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Synthesis of Organic-Inorganic Hybrid Aluminum Hypophosphite Microspheres Flame Retardant and Its Flame Retardant Research on Thermoplastic Polyurethane

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Journal of Wuhan University of Technology(Materials Science) 2024年第1期39卷 221-233页

作者：刘生鹏 XU Zhi ZHANG Xinyuan WEI Huan XIONG Yun DING Yigang HUANG Wenbo 许莉莉 Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education Key Laboratory for Green Chemical Process of Ministry of EducationSchool of Chemical Engineering and PharmacyWuhan Institute of TechnologyWuhan 430205China Hubei Three Gorges Laboratory Yichang 443007China school of Technology Materials Science and Engineering Wuhan Institute of TechnologyWuhan 430205China

Aluminum hypophosphite microspheres(AHP) were synthesized by hydrothermal method using NaH2PO2·H2O and AlCl3·6H2O as raw materials, and then the AHP microspheres were polymerized by surface polymerization of micro-nanospheres with cyclic cross-linked poly(cyclotriphosphazene-co-4,4'-sulfonyldiphenol)(PZS). A new organic-inorganic poly(phosphonitrile)-modified aluminum hypophosphite microspheres(PZS-AHP) were synthesized by encapsulation and applied to flame retardant thermoplastic polyurethane(TPU). The microstructure and chemical composition of the PZS-AHP microsphere were characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and X-ray spectroscopy. The thermal stability of PZS-AHP microsphere was explored with thermogravimetric analysis. Thermogravimetric data indicate that the PZS-AHP microspheres have excellent thermal stability. The thermal and flame-retarding properties of the TPU composites were evaluated by thermogravimetric(TG), limited oxygen index tests(LOI), and cone calorimeter test(CCT). The TPU composite achieved vertical burning(UL-94) V-0 grade and LOI value reached 29.2% when 10 wt% PZS-AHP was incorporated. Compared with those of pure TPU, the peak heat release rate(pHRR) and total heat release(THR) of TPU/10%PZS-AHP decreased by 82.2% and 42.5%, respectively. The results of CCT indicated that PZS-AHP microsphere could improve the flame retardancy of TPU composites.

关键词： polyphosphazene thermoplastic polyurethane flame retardancy aluminum hypophosphite surface polymerization

Protective effect of glycyrrhetinic acid against cantharidin-induced hepatotoxicity through reducing oxidative stress in mice

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Toxicology Advances 2024年第1期6卷 3-9页

作者： Li-Juan Xiong Xiao-Hong Zhang Jia-Lu Zou Xuan Chen Wen-Zhong Feng Cong-Yun Meng Jian-Yong Zhang school of pharmacy Zunyi medical universityZunYi 563000China

Background:Cantharidin(CTD)is a commonly used natural product with anticancer properties;however,it has significant adverse effects,particularly *** acid(GA),the active component of licorice,shows potential hepatoprotective *** protective effects and mechanism of GA against CTD-induced hepatotoxicity are still ***:This study aims to elucidate the effect and mechanism of GA on CTD-induced hepatotoxicity in mice ***:Construction of CTD-induced hepatotoxicity models and oral gavage GA intervention for 14 *** liver index,ALT,AST and LDH levels in the serum of the mice were examined;HE staining was performed to observe pathological changes in the *** MDA level and SOD activities in liver tissue were *** blot was conducted to determine Keap1/Nrf2 signaling pathway-related protein ***:The results showed that GA significantly reduced the levels of ALT,AST,and LDH in the serum,which were increased by ***,it also exerted a substantial inhibitory effect on the reduction of SOD activity and the elevation of malondialdehyde content in liver ***,the phenomena of nuclear swelling,necrosis,and inflammatory infiltration of liver tissue were significantly attenuated following oral administration of GA in *** research has demonstrated that GA effectively suppressed the CTD-triggered upregulation of Keap1 while increasing the CTD-induced downregulation of Nrf2,HO-1,and ***:These findings suggested that GA may protect against CTD-induced hepatotoxicity in mice by exerting antioxidative stress through the Keap1/Nrf2 signaling pathway.

关键词： glycyrrhetinic acid cantharidin hepatotoxicity oxidative stress Nrf2/Keap1

Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies

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Asian Journal of Pharmaceutical Sciences 2024年第3期19卷 177-189页

作者： Zhining Ma Yuequan Wang Huiyang He Tong Liu Qikun Jiang Xiaohong Hou school of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Liaoning Provincial Institute of Drug Inspection and Testing Shenyang 110036China school of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China

Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory ***,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory ***,the limited corneal permeability of FB significantly restricts its *** this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-***,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer *** the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1

关键词： Flurbiprofen Anti-inflammatory Ophthalmic delivery Chiral resolution Ion-pairing

In situ tumor vaccine with optimized nanoadjuvants and lymph node targeting capacity to treat ovarian cancer and metastases

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4102-4117页

作者： Yuan Li Fan Tong Yufan Wang Jing Wang Manqi Wu Hanmei Li Hongyan Guo Huile Gao Department of Obstetrics and Gynecology National Clinical Research Center for Obstetrics and GynecologyPeking University Third HospitalBeijing 100191China Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China school of Food and Biological Engineering Chengdu UniversityChengdu 610106China

Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate ***,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and ***,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian *** CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@*** from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T ***,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in ***,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.

