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Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system:the relationship of hydrogen bonding strength and controlled release capacity

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Acta Pharmaceutica Sinica B 2020年第5期10卷 928-945页

作者： Zheng Luo Chao Liu Peng Quan Degong Yang Hanqing Zhao Xiaocao Wan Liang Fang department of pharmaceutical Sciences School of PharmacyShenyang Pharmaceutical Universityshenyang 110016China

Background:Hydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal ***,the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported,and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive(PSA)was not well *** present study shed light on this ***:Acrylate PSAs with amide group were synthesized by a free radical-initiated solution *** drugs,i.e.,etodolac,ketoprofen,gemfibrozil,zolmitriptan,propranolol and lidocaine,were selected as model *** vitro drug release and skin permeation experiments and in vivo pharmacokinetic experiment were *** correlation analysis,fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA *** test,rheology study,and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of ***:Release rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations;however,only zolmitriptan and propranolol showed decreased skin permeation *** was found that drug release was controlled by amide group through hydrogen bonding,and controlled release extent was positively correlated with hydrogen bonding ***:From these results,we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.

关键词： Controlled release Polar functional group Hydrogen bonding strength Pharmacokinetics Pressure sensitive adhesive Hydrogen bonding interaction Transdermal patch Stratum corneum

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Determination of cefcapene acid by LC-MS and their application to a pharmacokinetic study in healthy Chinese volunteers

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Journal of pharmaceutical analysis 2013年第2期3卷 84-92页

作者： Hong-Fei Duan Li Ding Xiao-Bing Li Lin-Lin Hu Ai-Dong Wen Ye Leng Zhen Liu department of pharmaceutical analysis China Pharmaceutical University24 Tongjiaxiang department of pharmacy The First Affiliated Hospital of the Fourth Military Medical University of PLA

Simple,rapid and specific liquid chromatography-mass spectrometry（LC-MS） methods have been developed and validated for the quantification of cefcapene acid in human plasma and *** samples were simply pretreated with methanol for *** samples were briefly diluted with methanol-water（50：50,v/v）,and centrifuged to remove large *** separation was performed on a Hedera ODS-2 *** the plasma assay,the isocratic mobile phase consisted of 35% solvent A（Methanol） and 65% solvent B（10 mM ammonium acetate buffer solution containing 0.2% folic acid） with a flow rate of 0.3 mL/*** the urine assay,the isocratic mobile phase consisted of 30% solvent A（Methanol） and 70% solvent B（10 mM ammonium acetate buffer solution containing 0.2% folic acid） with a flow rate of 0.3 mL/*** assays were linear over the concentration ranges of 0.03-5 μg/mL in plasma and 0.1-400 μg/mL in urine,and were successfully applied to a pharmacokinetic study after single and multiple oral administrations of cefcapene pivoxil hydrochloride tablets in healthy Chinese volunteers.

关键词： Cefcapene acid Cefcapene pivoxil LC-MS Human plasma Urine Pharmacokinetics

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Simultaneous quantitation of folic acid and 5-methyltetrahydrofolic acid in human plasma by HPLC–MS/MS and its application to a pharmacokinetic study

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Journal of pharmaceutical analysis 2015年第4期5卷 269-275页

作者： Xiao-Hong Zheng Li-Yuan Jiang Lan-Ting Zhao Quan-Ying Zhang Li Ding department of pharmaceutical analysis China Pharmaceutical University Medical Faculty Quzhou College of Technology department of pharmacy The Second Affiliated Hospital of Soochow University

A sensitive method based on high-performance liquid chromatography-tandem mass spectrometry （LC- MS/MS） has been developed for the simultaneous determination of folic acid （FA） and its active meta- bolite, 5-methyltetrahydrofolic acid （5-M-THF）, in human plasma. The analytes were extracted from plasma with methanol solution containing 10 mg/mL of 2-mercaptoethanol and 0.025% （v/v） ammonium hydroxide. FA and 5-M-THF were more stable after the addition of 2-mercaptoethanol and ammonium hydroxide in the sample preparation procedures of this study than they were in the previously published methods. Chromatographic separation was performed on a Hedera ODS-2 column using a gradient elution system of acetonitrile and 1 mM ammonium acetate buffer solution containing 0.6% formic acid as mobile phase. LC-MS/MS was carried out with an ESI ion-source and operated in the multiple reaction monitoring （MRM） mode. The assay was linear over the concentration ranges of 0.249-19.9 ng/mL for FA, and 5.05-50.5 ng/mL for 5-M-THF. The developed LC-MS/MS method offers increased sensitivity for quantification of FA and 5-M-THF in human plasma and was applicable to a pharmacokinetic study of FA and 5-M-THF.

