RSC Pharmaceutics最新文献

{"title":"Elucidation of processing parameters for the reverse engineering of tablets","authors":"Devendra Choudhary, Dnyaneshwar Kalyane, Suryanarayana Polaka, Tanisha Gupta and Rakesh Kumar Tekade","doi":"10.1039/D3PM00058C","DOIUrl":"https://doi.org/10.1039/D3PM00058C","url":null,"abstract":"<p >Reverse engineering can assist in decoding the formula and manufacturing parameters employed in innovator formulations. Generic pharmaceutical industries use it to develop generic cheaper versions of innovator tablets. Herein, we report the systematic application of reverse engineering in determining the manufacturing process utilized by innovators to prepare tablet formulations. The outcome inferred that the critical information such as the granulation and solvent type in the innovator formulation could be identified by systematic analysis <em>via</em> scanning electron microscopy (SEM) images and sieve and texture analysis. Furthermore, critical investigation of the levels of fines generated during sieve analysis could reveal the tablet manufacturing process. It was observed that the maximum amount of fines was generated in the case of post-compression granules obtained by tablets prepared by direct compression. The hardness of granules is yet another major factor that could help to delineate the type of drying technique used in innovator manufacturing. Granules obtained from crushing a tablet prepared by wet granulation with tray drying were harder than those prepared by drying on a fluidized bed dryer (FBD). The outcome of this investigation may be helpful for formulation scientists working on the development of generic formulations.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 333-343"},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d3pm00058c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of drug permeation across skin through stratum corneum ablation","authors":"Ayyah Abdoh, David Liu and Yousuf Mohammed","doi":"10.1039/D4PM00089G","DOIUrl":"https://doi.org/10.1039/D4PM00089G","url":null,"abstract":"<p >The presence of the uppermost layer of the skin, referred to as the stratum corneum (SC), restricts the therapeutic efficacy of many drugs by acting as a barrier for drug molecules. Consequently, only a small number of molecules are likely to reach the intended target region. To overcome this impediment, transdermal drug delivery (TDD) that ablates the SC was developed, resulting in the formation of micropores that develop in a defined region of the skin's outer layer, which facilitates the delivery of extremely hydrophilic medications and macromolecules throughout the skin. The process of SC ablation involves the use of a range of physical techniques, which may be categorized as element-based heating, radiofrequency, laser, and suction ablation. Lately, there has been an increasing fascination with using physical ablative methods for skin treatment. Studies have shown that using ablative methods to improve drug delivery has many benefits, such as higher bioavailability, shorter treatment duration, and rapid recovery of the skin barrier. This review presents a comprehensive overview of the principles underlying a variety of methods for SC ablation, focusing on their potential for dramatically increasing skin absorption of drug molecules, delivering vaccines as a non-invasive alternative to injections, facilitating the delivery of macromolecules, and their application in drug delivery for chronic diseases like Alzheimer's disease or diabetes mellitus. In addition, we summarize some previous studies that compared the effectiveness of various SC ablation methods.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 151-160"},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00089g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-theranostic gold nanorod-based NIR-responsive nanomedicine for the delivery of TLR7/8 adjuvant-induced effective anticancer therapy","authors":"Karunanidhi Gowsalya, Babu Rithisa, Selvaraj Shyamsivappan and Raju Vivek","doi":"10.1039/D4PM00033A","DOIUrl":"https://doi.org/10.1039/D4PM00033A","url":null,"abstract":"<p >Presently, there are several challenges that need to be overcome in the development of treatments that can effectively inhibit tumor growth, prevent the spread of tumor metastases, and protect the host against recurrence. Accordingly, a powerful synergistic immunotherapy method was developed to achieve the treatment of cancer. Herein, we established an improvement in the nanoengineering of gold nanorod (GNR)-mediated photothermal therapy (PTT) with theranostic indocyanine green (ICG), which also produced heat for effective PTT under near-infrared (NIR) light. Furthermore, co-encapsulated resiquimod (R848) induced the activation of an immune response against the tumor. In addition, a nuclear-targeted transactivator of transcription (TAT) peptide conjugated with FA-functionalized GNRs was produced for intranuclear tumor-targeted <em>in vivo</em> photothermal therapeutic efficacy, inducing DAMPs for immunogenic cell death (ICD). Post-PTT release of R848-activated TLR7/8 is essential for the development of a potent antitumor immune response by increasing the number of T cells, which recognize and kill tumors. Thus, this integrated immunotherapy method can be utilized for both the diagnosis and treatment of tumor recurrence, providing novel opportunities for both basic and clinical research. Collectively, our findings suggest that nanotechnology may be a useful technique for improving the efficacy of vaccine-based cancer immunotherapy.