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Chiral mesoporous silica nano-screws as an efficient biomimetic oral drug delivery platform through multiple topological mechanisms

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1432-1446页

作者： Yumei Wang Jia Ke Xianmou Guo Kaijun Gou Zhentao Sang Yanbu Wang Yan Bian Sanming Li Heran Li department of pharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China school of Pharmacy China Medical UniversityShenyang 110122China

In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws(CMSWs) with ideal topological structures(e.g., small section area, relative rough surface,screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bioadhesion, mucus-penetration and cellular uptake(contributed by the macropinocytosis and caveolaemediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres(CMSSs)and chiral mesoporous silica nanorods(CMSRs), achieving extended retention duration in the gastrointestinal(GI) tract and superior adsorption in the blood circulation(up to 2.61-and 5.65-times in AUC).After doxorubicin(DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier(IEB), and resulted in satisfactory oral bioavailability of DOX(up to 348%).CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.

关键词： Chiral mesoporous silica Nano-screw Morphology Geometric topological structure Intestinal epithelium barrier Oral adsorption

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A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms, and future perspectives

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2396-2415页

作者： Yujie Shi An Lu Xiangyu Wang Zakia Belhadj Jiancheng Wang Qiang Zhang Beijing Key Laboratory of Molecular pharmaceutics and New Drug Delivery Systems School of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations(LAPFs)with the aim of improving drug pharmacokinetics and therapeutic *** have been proven to extend the half-life of therapeutics,as well as to improve patient adherence;consequently,this enhances the outcome of therapy *** past decades,considerable progress has been made in designing effective LAPFs in both preclinical and clinical *** we review the latest advances of LAPFs in preclinical and clinical stages,focusing on the strategies and underlying mechanisms for achieving long *** strategies are classified into manipulation of in vivo clearance and manipulation of drug release from delivery systems,*** the current challenges and prospects of each strategy are *** addition,we also briefly discuss the design principles of LAPFs and provide future perspectives of the rational design of more effective LAPFs for their further clinical translation.

关键词： Long-acting Chemical modification Fc/HSA fusion Biomimetic strategies Hydrogels Nanocrystal suspensions Microneedles Implantable systems

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Comparative Study on Characteristics and Cytotoxicity of Bifunctional Magnetic-Silver Nanostructures: Synthesized Using Three Different Reducing Agents

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Acta Metallurgica Sinica(English Letters) 2016年第4期29卷 326-334页

作者： Narjes Ebrahimi Sara Rasoul-Amini Alireza Ebrahiminezhad Younes Ghasemi Ahmad Gholami Hassan Seradj department of pharmaceutical Biotechnology School of Pharmacy Shiraz University of Medical Sciences department of Medicinal Chemistry School of PharmacyShiraz University of Medical Sciences Shiraz Fars Iran pharmaceutical sciences Research Center Shiraz University of Medical Sciences department of Medical Biotechnology School of MedicineFasa University of Medical Sciences department of Pharmacognosy School of Pharmacy Shiraz University of Medical Sciences

Magnetic-silver nanostructures were synthesized via optimized chemical conditions, and their characteristics and cytotoxicity were compared as candidates for the magnetic delivery of silver nanoparticles toward cancer cells. Magnetic-silver nanostructures were prepared through the reduction of silver ions in the presence of iron oxide nanoparticles using three different reducing agents （glucose, maltose and sodium citrate）. Their physicochemical characteristics were determined using ultraviolet-visible spectroscopy, X-ray diffraction analysis, transmission electron microscopy, selected area electron diffraction analysis, Fourier transformed infrared spectroscopy, atomic absorption spectroscopy, vibrating sample magnetometry and differential scanning calorimetry. Cytotoxic activities were evaluated against a human liver hepatocellular carcinoma cell line. Fabricated nanostructures, which exhibit differences in size, silver content, magnetic saturation value and cytotoxicity, represent sufficient superparamagnetic properties and considerable cytotoxicity to be suggested as effective tools in magnetic targeting of silver nanoparticles as an approach to cancer therapy.

