Pub Date : 2024-04-01Epub Date: 2024-03-06DOI: 10.2217/nnm-2023-0266
Jun Li, Fei Xie, Xuemei Ma
Ischemic stroke, prevalent among the elderly, necessitates attention to reperfusion injury post treatment. Limited drug access to the brain, owing to the blood-brain barrier, restricts clinical applications. Identifying efficient drug carriers capable of penetrating this barrier is crucial. Blood-brain barrier transporters play a vital role in nutrient transport to the brain. Recently, nanoparticles emerged as drug carriers, enhancing drug permeability via surface-modified ligands. This article introduces the blood-brain barrier structure, elucidates reperfusion injury pathogenesis, compiles ischemic stroke treatment drugs, explores nanomaterials for drug encapsulation and emphasizes their advantages over conventional drugs. Utilizing nanoparticles as drug-delivery systems offers targeting and efficiency benefits absent in traditional drugs. The prospects for nanomedicine in stroke treatment are promising.
{"title":"Advances in nanomedicines: a promising therapeutic strategy for ischemic cerebral stroke treatment.","authors":"Jun Li, Fei Xie, Xuemei Ma","doi":"10.2217/nnm-2023-0266","DOIUrl":"10.2217/nnm-2023-0266","url":null,"abstract":"<p><p>Ischemic stroke, prevalent among the elderly, necessitates attention to reperfusion injury post treatment. Limited drug access to the brain, owing to the blood-brain barrier, restricts clinical applications. Identifying efficient drug carriers capable of penetrating this barrier is crucial. Blood-brain barrier transporters play a vital role in nutrient transport to the brain. Recently, nanoparticles emerged as drug carriers, enhancing drug permeability via surface-modified ligands. This article introduces the blood-brain barrier structure, elucidates reperfusion injury pathogenesis, compiles ischemic stroke treatment drugs, explores nanomaterials for drug encapsulation and emphasizes their advantages over conventional drugs. Utilizing nanoparticles as drug-delivery systems offers targeting and efficiency benefits absent in traditional drugs. The prospects for nanomedicine in stroke treatment are promising.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"811-835"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2024-02-02DOI: 10.2217/nnm-2023-0314
Geng Lu, Chuangzan Yang, Kedi Chu, Yi Zhu, Sa Huang, Juying Zheng, Huanhuan Jia, Xiaofang Li, Junfeng Ban
Background: Osteoarthritis causes tremendous damage to the joints, reducing the quality of life and imposing significant financial burden. An implantable drug-delivery system can improve the symptomatic manifestations with low doses and frequencies. However, the free drug has short retention in the joint cavity. Materials & methods: This study used electrostatic spinning technology to create an implantable drug-delivery system loaded with celecoxib (celecoxib nanofibers [Cel-NFs]) to improve retention and bioavailability. Results: Cel-NFs exhibited good formability, hydrophilicity and tensile properties. Cel-NFs were able to continuously release drugs for 2 weeks and increase the uptake capacity of Raw 264.7 cells, ultimately ameliorating symptoms in osteoarthritis rats. Conclusion: These results suggest that Cel-NFs can effectively ameliorate cartilage damage, reduce joint pain and alleviate osteoarthritis progression.