关键词： Folic acid 5-Methyltetrahydrofolic acid 2-Mercaptoethanol LC-MS/MS Pharmacokinetics

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Precolumn derivatization LC-MS/MS method for the determination and pharmacokinetic study of glucosamine in human plasma and urine

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Journal of pharmaceutical analysis 2012年第1期2卷 19-28页

作者： Min Songa, Tai-Jun Hanga, Cheng Wanga, Lin Yangb, Ai-Dong Wenb adepartment of pharmaceutical analysis, China pharmaceutical University, Nanjing 210009, China bdepartment of pharmacy, Xijing Hospital, Xi’an 710032, China department of pharmaceutical analysis China Pharmaceutical University Nanjing 210009 China. department of pharmacy Xijing Hospital Xi'an 710032 China.

A selective precolumn derivatization liquid chromatography–tandem mass spectrometric (LC–MS/MS) method for the determination of glucosamine in human plasma and urine has been developed and validated. Glucosamine was derivatized by o-phthalaldehyde/3-mercaptopropionic acid. Chromatographic separation was performed on a Phenomenex ODS column (150 mm 4.6 mm, 5 mm) using linear gradient elution by a mobile phase consisting of methanol (A), and an aqueous solution containing 0.2% ammonium acetate and 0.1% formic acid (B) at a flow rate of 1 mL/min. Tolterodine tartrate was used as the internal standard (IS). With protein precipitation by acetonitrile and then the simple one-step derivatization, a sensitive bio-assay was achieved with the lower limit of quantitation (LLOQ) as low as 12 ng/mL for plasma. The standard addition calibration curves suitable for clinical sample analysis showed good linearity over the range of 0.012–8.27 mg/mL in plasma and 1.80–84.1 mg/mL in urine. The fully validated method has been successfully applied to a pharmacokinetic study of compound glucosamine sulfate dispersible tablets in health Chinese volunteers receiving single oral doses at 500, 1000 and 1500 mg of glucosamine sulfate, as well as multiple oral doses of 500 mg t.i.d. for 7 consecutive days.

关键词： Glucosamine Pharmacokinetics Precolumn derivatization LC–MS/MS

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A facile phototheranostic nanoplatform integrating NIR-Ⅱ fluorescence/PA bimodal imaging and image-guided surgery/PTT combinational therapy for improved antitumor efcacy

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Journal of Materials Science & Technology 2022年第35期130卷 208-218页

作者： Xiuping Han Wenyou Fang Tianqi Zhang Xuan Zhong Kun Qian Zhitao Jiang Rongfeng Hu Guoqiang Shao Lei Zhang Qing Zhang department of Pharmaceutics and Key Laboratory of Cardiovascular&Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China State Key Laboratory of Organic Electronics and Information Displays&Institute of Advanced Materials(IAM) Nanjing University of Posts&TelecommunicationsNanjing 210023China department of nuclear Medicine Nanjing First HospitalNanjing Medical UniversityNanjing 211166China Anhui Province Key Laboratory of pharmaceutical Preparation Technology and Application Anhui Province Engineering Technology Research Center of Modern Pharmaceutical PreparationAnhui University of Chinese MedicineHefei 230012China department of nuclear Medicine Taizhou People’s HospitalNanjing University of Chinese MedicineTaizhou 225300China Center for Molecular Imaging Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

Phototheranostic with highly integrated functions is an attractive platform for cancer management. It remains challenging to develop a facile phototheranostic platform with complementary bimodal imaging and combinational therapy capacity. Herein, the small-molecule cyanine IR780 loaded liposomes have been harnessed as a nanoplatform to simultaneously realize photoacoustic(PA)/the second near-infrared window(NIR-Ⅱ) fluorescence imaging and image-guided surgery/adjuvant photothermal therapy(PTT).This nanoplatform exhibits attractive properties like uniform controllable size, stable dispersibility, NIR-Ⅱ fluorescence emission, photothermal conversion, and biocompatibility. Benefiting from the complementary PA/NIR-Ⅱ fluorescence bimodal imaging, this nanoplatform was successfully applied in precise vasculature delineation and tumor diagnosis. Interestingly, the tumor was clearly detected by NIR-Ⅱ fluorescence imaging with the highest tumor-to-normal-tissue ratio up to 12.69, while signal interference from the liver was significantly reduced, due to the difference in the elimination rate of the nanoplatform in the liver and tumor. Under the precise guidance of the image, the tumor was accurately resected, and the simulated residual lesion after surgery was completely ablated by adjuvant PTT. This combined therapy showed improved antitumor efcacy over the individual surgery or PTT. This work develops a facile phototheranostic nanoplatform with great significance in accurately diagnosing and effectively treating tumors using simple NIR light irradiation.