关键词： Bifunctional nanostructure Magnetic-silver nanostructure Silver nanoparticle Cytotoxicity Reducing agent

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Inhalable nanoparticles with enhanced cuproptosis and cGAS-STING activation for synergistic lung metastasis immunotherapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3697-3710页

作者： Chongzheng Yan Huaiyou Lv Yafei Feng Yuhan Li Zhongxi Zhao department of pharmaceutics Key Laboratory of Chemical Biology of Ministry of EducationSchool of Pharmaceutical SciencesCheelloo College of MedicineShandong UniversityJinan 250012China Key University Laboratory of pharmaceutics&Drug Delivery Systems of Shandong Province School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China department of Pharmacy Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityYantai 264001China

Due to the insufficient Cu^(+)accumulation,Cu^(+)efflux mechanism,and highly immunosuppressive tumor microenvironment(TME)in lung metastasis,the cuproptosis efficacy is ***,an inhalable nanodevice(CLDCu)is constructed to successfully overcome the drawbacks of *** consists of a Cu^(2+)-chitosan shell and low molecular weight heparin-tocopherol succinate(LMWH-TOS,LT)core with disulfiram(DSF)*** prepared CLDCu can be inhaled and accumulate in large amounts in lung lesions(63.6%)with 56.5 times higher than intravenous *** tumor cells,the mild acidity triggers the co-release of DSF and Cu2+,thus generating bis(diethyldithiocarbamate)-copper(CuET)to block Cu^(+)efflux protein ATP7B and forming toxic Cu^(+),leading to enhanced ***,the released chitosan cooperates with CLDCu-induced cuproptosis to activate stimulator of interferon genes(STING)pathway,which significantly potentiates dendritic cells(DCs)maturation,as wells as evokes innate and adaptive *** lung metastatic mice model,CLDCu is found to induce cuproptosis and reverse the immunosuppressive TME by inhalation ***,CLDCu combined with anti-programmed cell death protein ligand-1 antibody(aPD-L1)provokes stronger antitumor ***,nanomedicine that combines cuproptosis with STING activation is a novel strategy for tumor immunotherapy.

关键词： Cuproptosis cGAS-STING activation Disulfiram Inhalation administration Tumor microenvironment PD-L1 checkpoint blockade Lung metastasis Immunotherapy

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Glucocorticoids-based prodrug design:Current strategies and research progress

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Asian Journal of pharmaceutical sciences 2024年第3期19卷 41-78页

作者： Hongbing Liu Muse Ji Peifu Xiao Jingxin Gou Tian Yin Haibing He Xing Tang Yu Zhang department of pharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China school of Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China

Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and ***,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and *** notorious side effects seriously compromise patients'quality of life,especially in patients with chronic ***,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive *** them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising *** this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so ***,we also raise issues that need to be focused on during the development of glucocorticoid-based *** review is expected to be helpful for the research and development of novel GCs and prodrugs.

关键词： Glucocorticoids Prodrug design Targeted drug delivery Research progress

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Shape effect of prodrug nanoassemblies on treatment efficacy of cancer therapy

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Nano Research 2025年第2期18卷 616-626页

作者： Fengxiang Liu Rongzheng Liu Xiaoyuan Fan Xia Wang Kaiyuan Wang Hainan Zhao Hao Ye Shunzhe Zheng Xiao Kuang Yinxian Yang Haotian Zhang Qiming Kan Zhonggui He Jian Chen Jin Sun department of pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China school of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Nephrology department The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121000China Multi-Scale Robotics Lab(MSRL) Institute of Robotics&Intelligent Systems(IRIS)ETH Zurich 8092Switzerland school of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China school of Pharmacy Shanghai Jiao Tong UniversityShanghai 200240China