背景:骨关节炎会对关节造成巨大损害,降低生活质量,并带来沉重的经济负担。植入式给药系统能以低剂量和低频率改善症状表现。然而,游离药物在关节腔内的存留时间较短。材料与方法:本研究利用静电纺丝技术创建了一种植入式给药系统,其中装载了塞来昔布(塞来昔布纳米纤维 [Cel-NFs]),以提高药物的保留率和生物利用度。研究结果塞来昔布纳米纤维具有良好的成型性、亲水性和拉伸性。Cel-NFs 能够持续释放药物 2 周,并能提高 Raw 264.7 细胞的吸收能力,最终改善骨关节炎大鼠的症状。结论这些结果表明,Cel-NFs 能有效改善软骨损伤、减轻关节疼痛并缓解骨关节炎的进展。
{"title":"Implantable celecoxib nanofibers made by electrospinning: fabrication and characterization.","authors":"Geng Lu, Chuangzan Yang, Kedi Chu, Yi Zhu, Sa Huang, Juying Zheng, Huanhuan Jia, Xiaofang Li, Junfeng Ban","doi":"10.2217/nnm-2023-0314","DOIUrl":"10.2217/nnm-2023-0314","url":null,"abstract":"<p><p><b>Background:</b> Osteoarthritis causes tremendous damage to the joints, reducing the quality of life and imposing significant financial burden. An implantable drug-delivery system can improve the symptomatic manifestations with low doses and frequencies. However, the free drug has short retention in the joint cavity. <b>Materials & methods:</b> This study used electrostatic spinning technology to create an implantable drug-delivery system loaded with celecoxib (celecoxib nanofibers [Cel-NFs]) to improve retention and bioavailability. <b>Results:</b> Cel-NFs exhibited good formability, hydrophilicity and tensile properties. Cel-NFs were able to continuously release drugs for 2 weeks and increase the uptake capacity of Raw 264.7 cells, ultimately ameliorating symptoms in osteoarthritis rats. <b>Conclusion:</b> These results suggest that Cel-NFs can effectively ameliorate cartilage damage, reduce joint pain and alleviate osteoarthritis progression.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"657-669"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2024-03-01DOI: 10.2217/nnm-2023-0313
Ying Tan, Xun Wang, Yu Gu, Xue Bao, He Lu, Xuan Sun, Lina Kang, Biao Xu
Aim: This study aimed to develop biomimetic nanoparticles (NPs) of roflumilast (ROF) for attenuating myocardial ischemia/reperfusion (MI/R) injury. Materials & methods: We synthesized biomimetic ROF NPs and assembled ROF NPs in neutrophil and endothelial cell membranes (NE/ROF NPs). The physical properties of NE/ROF NPs were characterized and biological functions of NE/ROF NPs were tested in vitro. Targeting characteristics, therapeutic efficacy and safety of NE/ROF NPs were examined in mice model of MI/R. Results: NE/ROF NPs exhibited significant anti-inflammatory and antiadhesion effects. Meanwhile, they was effective in reducing MI/R injury in mice. Furthermore, NE/ROF NPs exhibited stronger targeting capabilities and demonstrated good safety. Conclusion: NE/ROF NPs may be a versatile biomimetic drug-delivery system for attenuating MI/R injury.
{"title":"Neutrophil and endothelial cell membranes coassembled roflumilast nanoparticles attenuate myocardial ischemia/reperfusion injury.","authors":"Ying Tan, Xun Wang, Yu Gu, Xue Bao, He Lu, Xuan Sun, Lina Kang, Biao Xu","doi":"10.2217/nnm-2023-0313","DOIUrl":"10.2217/nnm-2023-0313","url":null,"abstract":"<p><p><b>Aim:</b> This study aimed to develop biomimetic nanoparticles (NPs) of roflumilast (ROF) for attenuating myocardial ischemia/reperfusion (MI/R) injury. <b>Materials & methods:</b> We synthesized biomimetic ROF NPs and assembled ROF NPs in neutrophil and endothelial cell membranes (NE/ROF NPs). The physical properties of NE/ROF NPs were characterized and biological functions of NE/ROF NPs were tested <i>in vitro</i>. Targeting characteristics, therapeutic efficacy and safety of NE/ROF NPs were examined in mice model of MI/R. <b>Results:</b> NE/ROF NPs exhibited significant anti-inflammatory and antiadhesion effects. Meanwhile, they was effective in reducing MI/R injury in mice. Furthermore, NE/ROF NPs exhibited stronger targeting capabilities and demonstrated good safety. <b>Conclusion:</b> NE/ROF NPs may be a versatile biomimetic drug-delivery system for attenuating MI/R injury.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"779-797"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2024-02-22DOI: 10.2217/nnm-2023-0310
Federica Barbugian, Francesca Cadamuro, Francesco Nicotra, Claudia Riccardi, Laura Russo
Aim: Cell microenvironment contains a plethora of information that influences cell modulation. Indeed, the extracellular matrix plays a central role in tissue development. Reproducing the cell-extracellular matrix crosstalk able to recapitulate both physical and biochemical signals is crucial to obtain functional tissue models or regenerative strategies. Materials & methods: Here, a combined method is proposed to easily functionalize collagen surface films, tailoring morphological properties. Oxygen nonthermal plasma treatment and glyco-conjugation with chondroitin sulfate are used to modify surface properties. Results: It results in higher adhesion, proliferation and morphological organization of U87 glioblastoma cells. Conclusion: Our finding suggests new promising strategies for the development of collagen-based biomaterials, which can be employed for advanced in vitro models.