关键词： NIR-Ⅱfluorescence imaging Photoacoustic imaging Image-guided surgery Adjuvant photothermal therapy Phototheranostics

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PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α-GLUT2 pathway

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2391-2405页

作者： Peihua Liu Ling Jiang Weimin Kong Qiushi Xie Ping Li Xiaonan Liu Jiayi Zhang Ming Liu Zhongjian Wang Liang Zhu Hanyu Yang Ying Zhou Jianjun Zou Xiaodong Liu Li Liu Center of Drug Metabolism and Pharmacokinetics School of PharmacyChina Pharmaceutical UniversityNanjing 210009China Jiangsu Key Laboratory of New Drug Research and Clinical pharmacy Xuzhou Medical UniversityXuzhou 221004China department of Clinical Pharmacology Nanjing First HospitalNanjing Medical UniversityNanjing 210006China

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor(PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha(HNF4 a)-glucose transporter 2(GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4 a expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4 a expression, while silencing PXR upregulated HNF4 a and GLUT2 *** HNF4 a decreased GLUT2 expression, while overexpressing HNF4 a increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4 a reversed the atorvastatininduced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4 a mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4 a downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4 a plasmid increased Slc2 a2 promoter activity. Hnf4 a silencing or pregnenolone-16 a-carbonitrile(PCN) suppressed the Slc2 a2 promoter activity by decreasing HNF4 a recruitment to the Slc2 a2 promoter. Liver-specific Hnf4 a deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4 a and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4 aGLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.

关键词： Pregnane X receptor Hepatocyte nuclear factor4-alpha Glucose transporter 2 Hepatic glucose uptake Diabetes Drug-induced hyperglycemia

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Rapid fabrication of zwitterionic sulfobetaine vinylimidazole-based monoliths via photoinitiated copolymerization for hydrophilic interaction chromatography

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Journal of pharmaceutical analysis 2022年第5期12卷 783-790页

作者： Qiqin Wang Lingjue Sun Huihui Wu Ning Deng Xianglong Zhao Jingwei Zhou Tingting Zhang Hai Han Zhengjin Jiang Institute of pharmaceutical analysis College of PharmacyJinan UniversityGuangzhou510632China Anhui Prevention and Treatment Center for Occupational Disease Anhui No.2 Provincial People's HospitalHefei230041China Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education Lab of BiochemistryCollege of ChemistryXiangtan UniversityXiangtanHunan411105China department of pharmacy and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine&New Drug Research Jinan UniversityGuangzhou510632China

Zwitterionic sulfobetaine-based monolithic stationary phases have attracted increasing attention for their use in hydrophilic interaction *** this study,a novel hydrophilic polymeric monolith was fabricated through photo-initiated copolymerization of 3-(3-vinyl-1-imidazolio)-1-propanesulfonate(SBVI)with pentaerythritol triacrylate using methanol and tetrahydrofuran as the porogenic ***,the duration for the preparation of this novel monolith was as little as 5 min,which was significantly shorter than that required for previously reported sulfobetaine-based monoliths prepared via conventional thermally initiated ***,these monoliths showed good morphology,permeability,porosity(62.4%),mechanical strength(over 15 MPa),column efficiency(51,230 plates/m),and reproducibility(relative standard deviations for all analytes were lower than 4.6%).Mechanistic studies indicated that strong hydrophilic and negative electrostatic interactions might be responsible for the retention of polar analytes on the zwitterionic SBVI-based *** particular,the resulting monolith exhibited good anti-protein adhesion ability and low nonspecific protein *** excellent features seem to favor its application in ***,the novel zwitterionic sulfobetaine-based monolith was successfully employed for the highly selective separation of small bioactive compounds and the efficient enrichment of N-glycopeptides from complex *** this study,we prepared a novel zwitterionic sulfobetaine-based monolith with good performance and developed a simpler and faster method for preparation of zwitterionic monoliths.

关键词： Zwitterionic monolith Sulfobetaine Photo-initiated copolymerization Hydrophilic interaction chromatography Complex sample

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Liposomal remdesivir inhalation solution for targeted lung delivery as a novel therapeutic approach for COVID-19

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Asian Journal of pharmaceutical Sciences 2021年第6期16卷 772-783页

作者： Jingjing Li Kai Zhang Di Wua Lianjie Ren Xinyu Chu Chao Qin Xiaopeng Han Taijun Hang Yungen Xu Lei Yang Lifang Yina Jiangsu Province Engineering Research Center for R&D and Evaluation of Intelligent Drugs and Key Functional Excipients China Pharmaceutical UniversityNanjing 210009China department of pharmaceutical analysis School of PharmacyChina Pharmaceutical UniversityNanjing 210009China department of Medicinal Chemistry School of PharmacyChina Pharmaceutical UniversityNanjing 210009China

