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A supramolecular nanoprodrug for prevention of gallstone formation

Chinese Chemical Letters 2025年第2期36卷 354-359页

作者： Xiangjun Zhang Xiaodi Yang Yan Wang Zhongping Xu Sisi Yi Tao Guo Yue Liao Xiyu Tang Jianxiang Zhang Ruibing Wang college of Pharmacy Chongqing Medical University Chongqing University Fuling Hospital Department of pharmaceutics College of PharmacyThird Military Medical University (Army Medical University) Yu-Yue Pathology Scientific Research Center State Key Laboratory of Trauma and Chemical Poisoning Third Military Medical University (Army Medical University) State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macau

Cholelithiasis affects approximately 10%-20% of the adult population globally. And cholesterol accumulation and nucleation of cholesterol crystals are commonly recognized as the primary process in the initiation and progression of gallstones. Hydroxypropyl-β-cyclodextrin(HPCD) is a supramolecular host compound that can solubilize cholesterol, potentially serving as a preventative or therapeutic agent for cholelithiasis. However, we found that the administration of HPCD treatment did not impede the formation of gallstones in mice, mainly attributed to the pre-complexation of its cavity during the transition process. Here we synthesized a prodrug of HPCD and prepared a HPCD nanoparticle(HPCD-NP), which can be transported efficiently to the gallbladder through the hepatobiliary system following an intravenous injection. In the bile, the HPCD-NP degraded into free HPCD, bound to cholesterol crystals and gallstones within the gallbladder and effectively increased cholesterol solubilization, leading to gallstones regression. Given the established safety of both HPCD and cyclodextrin-based nanoparticles in numerous animal and human studies, HPCD-NP shows considerable promise for the prevention and treatment of human cholelithiasis.

关键词： Gallstone Hepatobiliary transport Host-guest interaction Hydroxypropyl-β-cyclodextrin Solubilization

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Genome-wide CRISPR screens identify CLC-2 as a drug target for anti-herpesvirus therapy:tackling herpesvirus drug resistance

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Science China(Life Sciences) 2025年第2期68卷 515-526页

作者： Fayu Yang Nan Wei Shuo Cai Jing Liu Qingping Lan Hao Zhang Lu Shang Bo Zheng Mi Wang Yingchun Liu Lifang Zhang Chenzhong Fei Wu Tong Changlong Liu Ersheng Kuang Guangzhi Tong Feng Gu Shanghai Veterinary Research Institute Chinese Academy of Agricultural SciencesShanghai 200241China Key Laboratory of Veterinary Chemical Drugs and pharmaceutics Ministry of Agriculture and Rural AffairsShanghai 200241China State Key Laboratory for Animal Disease Control and Prevention College of Veterinary MedicineLanzhou UniversityLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730000China Institute of Human Virology Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China School of Medicine Tsinghua UniversityBeijing 100084China

The emergence of drug resistance to virus(i.e.,acyclovir(ACV)to herpesviruses)has been termed one of the common clinical issues,emphasizing the discovery of new antiviral *** address it,a genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)screening was performed in mouse haploid embryonic stem cells infected with pseudorabies virus(PRV),anα-herpesvirus causing human and pig *** results demonstrated that type 2 voltage-gated chloride channels(CLC-2)encoded by one of the identified genes,CLCN2,is a potential drug target for anti-herpesvirus ***-2 inhibitors,omeprazole(OME)and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid(DIDS),can efficiently inhibit infection of multiple herpesviruses in cellulo(i.e.,PRV,HSV and EBV),and effectively treat murine herpes simplex encephalitis(HSE).Additionally,DIDS was found to inhibit HSV-1 replication by blocking the PI3K/Akt *** importantly,both DIDS and OME were able to inhibit ACV-resistant HSV-1 strain *** study's findings suggest that targeting host-cell factors such as CLC-2 may be a promising approach to tackling herpesvirus drug *** discovery of CLC-2 as a potential drug target for anti-herpesvirus therapy provides a new direction for the development of novel antiviral agents.

关键词： herpesviruses CRISPR host-directed therapy CLC-2 DIDS

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Branched module-modified SN38 prodrug nanoassemblies for improved colorectal cancer therapy:Effectively balance efficacy and safety

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Nano Research 2025年第1期18卷 572-585页

作者： Qing Wang Shiyi Zuo Shufang Zheng Cuiyun Liu Yaqiao Li Jiayu Guo Danping Wang Shuo Wang Wenjing Wang Bowen Zhang Minglong Huang Xianbao Shi Jin Sun Zhonggui He Bingjun Sun Department of pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China School of Chemical Engineering The University of AdelaideAdelaideSA 5005Australia Department of Pharmacy The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China

The clinical utility of irinotecan is restricted by individual variability in carboxylesterase *** administration of its active metabolite,7-ethyl-10-hydroxycamptothecin(SN38),presents an appealing alternative due to its potent anti-tumor ***,the undesirable properties of SN38,such as poor water solubility and nontarget toxicity,present significant hurdles to its clinical *** nanoassemblies based on modular design strategy show promise in overcoming these challenges by enhancing drug delivery and selective *** modular design,the modification module plays a crucial role in improving the self-assembly capability of *** current studies mainly focus on using straight aliphatic chains for prodrug design,branched aliphatic chains emerge as superior alternatives warranting further *** this study,we selected 2-heptylundecanol(BAlc18)as modification module to construct an SN38 *** exquisite design,SN38-SS-BAlc18 NPs integrated prominent properties in selfassembly capability,specific activation and biocompatibility,resolving the challenges of irinotecan and SN38,ultimately demonstrating excellent anti-tumor *** exploration enriched the design theory of prodrug nanoassemblies that can effectively balance safety and colorectal anti-tumor efficacy.