The tumor microenvironment-sensitive prodrug-based nanoparticles(NPs)have emerged as a promising drug delivery system(DDS).The shape of these particles plays a crucial role in their in vivo ***,non-spherical organic NPs are rarely reported due to the inherent flexibility and variability of organic ***,we fabricate reduction-sensitive prodrug NPs and explore the impact of their morphology properties on their in vivo *** are self-assembled into spherical NPs with distearoyl phosphoethanolamine-PEG2000(DSPE-PEG2k),or into rod-shaped NPs with D-a-tocopherol polyethylene glycol 2000 succinate(TPGS2k)due to the stronger binding *** comparison with spherical NPs,the endocytosis of rod-shaped NPs predominantly relies on caveolae-mediated pathways rather than clathrin-mediated ones,potentially avoiding degradation by ***,the rod-shaped NPs exhibit prolonged circulation time,increased tumor accumulation,and enhanced antitumor *** current findings reveal the significant effect of particle shape on the behavior of prodrug NPs and introduce a novel paradigm for high-efficacy cancer therapy of prodrug NPs.

关键词： camptothecin self-assembly prodrug-based nanoparticles nanorod cancer therapy

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Immunomodulation and Nigerian mistletoe immunomodulatory activities of n-hexane and methanol extracts of Loranthus micranthus Linn,parasitic on Parkia biglobosa.

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Asian Pacific Journal of Tropical Medicine 2008年第3期1卷 48-54页

作者： E.O.Omeje P.O.Osadebe F.B.C.Okoyea A.K.Agwu C.O.Esimone department of pharmaceutical and Medicinal Chemistry Faculty of Pharmaceutical SciencesUniversity of Nigeria Nsukka410001NsukkaNigeria department of pharmaceutics Faculty of Pharmaceutical SciencesUniversity of Nigeria Nsukka410001NsukkaNigeria

Loranthus micranthus is the species of mistletoe peculiar to the eastern province of *** has been shown to possess anti-diabetic,anumotility,antimicrobial and antihypertensive activities which are host-tree dependent. The antimicrobial activity was found to vary with the season during which the plant was *** are of the opinion that this species should possess immunomodulating potentials as have been reported for the European species,Viscum *** our efforts to establish the bio-activities and active principles in our local mistletoe, the immunomodulatory activity of n-hexane and methanol extracts from Loranthus micranthus parasitic on Persea americana was assessed at three dose levels ranging from 100 to 400 mg/kg body weight using delayed type hypersensitivity reaction(DTHR) and cyclophosphamide-induced myelosuppression models in *** was compared with responses from a standard immunostimulatory drug,*** phytochemical analysis of the plant showed the presence of tannins,flavonoids,alkaloids,terpenoids,carbohydrates and *** analysis indicated a dose-dependent response relationship in the parameters measured with over 170%increase for both extracts at the highest dose *** one way ANOVA test showed significant variation in the parameters between the controls and the different dose ***,at 95%confidence level,(P<0.05),there was no statistically significant difference between the two extracts, an indication that the active immunomodulant(s) could be both in the polar and non-polar crude *** conclusion,the present results have established some immune stimulating actions of the Eastern Nigeria mistletoe, Loranthus micranthus thus indicating that this variant of the semi parasitic plant holds a strong promise as an immunostimulatory *** is therefore,a basis for further detailed investigation on the fractions and specific ***,these extracts from Loranthus micranthu

关键词： immunomodulatory L.micranthus methanol mistletoe n-hexane V.album

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Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy

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Asian Journal of pharmaceutical sciences 2021年第6期16卷 784-793页

作者： Yinxian Yang Shiyi Zuo Linxiao Li Xiao Kuang Jinbo Li Bingjun Sun Shujun Wang Zhonggui He Jin Sun department of pharmaceutics College of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China department of pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China

Ferroptosis is a new mode of cell death,which can be induced by Fenton reactionmediated lipid ***,the insufficient H2O2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ***,a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin(DOX),iron and unsaturated lipid for efficient *** leveraging the coordination effect between DOX and Fe3+,trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient ***,Fe3+could react with the overexpressed GSH in tumor cells,inducing the GSH depletion and Fe2+***,the cleavage of trisulfide bond could also consume GSH,and the released DOX induces the generation of H2O2,which would react with the generated Fe2+in step one to induce efficient Fenton reaction-dependent ***,the formed Fe3+/Fe2+couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent *** iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion,ROS generation and lipid peroxidation,providing new sights for efficient cancer therapy.

