BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the ***, it is urgent and necessary to discover more safe and effective BBB penetration and gliomatargeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer *** nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of mentholmodified casein nanoparticles(M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-MCA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining ofthe organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.

关键词： Glioma Casein Menthol Nanoparticles Brain targeting Blood–brain barrier 10-Hydroxycamptothecin

Selective ischemic-hemisphere targeting Ginkgolide B liposomes with improved solubility and therapeutic efficacy for cerebral ischemia-reperfusion injury

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Asian Journal of Pharmaceutical Sciences 2023年第2期18卷 76-93页

作者： Yang Li Miaomiao Zhang Shiyi Li Longlong Zhang Jisu Kim Qiujun Qiu weigen lu Jianxin Wang Department of Pharmaceutics School of PharmacyFudan University&Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China National Pharmaceutical Engineering and Research Center China State Institute of Pharmaceutical IndustryShanghai 201203China

Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic *** of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of *** B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke ***,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a ***,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes *** amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)*** to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h *** levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and *** addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy ***,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeu

关键词： Ginkgolide B Cerebral ischemia reperfusion injury(CI/RI) Docosahexaenoic acid Liposomes Brain targeting Microglia

Light touch in quantum:an interview with *** Haroche

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Advanced Photonics 2024年第1期6卷 10-16页

作者： Chao-Yang lu CAS Centre for Excellence in Quantum Information and Quantum Physics HefeiChina NYU Shanghai NYU-ECNU Institute of PhysicsShanghaiChina University of Science and Technology of China Department of Modern PhysicsShanghaiChina

lu:Hello,***,nice to see you again!Let us start the *** 2012,you and David Wineland won the Nobel Prize in *** you describe your work in simple terms to a general audience?And can you tell us how you were originally interested in this field and got into this study?Haroche:Maybe I should start with the second part of the question.I got interested in atomic physics when I was a student atÉcole Normale Supérieure(ENS)in Paris in the 1960s.

关键词： quantum interview Serge

Optical grade (Gd_(0.95-x)lu_(x)Eu_(0.05))_(3)Al_(5)O_(12) ceramics with near-zero optical loss: Effects of lu^(3+) doping on structural feature, microstructure evolution, and far-red luminescence

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Journal of Advanced Ceramics 2024年第1期13卷 113-123页

作者： Zhigang Sun Ji-Guang Li Huiyu Qian Yoshio Sakka Tohru SSuzuki Bin lu School of Materials Science and Chemical Engineering Ningbo UniversityNingbo 315211China Research Center for Electronic and Optical Materials National Institute for Materials ScienceIbaraki 305-0044Japan Key Laboratory of Photoelectric Detection Materials and Devices of Zhejiang Province Ningbo 315211China

A chemical co-precipitation strategy was employed to synthesize a series of(Gd_(0.95−x)lu_(x)Eu_(0.05))_(3)Al_(5)O_(12)(x=0.1−0.95)powder phosphors,followed by vacuum sintering to achieve transparent garnet ceramic *** density functional theory indicated lu_(3)Al_(5)O_(12) was formed in priority compared with Gd_(3)Al_(5)O_(12) during solid-phase *** high-temperature sintering,the lu^(3+)substitution for Gd^(3+)suppressed point mass diffusion leading to a smaller grain *** in-line transmittances of bulk specimens with x=0.1,0.3,0.5,0.7,and 0.95 nm were~83.5%,80.1%,68.8%,73.7%,and 82.2%at 710 nm(Eu^(3+)emission center),respectively,among which the sample of x=0.1 exhibited the optical grade with near-zero optical loss in agreement with the defect-free single crystal(~100%of the theoretical transmittance).The resulting particle and ceramic materials both presented characteristic Eu^(3+)emission arising from 5D0→7FJ(J=1−4)transition,where the dominant far-red emission at~710 nm arising from ^(5)D_(0)→^(7)F_(4) transition overlapped with the absorption of phytochrome(PFR).The photoluminescence excitation and photoluminescence intensities of(Gd_(0.95−x)lu_(x)Eu_(0.05))_(3)Al_(5)O_(12) powders and ceramics generally increased at a higher Gd^(3+)/lu^(3+)***^(3+)dopants delayed the fluorescence lifetime while the bulk samples had shorter lifetime compared to the particle *** transparent(Gd_(0.85)lu_(0.1)Eu_(0.05))3Al_(5)O_(12) ceramic phosphor exhibited good thermal stability with a high thermal quenching temperature above 533 *** designed ceramic phosphor-converted light-emitting diode had a saturation injection current of 435 mA and a current-dependent color rendering *** importantly,our report marked the developmental stage of transparent ceramic materials towards zero optical loss.

