European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Nanoformulated cannabidiol for skin disorders: A GRADE-based systematic review of therapeutic evidence and efficacy","authors":"Bakr Ahmed ,&nbsp;Simrandeep Kaur ,&nbsp;Srishti Naryal ,&nbsp;Aanchal Devi ,&nbsp;Muskan Kathpalia ,&nbsp;Rohan M. Shah ,&nbsp;Indu Pal Kaur","doi":"10.1016/j.ejpb.2025.114784","DOIUrl":"10.1016/j.ejpb.2025.114784","url":null,"abstract":"<div><div>Cannabidiol (CBD), a non-psychoactive chemical derived from <em>Cannabis sativa L</em>., has significant dermatological potential due to its antiinflammatory, antioxidant, and wound healing attributes. However, its clinical usage is limited by instability, minimal skin penetration, and poor solubility. Nanotechnology-based delivery systems such as pickering emulsions, cryogels, lipid nanoparticles, and nanomicelles have emerged as promising strategies to enhance localized skin delivery, improve penetration, enable sustained release, and reduce adverse effects. According to this analysis of 16 papers and 18 patents (2019-2024), CBD that has been nanoformulated offers improved tolerability, sustained release, and skin delivery. According to GRADE review, impacts on dermal absorption, inflammation, and wound healing demonstrated intermediate certainty, but outcomes such as skin penetration, controlled release, and safety showed high certainty. Applications for acne, psoriasis, and eczema show enhanced patient compliance and efficacy. Despite clinical and regulatory obstacles, nano-CBD platforms provide a safe, focused, and efficient approach to improving dermatological care.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114784"},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug loading mechanism of hollow hydroxyapatite microcapsules","authors":"Jonas Kost,&nbsp;Nathalie Peyer,&nbsp;Jörg Huwyler,&nbsp;Maxim Puchkov","doi":"10.1016/j.ejpb.2025.114785","DOIUrl":"10.1016/j.ejpb.2025.114785","url":null,"abstract":"<div><div>Inorganic hydroxyapatite microcapsules are innovative drug delivery devices tailored for oral drug delivery. They were designed as novel excipients, the so-called template inverted particles (TIP), to assist in preparing the orally disintegrating tablets. This study characterized the drug loading capacity using 11 clinically relevant drugs covering all BCS classes, focusing on midazolam HCl, ivermectin, ibuprofen, and metronidazole benzoate. An exceptionally high drug loading capacity of 45 % (v/v) was observed for all studied drugs. Compaction of loaded TIP resulted in mechanically stable tablets with tensile strengths of up to 6 MPa and disintegrating in a few seconds upon contact with water. Accelerated dissolution of encapsulated drugs is explained by the microcapsules’ high specific surface area and the inhibited crystallization due to spacial constraints for some tested drugs. Efficient drug loading into TIP’s internal hollow cavity structure is facilitated by a self-loading mechanism, eliminating the need for complex, drug-specific loading strategies. A mathematical model is presented to describe the self-loading mechanism of TIP, which is responsible for exclusive drug deposition within the cavity of the particles. We demonstrate that TIP, being a versatile and cost-effective platform technology, has the potential to facilitate the formulation development process of patient-friendly medicines.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114785"},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endotoxin masking in human plasma: The role of protein interactions and lipopolysaccharide structure","authors":"Luisa Burgmaier ,&nbsp;Johanna Lifka ,&nbsp;Meltem Avci-Adali ,&nbsp;Johannes Reich","doi":"10.1016/j.ejpb.2025.114786","DOIUrl":"10.1016/j.ejpb.2025.114786","url":null,"abstract":"<div><div>Reliable endotoxin detection in human plasma is compromised by masking effects, which interfere with Limulus Amebocyte Lysate (LAL)-based assays. While electrostatic interactions have been considered a major cause of masking, our study demonstrates that they alone cannot fully explain the phenomenon. We show that masking occurs rapidly in plasma, with endotoxin recoveries dropping below 50% within minutes. Although increasing the pH to 12 partially restores detection, high-salt treatments fail to disrupt endotoxin-protein complexes, indicating additional stabilizing forces. Plasma fractionation experiments revealed that specific proteins, particularly lysozyme, contribute significantly to masking, while human serum albumin plays only a minor role at physiological concentrations. Furthermore, structural differences between lipopolysaccharides (LPS) influence masking behavior: smooth LPS variants are masked more rapidly than rough mutants, suggesting that hydrophilic interactions and molecular conformation play a crucial role. Our findings highlight that endotoxin masking is not solely driven by electrostatic interactions but results from a complex interplay of structural and biochemical factors. Recognizing these mechanisms is essential for developing reliable detection strategies, ensuring the accuracy of endotoxin testing in clinical and pharmaceutical applications.