关键词： irinotecan SN38 prodrug nanoassemblies disulfide bonds branched aliphatic chains

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Zwitterionic hyaluronic acid derivatives for co-delivery of both chemotherapeutic and nucleic acid drugs in breast cancer treatment

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Nano Research 2025年第1期18卷 607-617页

作者： Ruo-Lin Jiang Hui-Na Liu Yu-Fan Yang Zhi-Cheng Zhang Qi Dai Xiao-Yan Bao Lin-Jie Wu Ya-Xin Qin Xin Tan Xiao-Yan Sun Xu-Fang Ying Zhi-Qing Ben Min Han Institute of pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Radiation Oncology Key Laboratory of Cancer Prevention and InterventionThe Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang UniversityHangzhou 310058China Polytechnic institute Zhejiang UniversityHangzhou 310015China

Traditionally,hyaluronic acid has been widely used for drug delivery,but the current application bottleneck is that hyaluronic acid is hydrophilic and electronegative,which makes it difficult to carry hydrophobic drugs and small interfering RNA(siRNA)with the same *** on previous studies,we designed and synthesized hyaluronic acid nanocarriers HA-spermine/N,N,N-trimethylcystamine/DOX-TPP(HSTD)for loading siRNA to overcome the problem of siRNA release caused by strong electrostatic ***,N,N,Ntrimethylcystamine in the carrier can be degraded by intracellular glutathione to completely and rapidly release siRNA,thus promoting ***,when codelivered with the chemotherapy drug doxorubicin(DOX),this novel nanocarrier showed promising synergy in inhibiting tumor growth.

关键词： zwitterionic hyaluronic acid N N N-trimethylcystamine small interfering RNA(siRNA) doxorubicin

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Selenium-layered nanoparticles serving for oral delivery of phytomedicines with hypoglycemic activity to synergistically potentiate the antidiabetic effect

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Acta Pharmaceutica Sinica B 2019年第1期9卷 74-86页

作者： Wenji Deng Huan Wang Baojian Wun Xingwang Zhang Department of pharmaceutics College of Pharmacy Jinan University

Diabetes mellitus(DM) remains a great challenge in treatment due to pathological *** has been proven that phytomedicines and natural medicines have prominent antidiabetic effects. This work aimed to develop selenium-layered nanoparticles(SeNPs) for oral delivery of mulberry leaf and Pueraria Lobata extracts(MPE), a group of phytomedicines with significant hypoglycemic activities, to achieve a synergic antidiabetic effect. MPE-loaded SeNPs(MPE-SeNPs) were prepared through a solvent diffusion/in situ reduction technique and characterized by particle size, ζ potential, morphology,entrapment efficiency(EE) and drug loading(DL). The resulting MPE-SeNPs were 120 nm around in particle size with EE of 89.38% for rutin and 90.59% for puerarin, two marker components in MPE. MPESeNPs exhibited a slow drug release and good physiological stability in the simulated digestive *** oral administration, MPE-SeNPs produced significant hypoglycemic effects both in the normal and diabetic rats. Ex vivo intestinal imaging and cellular examinations demonstrated that MPE-SeNPs were provided with outstanding intestinal permeability and transepithelial transport aptness. It was also revealed that MPE-SeNPs could alleviate the oxidative stress, improve the pancreatic function, and promote the glucose utilization by adipocytes. Our study provides new insight into the use of integrative nanomedicine containing phytomedicines and selenium for DM treatment.

关键词： Diabetes mellitus Phytomedicine Bioavailability Hypoglycemic effect Selenium nanoparticles

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Hydrothermal Synthesis, Crystal Structure, Magnetic Properties and Network Topology of a Novel Binuclear Co(Ⅱ) Coordination Polymer_∞~1[Co_2(4,4'-bpy)_2(L)_4](bpy = Bipyridine, HL = 2-Fluorbenzoic Acid)

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Chinese Journal of Structural Chemistry 2015年第6期34卷 953-959页

作者： HU Ling-Xia ZHANG Bi-Song WU Chang-Sheng HUANG Dong-Wei QIU Jian-Ping college of pharmaceutics and Material Engineering Jinhua Polytechnic

One novel binuclear Co（Ⅱ） coordination polymer ∞ [Co2（4,4＇-bpy）2（L）4] （1, bpy = bipyridine, HL = 2-fluorbenzoic acid） has been hydrothermally synthesized and structurally characterized by elemental analysis, IR and X-ray single-crystal diffraction. Complex 1 crystallizes in the monoclinic system, space group P21/c with a = 11.163（2）, b = 21.943（4）, c = 9.6381（19） A, β = 113.92（3）°, V= 2158.2（7） A3, Z= 4, Dc = 1.518 g/cm^3, Mr = 493.31, F（000） =1004, R = 0.0303 and wR = 0.0808 for 3614 observed reflections （I〉 2σ（I））. Complex I exhibits a 3D Schlafli symbol （4.62）（4.66.83） topological framework, and the magnetic characterization shows weak antiferromagnetic coupling exchange between two Co ions.