关键词： transparent ceramics garnet phosphors light-emitting diode(LED) optical properties Gibbs free energy

Collective Molecular Machines: Multidimensionality and Reconfigurability

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Nano-Micro Letters 2024年第8期16卷 309-340页

作者： Bin Wang Yuan lu Department of Chemical Engineering Tsinghua UniversityBeijing 100084People’s Republic of China Key Laboratory of Industrial Biocatalysis Ministry of EducationTsinghua UniversityBeijing 100084People’s Republic of China

Molecular machines are key to cellular activity where they are involved in converting chemical and light energy into efficient mechanical *** the last 60 years,designing molecular structures capable of generating unidirectional mechanical motion at the nanoscale has been the topic of intense *** progress has been made,attributed to advances in various fields such as supramolecular chemistry,biology and nanotechnology,and ***,individual molecular machines are only capable of producing nanometer work and generally have only a single *** order to address these problems,collective behaviors realized by integrating several or more of these individual mechanical units in space and time have become a new *** this review,we comprehensively discuss recent developments in the collective behaviors of molecular *** particular,collective behavior is divided into two *** is the appropriate integration of molecular machines to efficiently amplify molecular motions and deformations to construct novel functional *** other is the construction of swarming modes at the supramolecular level to perform nanoscale or microscale *** discuss design strategies for both modes and focus on the modulation of features and ***,in order to address existing challenges,the idea of transferring experience gained in the field of micro/nano robotics is presented,offering prospects for future developments in the collective behavior of molecular machines.

关键词： Molecular machines Collective control Collective behaviors DNA Biomolecular motors

Soil inorganic amendments produce safe rice by reducing the transfer of Cd and increasing key amino acids in brown rice

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Journal of Environmental Sciences 2024年第2期136卷 121-132页

作者： Fanyi Kong Shenggao lu Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment Key Laboratory of Environmental Remediation and Ecosystem HealthMinistry of EducationCollege of Environmental and Resource SciencesZhejiang UniversityHangzhou 310058China

The digestibility of cadmium(Cd)in brown rice is directly related to amino acid metabolism in rice and human *** our field study,three kinds of alkaline calcium-rich soil inorganic amendments(SIAs)at three dosages were applied to produce safe rice and improve the quality of rice in Cd-contaminated *** the increased application of SIA,Cd content in iron plaque on rice root significantly increased,the transfer of Cd from rice root to grain significantly decreased,and then Cd content in brown rice decreased *** vitro digestibility of Cd in brown rice was estimated by a physiologically based extraction *** showed that more than 70%of Cd in brown rice could be digested by simulated gastrointestinal *** on the total and digestible Cd contents in brown rice to evaluate the health risk,the application of 2.25 ton SIA/ha could produce safe rice in acidic slightly Cd-contaminated paddy *** amino acids(AAs)in brown rice were determined by high-performance liquid *** contents of 5 key AAs(KAAs)that actively respond to environmental changes increased significantly with the increased application of *** structural equation model indicated that KAAs could be affected by the Cd translocation capacity from rice root to grain,and consequently altered the ratio of indigestible Cd in brown *** formation of indigestible KAAs-Cd complexes by combining KAAs(phenylalanine,leucine,histidine,glutamine,and asparagine)with Cd in brown rice could be considered a potential mechanism for reducing the digestibility of Cd.

关键词： Cadmium digestibility Soil inorganic amendments Safe rice Amino acid Priming effect Health risk