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114786"},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing dicarboxylate-based salts for enhancing the performance of amorphous solid dispersions: The case of olanzapine","authors":"Afroditi Kapourani ,&nbsp;Ioannis Pantazos ,&nbsp;Stamatia Skoutida ,&nbsp;Andreana N. Assimopoulou ,&nbsp;Panagiotis Barmpalexis","doi":"10.1016/j.ejpb.2025.114782","DOIUrl":"10.1016/j.ejpb.2025.114782","url":null,"abstract":"<div><div>Previous studies have shown that the use of dicarboxylic acid salts can improve the performance of drug amorphous solid dispersions (ASDs), such as in the case of olanzapine (OLN). However, these studies focused only on the use of limited ASD matrices/carriers, e.g. polyvinyl alcohol, overlooking thus the critical impact of their selection on the drug’s physical stability and dissolution performance. This study evaluates the performance of ASDs containing fumarate (FUM) and succinate (SUC) drug salts in comparison to ASDs prepared with the drug base, by utilizing the same model drug (i.e., OLN) and various ASD matrices/carriers. Results revealed that inappropriate matrix/carrier selection, even with the more stable amorphous drug salts, led to physical instability (i.e., drug recrystallization) during long term storage. Specifically, only certain matrices/carriers, such as Soluplus® (SOL) for OLN_SUC, copovidone (PVPVA64) or hydroxypropyl cellulose (HPC-SL) for OLN_FUM, and povidone (PVP) for OLN base, were effective in preventing drug recrystallization after three months of storage. Molecular interactions, supported by differential scanning calorimetry (DSC), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and molecular dynamics (MD) simulations, demonstrated strong hydrogen bonds between OLN molecules (base and salts) and specific matrices/carriers, contributing to the system’s physical stability. Dissolution studies conducted under non-sink conditions further highlighted the importance of matrix/carrier selection for drug supersaturation, with OLN_FUM and OLN_SUC ASDs showing superior performance (higher degree of supersaturation) compared to OLN in its base form. However, all OLN_FUM formulations, as well as OLN_SUC-based ASDs with SOL, showed significant physical instability during solubilization, leading to API’s recrystallization in the precipitates collected after dissolution - a pitfall that was not observed in ASD prepared with OLN base and SOL. Hence, the obtained results highlight the necessity of extensive pre-formulation and formulation studies in the preparation of ASDs for various poorly water-soluble drugs (such as OLN) before suggesting dicarboxylate-based drug salts as a one-size-fits-all solution.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114782"},"PeriodicalIF":4.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Spray freeze drying as a novel drying process for the formulation of probiotic powders containing Lacticaseibacillus rhamnosus GG” [Eur. J. Pharm. Biopharm. 212 (2025) 114748]","authors":"A. Steegmans ,&nbsp;M. Plitzko ,&nbsp;B. Luy ,&nbsp;S. Lebeer ,&nbsp;F. Kiekens","doi":"10.1016/j.ejpb.2025.114774","DOIUrl":"10.1016/j.ejpb.2025.114774","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114774"},"PeriodicalIF":4.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compatibility of antimicrobial preservatives with therapeutic bacteriophages of the genera Pbunavirus and Kayvirus","authors":"Marie Komárková ,&nbsp;Martin Benešík ,&nbsp;Tereza Procházková ,&nbsp;Adam Vinco ,&nbsp;Monika Laichmanová ,&nbsp;Soňa Smetanová ,&nbsp;Petr Jelínek ,&nbsp;Marek Moša ,&nbsp;Tibor Botka ,&nbsp;Miroslav Šoóš ,&nbsp;Roman Pantůček","doi":"10.1016/j.ejpb.2025.114781","DOIUrl":"10.1016/j.ejpb.2025.114781","url":null,"abstract":"<div><div>Implementing bacteriophages into dosage forms is a significant step for the practical application of phage therapy. While designing a dosage form, bacteriophages as active ingredients may be exposed to excipients, guaranteeing microbial quality. However, only a few antimicrobial preservatives have been studied regarding their interaction with