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 441-457"},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00033a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic mucus barrier arrays as a nanoparticle formulation screening platform†","authors":"Harry Zou, Allison Boboltz, Yahya Cheema, Daniel Song, Devorah Cahn and Gregg A. Duncan","doi":"10.1039/D3PM00057E","DOIUrl":"https://doi.org/10.1039/D3PM00057E","url":null,"abstract":"<p >A mucus gel layer lines the luminal surface of tissues throughout the body to protect them from infectious agents and particulates. As a result, nanoparticle drug delivery systems delivered to these sites may become trapped in mucus and subsequently cleared before they can reach target cells. As such, optimizing the properties of nanoparticle delivery vehicles, such as their surface chemistry and size, is essential to improving their penetration through the mucus barrier. In previous work, we developed a mucin-based hydrogel that has viscoelastic properties like that of native mucus which can be further tailored to mimic specific mucosal tissues and disease states. Using this biomimetic hydrogel system, a 3D-printed array containing synthetic mucus barriers was created that is compatible with a 96-well plate enabling its use as a high-throughput screening platform for nanoparticle drug delivery applications. To validate this system, we evaluated several established design parameters to determine their impact on nanoparticle penetration through synthetic mucus barriers. Consistent with the literature, we found nanoparticles of smaller size and coated with a protective PEG layer more efficiently penetrated through synthetic mucus barriers. In addition, we evaluated a mucolytic (tris(2-carboxyethyl) phosphine, TCEP) for use as a permeation enhancer for mucosal drug delivery. In comparison to <em>N</em>-acetyl cysteine (NAC), we found TCEP significantly improved nanoparticle penetration through a disease-like synthetic mucus barrier. Overall, our results establish a new high-throughput screening approach using synthetic mucus barrier arrays to identify promising nanoparticle formulation strategies for drug delivery to mucosal tissues.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 218-226"},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d3pm00057e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introducing RSC Pharmaceutics","authors":"Yvonne Perrie","doi":"10.1039/D4PM90001D","DOIUrl":"https://doi.org/10.1039/D4PM90001D","url":null,"abstract":"<p >A graphical abstract is available for this content</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 1","pages":" 8-8"},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm90001d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140606213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A model binary system for the evaluation of novel ion pair formulations of diclofenac","authors":"Mignon Cristofoli, Jonathan Hadgraft, Majella E. Lane and Bruno C. Sil","doi":"10.1039/D4PM00063C","DOIUrl":"https://doi.org/10.1039/D4PM00063C","url":null,"abstract":"<p >Diclofenac (DF) is well established as a topical treatment option for conditions such as osteoarthritis. In investigating novel DF ion pairs for topical delivery, studies to determine the impact of various amino acids on the distribution of DF between octanol and aqueous environments were conducted. These studies identified the amino acid <small>L</small>-histidine hydrochloride monohydrate (LHSS) as an ion pair candidate for diclofenac sodium (DNa). Preliminary porcine skin permeation studies indicated that the addition of LHSS to DNa solutions increased the amount of DF that permeated through porcine skin. With increasing amounts of LHSS added, greater amounts of DF precipitated out of solution. In the present work, the solubility of DNa in various solvents was assessed, with the intention of identifying solvents in which DNa was most soluble. Binary systems comprising water and selected solvents were tested for both miscibility and the solubility of DNa and LHSS. The model system selected to evaluate novel ion pair formulations using porcine skin <em>in vitro</em> permeation studies under finite dose (10 μL) conditions comprised Transcutol® (TC) and water. The tested