关键词： Co(Ⅱ) complex coordination polymer crystal structure magnetic properties topological framework

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A novel Ireland-Claisen rearrangement/Diels-Alder tandem reaction of propargylic acrylates with acyclic dienophiles

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Chinese Chemical Letters 2013年第2期24卷 137-139页

作者： Yun-Xia Li Yi-Lin Sheng Bi-Song Zhang college of pharmaceutics and Material Engineering Jinhua College of Profession and Technology

Received 18 October 2012 Received in revised form 14 December 2012 Accepted 21 December 2012 Available online 29 January 2013

关键词： lreland-Claisen rearrangementDiels-Alder reactionTandem reactionPropargylic acrylates

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Pharmacokinetic interaction of Acacia catechu with CYP1A substrate theophylline in rabbits

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Journal of Traditional Chinese Medicine 2015年第5期35卷 588-593页

作者： Abdullah Mohammed AI-Mohizea Mohammad Raish Abdul Ahad Fahad Ibrahim AI-Jenoobi Mohd Aftab Alam Department of pharmaceutics College of PharmacyKing Saud University

OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in ***:In the present investigation the effect of BC on the pharmacokinetics of theophylline,a CYP1A2 substrate was *** the study,BC(264 mg/kg,p.o.) or saline(control group) was given to rabbits for 7 consecutive days and on the 8^(th)day theophylline(16 mg/kg) was administered orally one hour after BC or saline *** samples were withdrawn at different time intervals(0.5,1,1.5,2,3,4,6,8,12,24 and 36 h) from the marginal ear ***:The pretreatment of rabbits with BC resulted in a significant increase in maximum blood concentration,time of peak concentration and area under the concentration time profile curve until last observation which was about 41.32%,35.71%and 15.03%,*** decreases in clearance,volume of distribution,and half-life were *** is suggested that BC pretreatment decreases the CYP1 A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline,which may be due to inhibition of CYP1 ***:BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1 A and P-glycoprotein *** on these results,precaution should be exercised when administering BC with CYP1 A substrate.

关键词： Acacia Catechu Cytochromes Herbdrug interactions Pharmacokinetics Theophylline

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Preparation of fluconazole buccal tablet and influence of formulation expedients on its properties

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药学学报 2011年第4期46卷 460-465页

作者： MOHAMED Saifulla P MUZZAMMIL Shariff PRAMOD Kumar TM Department of pharmaceutics College of PharmacyJSS University

The aim of present study was to prepare buccal tablets of fluconazole for oral *** dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic *** buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression *** stalline cellulose was used as the filler and its effect was also *** prepared dosage forms were evaluated for physicochemical properties,in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model *** containing 50% of polymers(Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force,residence time and in vitro drug *** in vitro drug release studies revealed that drug released for 8 h,which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.

关键词： adhesion Carbopol 71G fluconazole mucoadhesive tablet Noveon AA-1 oral candidiasis

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Measurement and correlation of solubility of diosmin in four pure solvents and β-cyclodextrin solution at 298.15K to 333.15K

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Chinese Journal of Chemical Engineering 2015年第5期23卷 812-815页

作者： Md Khalid Anwer Faiyaz Shakeel Department of pharmaceutics College of Pharmacy Salman Bin Abdulaziz University Center of Excellence in Biotechnology Research King Saud University Department of pharmaceutics College of Pharmacy King Saud University

The aim of present study was to measure and correlate the solubility of poorly water-soluble flavonoid diosmin in water, ethanol, isopropyl alcohol （IPA）, polyethylene glycol-400 （PEG-400） and β-cyclodextrin （β-CD） aqueous solution （0.02 mol·L^-1 ）. The solubility of diosmio was measured using the shake flask method from （298.15 to 333.15） K at atmospheric pressure. The experimental solubilities of diosmin were regressed by the modified Apelblat model with a relative deviation in the range of 0.048% to 5.940%. The correlation coefficients were observed in the range of 0.9957 to 0.9995. The solubility of diosmin was found to be increased with temperature in all sample matrices investigated. The mole fraction solubility of diosmin was found to be higher in 5-CD aqueous solution and PEG-400 as compared to water, ethanol and IPA. Based on solubility data of present study, diosmin was considered as practically insoluble in water, insoluble in ethanol ＆ IPA and soluble in PEG- 400 and β-CD aqueous solution.

关键词： Apelblat model Cyclodextrin Diosmin Solubility Thermodynamics

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