关键词： In situ nano-vaccine Lymph node targeting MMP-2 responsive PD-1 Combination therapy CpG Ovarian cancer Metastases

Legumain-triggered aggregable gold nanoparticles for enhanced intratumoral retention

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Chinese Chemical Letters 2024年第7期35卷 388-393页

作者： Zhi Li Wenpei Li Shaoping Jiang Chuan Hu Yuanyu Huang Maxim Shevtsov Huile Gao Shaobo Ruan Advanced Research Institute of Multidisciplinary Sciences School of Life ScienceBeijing Institute of TechnologyBeijing 100081China Key Laboratory of Drug Targeting and Drug Delivery System West China School of PharmacySichuan UniversityChengdu 610041China Institute of Cytology of Russian Academy of Sciences(RAS) St.Petersburg 194064Russia

Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical ***,we proposed a legumain-triggered aggregable gold nanoparticle(GNP)delivery platform(GNPs-A&C).GNPs-A&C could form intratumoral or intracellular aggregates in response to the overexpressed *** aggregates with size increase not only could reduce back-flow from interstitial space to peripheral bloodstream but also could restrict the cellular exocytosis,leading to enhanced intratumoral *** vitro studies demonstrated that GNPs-A&C possessed an excellent legumain responsiveness and the increased size was closely relevant with legumain *** vivo studies demonstrated GNPs-A&C possessed slower clearance rate and much higher intratumoral retention within legumain-overexpressed tumor compared to non-aggregable NPs,regardless of intravenous or intratumoral *** importantly,this delivery platform significantly improved the chemotherapeutic effect of doxorubicin(DOX)towards subcutaneous xenograft C6 *** effectiveness of this stimulus-responsive aggregable delivery system provides a thinking for designing more intelligent size-tunable nanomedicine that can substantially improve intratumoral retention.

关键词： Legumain Size-tunable Enhanced retention Stimulus-responsive Nanomedicine

Therapeutic potential and pharmacological mechanism of visnagin

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Journal of Integrative Medicine 2024年第4期22卷 399-412页

作者： Poonam Yadav Sumeet Kumar Singh Sayantap Datta Saloni Verma Aarti Verma Arnab Rakshit Anjana Bali Jasvinder Singh Bhatti Amit Khurana Umashanker Navik Department of Pharmacology School of Health SciencesCentral University of PunjabBathindaPunjab 151401India Department of Pharmacological and Pharmaceutical Sciences College of PharmacyUniversity of HoustonHoustonTX 77204-5000USA Department of Human Genetics and Molecular Medicine School of Health SciencesCentral University of PunjabBathindaPunjab 151401India

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga(L.)Lam(a synonym of Visnaga daucoides Gaertn.)plant,which is used to cure various *** investigations into the bioactive properties of visnagin have been studied to *** literature on visnagin demonstrates its biological properties,including anti-inflammatory,anti-diabetic,and beneficial effects in cardiovascular and renal ***,visnagin improves sperm quality parameters,stimulates steroidogenesis,and increases serum gonadotropins and testosterone levels,while decreasing proinflammatory cytokines,oxidative damage,genomic instability,and it modulates ***,visnagin has emerged as an exciting lead for further research,owing to its potential in various unmet clinical *** current review summarized its basic structure,pharmacokinetics,and pharmacological effects,focusing on its mechanisms of *** review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin’s safe clinical use.

关键词： Visnagin Phytochemical Anti-inflammatory Ammi visnaga L. Visnaga daucoides Gaertn Cancer

A novel dual serotonin transporter and M-channel inhibitor D01 for antidepression and cognitive improvement

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1457-1466页

作者： Yaqin Wei Xiangqing Xu Qiang Guo Song Zhao Yinli Qiu Dongli Wang Wenwen Yu Yani Liu KeWei Wang school of pharmacy Xuzhou Medical UniversityXuzhou 221004China Institute of Pharmaceutical Research Jiangsu Nhwa Pharmaceutical Co.Ltd.&Jiangsu Key Laboratory of Central Nervous System Drug Research and DevelopmentXuzhou 221116China Department of Pharmacology School of PharmacyQingdao University Medical CollegeQingdao 266073China Institute of Innovative Drug Qingdao UniversityQingdao 266021China Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhou 510515China