bacteriophages during long-term storage. Here, the stability of the staphylococcal <em>Kayvirus</em> and pseudomonal <em>Pbunavirus</em> with twelve commonly used preservatives was monitored for thirteen weeks to assess the risk of destabilisation of phage suspensions by excipients. The effectiveness of preservatives on the test bacteria, yeast and mould was determined using a microdilution method and the phage lytic activity by plaque enumeration. The antimicrobial activity of preservatives with bacteriophages was confirmed, except benzalkonium chloride and chlorhexidine digluconate, which showed precipitation and were classified as incompatible. A complete loss of phage potency in both tested phages occurred with diazolidinyl urea and in <em>Kayvirus</em> with benzalkonium chloride. For both phages, a slight decrease in titer, by one order of magnitude, was observed with m-cresol, sodium propionate, sodium benzoate, and phenylethyl alcohol. For <em>Kayvirus</em>, thimerosal, parabens, and mono propylene glycol and for <em>Pbunavirus</em>, phenoxyethanol also met the criteria. The decrease by two or more orders was determined for the remaining cases. This study helps select antimicrobial preservatives for optimizing dosage formulations with the therapeutically applicable bacteriophages.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114781"},"PeriodicalIF":4.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal delivery of platelet cell membrane-cloaked Astragaloside IV loaded biomimetic nanoparticles for enhanced therapeutics in acute lung injury mice","authors":"Yue Zhao ,&nbsp;Yinlian Yao ,&nbsp;Shilong Fan ,&nbsp;Xin Shen ,&nbsp;Jiahao Liu ,&nbsp;Xingxing Chai ,&nbsp;Xueqin Huang ,&nbsp;Hua Jin ,&nbsp;Zhikun Zhou","doi":"10.1016/j.ejpb.2025.114777","DOIUrl":"10.1016/j.ejpb.2025.114777","url":null,"abstract":"<div><div>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) frequently occur alongside sepsis, presenting significant challenges and associated mortality rates between 25 % and 40 %. Despite notable advancements in medical treatment, effective pharmacological options for ALI/ARDS remain limited due to rapid systemic clearance and insufficient targeting of lung tissues. To address this issue, we developed nanoparticles loaded with Astragaloside IV (ASIV-NPs) using an emulsification-evaporation method. Network pharmacology revealed 72 shared targets between ASIV and acute pneumonia, with core nodes (AKT1, CASP3, BCL2, IL6) identified through protein interaction analysis. Enrichment studies linked these targets to critical pathways including JAK-STAT signaling and cellular stress response. Molecular docking confirmed ASIV’s strong binding affinity (≤-5 kcal/mol) to key proteins governing inflammation and apoptosis. In vitro, PM@ASIV-NPs demonstrated biocompatibility, targeted inflamed macrophages, suppressed pro-inflammatory cytokines (IL-6, TNF-α, IL-1β), and scavenged ROS. In vivo imaging showed precise lung accumulation, while intranasal administration in ALI mice significantly enhanced IL-10, reduced inflammatory markers, and improved survival. The combined pharmacological evidence elucidates ASIV’s multimodal mechanism through target-pathway modulation, aligning with its observed therapeutic effects. This biomimetic nanoplatform utilizing platelet membrane camouflage offers a promising strategy for targeted ALI/ARDS treatment, with potential applicability to COVID-19-related pneumonia.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114777"},"PeriodicalIF":4.4,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein stability and critical stabilizers in frozen solutions","authors":"Jinghan Li ,&nbsp;Xinhao Lin ,&nbsp;Zixuan Zhen","doi":"10.1016/j.ejpb.2025.114764","DOIUrl":"10.1016/j.ejpb.2025.114764","url":null,"abstract":"<div><div>Freezing is a common unit operation during the processing and storage of therapeutic proteins. Upon freezing, protein molecules and other solutes are excluded from the ice crystals, resulting in the formation of a freeze concentrated solution (FCS). Protein destabilization can be prevented due to the low temperature and the formation of a viscous FCS. However, the changes in temperature, pH, salt concentration, and the formation of ice-solution interfaces can induce protein destabilization. The current paper reviews the stresses associated with freezing and thawing and discusses the stabilization strategies. At subambient conditions, protein unfolding is thermodynamically favored when the solution is cooled below the cold denaturation temperature. The formation of a viscous FCS, specifically at a temperature below the glass transition temperature (T_g’), immobilizes and stabilizes the proteins. Protein can adsorb at the ice/solution interface, followed by unfolding and aggregation. Therefore, freezing and thawing rates need to be carefully controlled to minimize the ice surface area (due to the formation of small ice crystals) and to avoid ice recrystallization. Besides, stabilizers, including sugars, surfactants, and amino acids, are added as stabilizers (cryoprotectants) to prevent protein destabilization upon freezing and frozen storage. <em>In situ</em> spectroscopic (infrared, Raman, and solid-state NMR) and scattering (X-ray and neutron) techniques provide useful insights into protein stability and phase transitions of excipients in frozen solutions. Finally, we discuss the importance of the freezing process and excipient selection in the successful lyophilization of protein formulations. The review paper comprehensively discusses the challenges during the cryopreservation of therapeutic proteins and provides valuable insights into the critical stabilizers in frozen protein solutions.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114764"},"PeriodicalIF":4.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Preparation and evaluation of celecoxib lyophilized orally disintegrating tablets with high bioavailability” [Eur. J. Pharm. Biopharm. 213 (2025) 114756]","authors":"Shuai Sun ,&nbsp;Mengjun Wang ,&nbsp;Jin Chen ,&nbsp;Xiaoli Ju ,&nbsp;Furong Zhang ,&nbsp;Meilin He ,&nbsp;Dongfang Cheng ,&nbsp;Shumeng Kong","doi":"10.1016/j.ejpb.2025.114760","DOIUrl":"10.1016/j.ejpb.2025.114760","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114760"},"PeriodicalIF":4.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of pH, buffers, molarity, and temperature on solution state degradation of semaglutide using LC-HRMS: A preformulation protocol for peptide drug delivery","authors":"Adarsh Malgave ,&nbsp;Sideequl Akbar ,&nbsp;Anumol Joseph ,&nbsp;Dande Aishwarya ,&nbsp;Ramalingam Peraman ,&nbsp;Rajkumar Malayandi","doi":"10.1016/j.ejpb.2025.114780","DOIUrl":"10.1016/j.ejpb.2025.114780","url":null,"abstract":"<div><div>Semaglutide (SGL), a long-acting GLP-1 (Glucagon-like peptide) receptor agonist, is a 31-amino acid peptide modified with a C18 fatty diacid for albumin binding. Peptides are fragile and susceptible to degradation during formulation, storage, and transportation. The degradation of peptides resulted in the formation of impurities that may impact safety, efficacy, immunogenicity, and regulatory compliance. The present study examines the effects of pH, temperature, buffer species, and molarity on the stability of SGL. Reverse-phase ultra-performance liquid chromatography (RP-UPLC) was used to separate impurities, followed by liquid chromatography high-resolution mass spectrometry (LC-HRMS) for their molecular weight. The stress stability studies were conducted in thermal stress conditions at 25 °C, 40 °C, 60 °C (for 28 days), and 80 °C (for 7 days). The influence of pH, buffer strength, and buffer species on the degradation of SGL was investigated at 25 °C and 40 °C. The degradation of SGL resulted in thirteen known impurities, and their fragments were identified using LC-MS analysis. Six impurities, such as impurity 4 (<em>m</em>/<em>z</em> = 2717.21), impurity 5 (<em>m</em>/<em>z</em> = 4129.64), impurity 7 (<em>m</em>/<em>z</em> = 3762.28), impurity 8 (<em>m</em>/<em>z</em> = 3456.94), impurity 12 (<em>m</em>/<em>z</em> = 2967.5), and impurity 13 (<em>m</em>/<em>z</em> = 839), were formed across all the testing conditions. These impurities were relatively stable when compared to other formed impurities. The influence of pH on the thermal stability of SGL was demonstrated. The impurities, such as impurity 2 (<em>m</em>/<em>z</em> = 845.13), impurity 9 (<em>m</em>/<em>z</em> = 3397.76), impurity 10 (<em>m</em>/<em>z</em> = 701.0), and impurity 11 (<em>m</em>/<em>z</em> = 4125.7), were absent across all pH conditions, but these impurities were found when water was used as a solvent. The study demonstrated that the pH was a key factor for the thermal degradation of SGL. The degradation pathways were elucidated based on the mass data for known masses. The solution-state thermal stress studies were performed to select the buffer for formulating long-acting PLGA formulations. Moreover, the solution state stress stability data could be helpful for optimization of the pharmaceutical process, in vivo stability of SGL in muscles, storage and transportation of finished products, and determining the shelf-life.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114780"},"PeriodicalIF":4.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}