关键词： Ferroptosis Iron Liposome Redox Prodrug

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Cancer-specific calcium nanoregulator suppressing the generation and circulation of circulating tumor cell clusters for enhanced anti-metastasis combinational chemotherapy

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Acta Pharmaceutica Sinica B 2021年第10期11卷 3262-3271页

作者： Dan Li Yingli Wang Chang Li Qiu Wang Bingjun Sun Haotian Zhang Zhonggui He Jin Sun department of pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China school of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related ***,circulating tumor cell(CTC)clusters play a pivotal role in tumor ***,we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin(DIG)and doxorubicin(DOX)co-encapsulated PLGA nanoparticles(CPDDs).CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic ***,CPDDs induce the accumulation of intracellular Ca^(2+) by inhibiting Na^(+)/K^(+)-ATPase,which help restrain cellecell junctions to disaggregate CTC ***,CPDDs suppress the epithelialemesenchymal transition(EMT)process,resulting in inhibiting tumor cells escape from the primary ***,the combination of DOX and DIG at a mass ratio of 5:1 synergistically induces the apoptosis of tumor *** vitro and in vivo results demonstrate that CPDDs not only effectively inhibit the generation and circulation of CTC clusters,but also precisely target and eliminate primary *** findings present a novel approach for anti-metastasis combinational chemotherapy.

关键词： Cell-cell junctions Digoxin Doxorubicin Homologous targeting Circulating tumor cell clusters Epithelial-mesenchymal transition Breast cancer Lung metastasis

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Cardioprotective effects of total and anthocyanin-rich extracts of Opuntia ficus-indica fruit on epinephrine-induced cardiac injury in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第12期14卷 514-522页

作者： Leila Safaeian Masoud Sadeghi-Dinani Zahra Haghighatian Mohammad-Bagher Fatahian Marjan Khademizadeh department of Pharmacology and Toxicology Pharmaceutical Sciences Research CenterSchool of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran department of Pharmacognosy School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran department of Pathology School of MedicineLorestan University of Medical SciencesKhorramabadIran pharmaceutical sciences Research Center School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran

Objective:To examine the effect of fruit extracts of Opuntia ficus-indica on epinephrine-induced myocardial injury in ***:Rats were pre-treated with hydroalcoholic and anthocyanin-rich extracts(250,500,and 1000 mg/kg)orally for 16 ***(2 mg/kg)was injected subcutaneously on days 15 and *** ECG,heart rate,RR interval,cardiac histopathology,and serum parameters of cardiac damage and oxidative stress were ***:Pretreatment with the hydroalcoholic and anthocyanin-rich extracts of Opuntia ficus-indica at doses of 500 and 1000 mg/kg reversed epinephrine-induced changes in ECG,heart rate,RR interval,and cardiac histopathology,and attenuated creatine phosphokinase-MB activity and malondialdehyde *** extracts at all doses diminished heart weight,lactate dehydrogenase,and aspartate aminotransferase,and also elevated total antioxidant ***,1000 mg/kg of the anthocyanin-rich extract was more effective than the hydroalcoholic ***:Supplementation with fruit extracts of Opuntia ficus-indica,especially anthocyanin-rich extract,could protect against epinephrine-induced cardiac injury in rats by alleviating electrocardiographic,biochemical,histopathological,and oxidative stress parameters,and may be used in the treatment of cardiovascular diseases.

关键词： Opuntia ficus-indica Antioxidant Cardiovascular diseases Epinephrine Cardiac injuries Lipid peroxidation

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