Strong infectivity enables coronavirus disease 2019(COVID-19)to rage throughout the ***,the lack of drugs with definite therapeutic effects further aggravates the spread of the *** is one of the most promising anti-severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)***,the limited clinical effects make its therapeutic effect controversial,which may result from the poor accumulation and activation of remdesivir in the ***,we developed lyophilized remdesivir liposomes(Rdv-lips)which can be reconstituted as liposomal aerosol for pulmonary delivery to improve the in vivo behavior of existing remdesivir cyclodextrin conclusion compound(Rdv-cyc)*** encapsulation endowed remdesivir with much higher solubility and better *** in vitro liposomal aerosol characterization demonstrated that Rdv-lips possessed a mass median aerodynamic diameter of 4.118μm and fine particle fraction(<5μm)higher than 50%,indicating good pulmonary delivery *** to the Rdv-cyc intravenous injection group,the Rdv-lips inhalation group displayed a nearly 100-fold increase in the remdesivir-active metabolite nucleotide triphosphate(NTP)concentration and better NTP accumulation in the lung than the Rdv-cyc inhalation group.A faster transition from remdesivir to NTP of Rdv-lips(inhalation)could also be observed due to better cell *** to other preparations,the superiority of Rdv-lips was further evidenced by the results of an in vivo safety study,with little possibility of inducing *** conclusion,Rdv-lips for pulmonary delivery will be a potent formulation to improve the in vivo behavior of remdesivir and exert better therapeutic effects in COVID-19 treatment.

关键词： COVID-19 Remdesivir Pulmonary delivery Liposomal aerosol Nucleotide triphosphate

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MXene‑Graphene Composites:A Perspective on Biomedical Potentials

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Nano-Micro Letters 2022年第8期14卷 112-123页

作者： Ebrahim Mostafavi Siavash Iravani Stanford Cardiovascular Institute Stanford University School of MedicineStanfordCA 94305USA department of Medicine Stanford University School of MedicineStanfordCA 94305USA Faculty of pharmacy and pharmaceutical Sciences Isfahan University of Medical SciencesIsfahanIran

MXenes,transition metal carbides and nitrides with graphene-like structures,have received considerable attention since their first *** the other hand,Graphene has been extensively used in biomedical and medicinal *** and graphene,both as promising candidates of two-dimensional materials,have shown to possess high potential in future biomedical applications due to their unique physicochemical properties such as superior electrical conductivity,high biocompatibility,large surface area,optical and magnetic features,and extraordinary thermal and mechanical *** special structural,functional,and biological characteristics suggest that the hybrid/composite structure of MXene and graphene would be able to meet many unmet needs in different fields;particularly in medicine and biomedical engineering,where high-performance mechanical,electrical,thermal,magnetic,and optical requirements are ***,the hybridization and surface functionalization should be further explored to obtain biocompatible composites/platforms with unique physicochemical properties,high stability,and *** addition,toxicological and long-term biosafety assessments and clinical translation evaluations should be given high priority in *** very limited studies have revealed the excellent potentials of MXene/graphene in biomedicine,the next steps should be toward the extensive research and detailed analysis in optimizing the properties and improving their functionality with a clinical and industrial ***,different synthesis/fabrication methods and performances of MXene/graphene composites are discussed for potential biomedical *** potential toxicological effects of these composites on human cells and tissues are also covered,and future perspectives toward more successful translational applications are *** current state-of-the-art biotechnological advances in the use of MXene-Graphene composites,as wel

关键词： Graphene MXene Composites Hybrid structures Biocompatibility Cancer theranostics Biomedical engineering

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Structural Aspects of Monomeric Platinum Coordination Complexes

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Materials Sciences and Applications 2014年第8期5卷 512-547页

作者： Milan Melník Peter Mikus department of pharmaceutical analysis and nuclear pharmacy Faculty of PharmacyComenius University in BratislavaBratislavaSlovak Republic

This review covers structural parameters of almost two thousand monomeric Pt coordination complexes. The Pt is found in the oxidation states zero, +1, +2, +3 and +4, from which oxidation state +2 by far prevails. There is a wide variety of donor atom ligands from uni-, bi-, ter- and tetradentate with over seventeen types of donor atoms, from which by far prevails P and N donor ligands and chlorine atom. The Pt(0) atoms are two-, three- and four-coordinated;Pt(I) and Pt(III) are only four-coordinated, Pt(II) are four- and five-coordinated, and Pt(IV) are five- and six-coor-dinated. About 10% of these complexes exist as isomers. Included are distortion (65%), cis-trans (30%), mixed isomers and ligand isomerism. The structural parameters are discussed in terms of the coordination about the platinum atom, and correlations are drawn between donor atom, bond length and interbond angles with attention to any trans-effect.

关键词： Structure Platinum Monomeric Isomers Trans-Effect

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