formulations contained DNa at concentrations of 5, 7.5 and 10 mg mL<small>⁻¹</small>. Higher LHSS concentrations were possible when the DNa concentrations were lower, and ranged from 10–25 mg mL<small>⁻¹</small>. However, increasing the DNa concentration to 10 mg mL<small>⁻¹</small>, without adding LHSS, resulted in a significant reduction in the amount of DF that partitioned and permeated, relative to formulations that contained either 5 mg mL<small>⁻¹</small> DNa in combination with LHSS (at 12.5 or 25 mg mL<small>⁻¹</small>), or 7.5 mg mL<small>⁻¹</small> DNa together with 12.5 mg mL<small>⁻¹</small> LHSS. The current work confirms previous investigations, suggesting that the addition of LHSS to DNa in a formulation may increase the partition and permeation of DF.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 234-244"},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00063c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is receptor mediated active macrophage targeting of amphotericin B nanoformulations a promising approach?","authors":"Saugandha Das, Pooja Todke, Manisha Madkaikar and Padma Devarajan","doi":"10.1039/D4PM00023D","DOIUrl":"https://doi.org/10.1039/D4PM00023D","url":null,"abstract":"<p >We present an AmB-LIPOMER anchored with Acemannan (ACEM), a mannose ligand for active macrophage targeting, <em>via</em> mannose receptor mediated endocytosis (RME). The AmB-LIPOMER prepared by modified nanoprecipitation was anchored with ACEM by simple incubation. FITC was added to obtain fluorescent LIPOMERs. The LIPOMERs revealed a spherical morphology, an average size of 400–450 nm and a PDI &lt; 0.3. Reduction in the zeta potential and FTIR confirmed ACEM anchoring. Flow cytometry demonstrated a &gt;13-fold enhancement of the FITC-ACEM LIPOMER <em>in vitro</em> in RAW 264.7 macrophage cells, compared to the FITC-LIPOMER, ascribed to mannose receptor mediated endocytosis. This was confirmed by the decreased uptake of the FITC-ACEM LIPOMER in the mannose receptor blocking study. Nevertheless, we were surprised by an ∼2-fold decrease in the <em>in vitro</em> antileishmanial efficacy despite the augmented uptake of the ACEM LIPOMER. This poor efficacy was explained by the extensive localization of the FITC-ACEM LIPOMER in the lysosomal compartment, established by confocal microscopy, wherein AmB underwent rapid degradation. On the other hand phagocytic uptake and lipid mediated prolonged localization in the less harsh phagosome enabling lower degradation could have facilitated higher efficacy of the AmB-LIPOMER. The pharmacokinetic and biodistribution studies in rats revealed rapid and high reticuloendothelial system uptake. While the AmB-LIPOMER group exhibited no mortality, the mortality of 5 out of 6 animals in the AmB-ACEM LIPOMER group, within 15–30 minutes caused by lung necrosis was disturbing. While we propose an explanation for the toxicity, our study questions the rationale and safety of active targeting AmB using receptor mediated endocytosis.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 430-440"},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00023d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances of cassava starch-based composites in novel and conventional drug delivery systems: a state-of-the-art review","authors":"Sanjoy Das, Malay K. Das, Taison Jamatia, Bireswar Bhattacharya, Rishav Mazumder, Pradip Kumar Yadav, Nayan Ranjan Ghose Bishwas, Trinayan Deka, Dhritiman Roy, Bibek Sinha, Biplajit Das, Ichu Daule, Kishan Paul, Ankita Roy, Ankita Choudhury, Pinkan Sadhukhan, Dibyojyoti Sarmah, Dhritiman Bhargab, Bani Kumar Jana, Dubom Tayeng, Nilayan Guha, Bhrigumani Kalita and Subhajit Mandal","doi":"10.1039/D3PM00008G","DOIUrl":"https://doi.org/10.1039/D3PM00008G","url":null,"abstract":"<p >Starch has emerged as a new attractive biopolymer for use in pharmaceutical applications, owing to its distinctive physical, chemical and functional properties. This biopolymer has several potential advantages: it is biocompatible, low cost, non-toxic and easily isolated from plant sources. In the pharmaceutical field, starch is used as a raw material for developing various drug delivery platforms. Generally, cassava starch (tapioca) is obtained from the swollen roots of the perennial shrub <em>Manihot esculenta</em> and it contains a low amount of amylose in contrast to other varieties of starches. Because of this reason, cassava starch exhibits various prime benefits, including a low gelatinization temperature, higher swelling power and a relatively high viscosity paste, making it a preferable excipient for pharmaceutical applications. However, cassava starches in their native form are not effective for many applications because of their inefficiency in handling various processing requirements like high temperature and diverse pH. Their applicability can be enhanced by starch modification. These functional starches have demonstrated outstanding prospects as primary excipients in many pharmaceutical formulations. In this article, we discuss the potential application of cassava starches in the pharmaceutical and biomedical fields, along with the toxicity assessment of modified cassava starches.