Cognitive dysfunction is a core symptom common in psychiatric disorders including depression that is primarily managed by antidepressants lacking efficacy in improving *** this study,we report a novel dual serotonin transporter and voltage-gated potassium Kv7/KCNQ/M-channel inhibitor D01(a 2-methyl-3-aryloxy-3-heteroarylpropylamines derivative)that exhibits both anti-depression effects and improvements in cognition.D01 inhibits serotonin transporters(K_(i)=30.1±6.9 nmol/L)and M channels(IC_(50)=10.1±2.4μmol/L).D01 also reduces the immobility duration in the mouse FST and TST assays in a dose-dependent manner without a stimulatory effect on *** administrations of D01(20 and 40 mg/kg)can significantly shorten the immobility time in a mouse model of chronic restraint stress(CRS)-induced depression-like ***,D01 dose-dependently improves the cognitive deficit induced by CRS in Morris water maze test and increases the exploration time with novel objects in normal or scopolamine-induced cognitive deficits in mice,but not ***,D01 reverses the long-term potentiation(LTP)inhibition induced by *** together,our findings demonstrate that D01,a dual-target serotonin reuptake and M channel inhibitor,is highly effective in the treatment-resistant depression and cognitive deficits,thus holding potential for development as therapy of depression with cognitive deficits.

关键词： SERT 5-HT Kv7/KCNQ/M current D01 Depression Cognition

Bacterial and cancerous cell membrane fused liposome coordinates with PD-L1 inhibitor for cancer immunotherapy

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Nano Research 2024年第9期17卷 8389-8401页

作者： Xianjin Luo Chenglong Li Zhaofei Guo Hairui Wang Penghui He Yuanhao Zhao Yi Lin Chunting He Yingying Hou Yongshun Zhang Guangsheng Du Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610064China Pharmaceutical Biotechnology Department of PharmacyLMU MunichButenandt Strasse 5-13Munich 81377Germany Department of Biomedical Engineering College of Future TechnologyPeking UniversityBeijing 100871China

Although tumor cell membranes with broad-spectrum antigens have been explored for cancer vaccines for decades,their relatively poor capacity to stimulate immune responses,especially cellular immune responses,has limited their ***,we presented a novel bacterial and cancerous cell membrane fusogenic liposome for co-delivering cell membrane-derived antigens and ***,a programmed death-ligand 1(PD-L1)inhibitor,JQ-1,was incorporated into the formulation to tackle the up-regulated PD-L1 expression of antigen-presenting cells(APCs)upon vaccination,thereby augmenting its anti-tumor *** fusogenic liposomes demonstrated significantly improved cellular uptake by APCs and effectively suppressed PD-L1 expression in bone marrow-derived dendritic cells(BMDCs)in *** subcutaneous vaccination,the nano-vaccines efficiently drained to the tumor-draining lymph nodes(TDLNs),and significantly inhibited PD-L1 expression of both dendritic cells(DCs)and macrophages within the TDLNs and *** a result,the liposomal vaccine induced robust innate and cellular immune responses and inhibited tumor growth in a colorectal carcinoma-burden mouse *** summary,the fabricated cell membrane-based fusogenic liposomes offer a safe,effective,and easily applicable strategy for tumor immunotherapy and hold potential for personalized cancer immunotherapy.

关键词： fusogenic liposome tumor cell membrane adjuvant programmed death-ligand 1(PD-L1)inhibitor tumor draining lymph nodes

Endoplasmic reticulum-targeted delivery of celastrol and PD-L1 siRNA for reinforcing immunogenic cell death and potentiating cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3643-3660页

作者： Jie Wang Zilong Zhang Yan Zhuo Zhuan Zhang Rongrong Chen Li Liang Xiaohe Jiang Di Nie Chang Liu Zhiwen Zou Xiang Li Jiaxin Li Bingqi Wang Rui Wang Yong Gan Miaorong Yu school of pharmacy Shanghai University of Traditional Chinese MedicineShanghai 201203China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Jiangxi Medical College Nanchang UniversityNanchang 330006China school of pharmacy Nanjing University of Chinese MedicineNanjing 210023China University of Chinese Academy of Sciences Beijing 100049China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum(ER)presents an opportunity to amplify the synergistic effects of chemotherapy and *** this study,we initially validated celastrol(CEL)as an inducer of immunogenic cell death(ICD)by promoting ER stress and autophagy in colorectal cancer(CRC)***,an ER-targeted strategy was posited,involving the codelivery of CEL with PD-L1 small interfering RNAs(siRNA)using KDEL peptide-modified exosomes derived from milk(KME),to enhance chemoimmunotherapy *** findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER *** to their non-targeting counterparts,KME exhibited a significant augmentation of the CEL-induced ICD ***,it facilitated the release of danger signaling molecules(DAMPs),thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the ***,the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression,consequently fostering the proliferation and activity of CD8^(+)T ***,the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in ***,a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

关键词： Chemoimmunotherapy Targeted drug delivery Endoplasmic reticulum Endoplasmic reticulum stress Immunogenic cell death siRNA Chemoimmunotherapy Targeted drug delivery Endoplasmic reticulum Endoplasmic reticulum stress Immunogenic cell death siRNA