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 182-203"},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d3pm00008g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenylboronic acid-derived nanovectors for gene/drug delivery by targeting cell surface glycans","authors":"Venkanna Muripiti, Venkatesh Ravula, Srinivas Batthula, Janardhan Banothu and Ramesh Gondru","doi":"10.1039/D4PM00005F","DOIUrl":"https://doi.org/10.1039/D4PM00005F","url":null,"abstract":"<p >Gene mutations within cells can lead to cancer, a global health challenge affecting millions worldwide. In combating cancer, various treatments such as surgery, radiotherapy, and chemotherapy have been employed. However, the distinct underlying genetic abnormalities causing the cancer are sometimes not addressed by conventional treatments. Adding to these obstacles, targeted therapy is another continuing challenge in cancer treatment. According to recent reports, phenylboronic acid (PBA)-decorated nanoparticles efficiently transfer genes to the intended location due to their strong affinity for sialic acid (SA), which is typically overexpressed in cancerous cells. These PBA-decorated nanoparticles may connect to cancer cells specifically, which enables them to target and deliver the cargo to cancer cells. Therefore, the present review concentrates on the role of PBA-decorated nanoparticles in gene/drug delivery. It includes a discussion on various boronic acid (BA)-conjugated macromolecules. We begin with an exploration of the chemistry underlying BA and its utility in effective delivery. Furthermore, the review elaborates on its application as a targeting ligand, providing a promising avenue for more precise and effective cancer treatment strategies.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 403-411"},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d4pm00005f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green synthesis of silver nanoparticles using Phyllanthus emblica extract: investigation of antibacterial activity and biocompatibility in vivo†","authors":"Md Monir Hossain, Amir Hamza, Shakil Ahmed Polash, Mehedi Hasan Tushar, Masato Takikawa, Anuj Bhowmik Piash, Chaitali Dekiwadia, Tanushree Saha, Shinji Takeoka and Satya Ranjan Sarker","doi":"10.1039/D3PM00077J","DOIUrl":"https://doi.org/10.1039/D3PM00077J","url":null,"abstract":"<p >The application of nanotherapeutics is being considered as one of the most sought-after strategies to combat the threat posed by drug resistant bacteria. One promising type of nanotherapeutic is biogenic silver nanoparticles (bAgNPs) generated through exploiting the reducing potential of plant extracts. Herein, bAgNPs were synthesized at pH 7.4 (bAgNPs) and pH 10 (bAgNPs@pH) through green chemistry approaches using an extract of <em>Phyllanthus emblica</em> fruit as a source of reducing agent. The physicochemical properties, antibacterial potential, and biocompatibility of the as-synthesized bAgNPs were determined. The average size of bAgNPs and bAgNPs@pH was 15.3 and 20.1 nm, respectively, and both types of nanoparticles were negatively charged (<em>i.e.</em>, ∼−25 mV). The as-synthesized bAgNPs exhibited excellent antibacterial activity against different bacterial strains such as <em>Bacillus subtilis</em> RBW, <em>Escherichia coli</em> DH5a, <em>Salmonella typhi</em>, <em>Hafnia alvei</em>, enteropathogenic <em>E. coli</em>, <em>Vibrio cholerae</em>, and <em>Staphylococcus aureus</em>. The most effective antibacterial activity of bAgNPs and bAgNPs@pH was observed against <em>Hafnia alvei</em>, a Gram-negative bacterium, with a zone of inhibition (ZOI) of ∼24 and 26 mm in diameter, respectively. The nanoparticles exhibited antibacterial activity through damaging the bacterial cell wall, oxidizing the membrane fatty acids, and interacting with cellular macromolecules to bring about bacterial death. Furthermore, bAgNPs showed excellent hemocompatibility against human red blood cells, and there was no significant toxicity observed in rat serum ALT, AST, γ-GT, and creatinine levels. Thus, bAgNPs synthesized using <em>Phyllanthus emblica</em> fruit extract hold great promise as nanotherapeutics to combat a broad spectrum of pathogenic bacteria. Future directions may involve further exploration of the potential applications of biogenic silver nanoparticles in clinical settings, including studies on long-term efficacy, extensive <em>in vivo</em> toxicity profiles, and scalable production methods for clinical use.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 245-258"},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/pm/d3pm00077j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}