{"title":"Plasma-treated collagen functionalized with chondroitin sulfate as bioactive and nanostructured extracellular matrix mimics.","authors":"Federica Barbugian, Francesca Cadamuro, Francesco Nicotra, Claudia Riccardi, Laura Russo","doi":"10.2217/nnm-2023-0310","DOIUrl":"10.2217/nnm-2023-0310","url":null,"abstract":"<p><p><b>Aim:</b> Cell microenvironment contains a plethora of information that influences cell modulation. Indeed, the extracellular matrix plays a central role in tissue development. Reproducing the cell-extracellular matrix crosstalk able to recapitulate both physical and biochemical signals is crucial to obtain functional tissue models or regenerative strategies. <b>Materials & methods:</b> Here, a combined method is proposed to easily functionalize collagen surface films, tailoring morphological properties. Oxygen nonthermal plasma treatment and glyco-conjugation with chondroitin sulfate are used to modify surface properties. <b>Results:</b> It results in higher adhesion, proliferation and morphological organization of U87 glioblastoma cells. <b>Conclusion:</b> Our finding suggests new promising strategies for the development of collagen-based biomaterials, which can be employed for advanced <i>in vitro</i> models.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"799-810"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2024-03-06DOI: 10.2217/nnm-2023-0344
Abdolreza Esmaeilzadeh, Pegah Moharrami Yeganeh, Mahdis Nazari, Kimia Esmaeilzadeh
Chronic nonhealing wounds pose a serious challenge to regaining skin function and integrity. Platelet-derived extracellular vesicles (PEVs) are nanostructured particles with the potential to promote wound healing since they can enhance neovascularization and cell migration and reduce inflammation and scarring. This work provides an innovative overview of the technical laboratory issues in PEV production, PEVs' role in chronic wound healing and the benefits and challenges in its clinical translation. The article also explores the challenges of proper sourcing, extraction techniques and storage conditions, and discusses the necessity of further evaluations and combinational therapeutics, including dressing biomaterials, M2-derived exosomes, mesenchymal stem cells-derived extracellular vesicles and microneedle technology, to boost their therapeutic efficacy as advanced strategies for wound healing.
{"title":"Platelet-derived extracellular vesicles: a new-generation nanostructured tool for chronic wound healing.","authors":"Abdolreza Esmaeilzadeh, Pegah Moharrami Yeganeh, Mahdis Nazari, Kimia Esmaeilzadeh","doi":"10.2217/nnm-2023-0344","DOIUrl":"10.2217/nnm-2023-0344","url":null,"abstract":"<p><p>Chronic nonhealing wounds pose a serious challenge to regaining skin function and integrity. Platelet-derived extracellular vesicles (PEVs) are nanostructured particles with the potential to promote wound healing since they can enhance neovascularization and cell migration and reduce inflammation and scarring. This work provides an innovative overview of the technical laboratory issues in PEV production, PEVs' role in chronic wound healing and the benefits and challenges in its clinical translation. The article also explores the challenges of proper sourcing, extraction techniques and storage conditions, and discusses the necessity of further evaluations and combinational therapeutics, including dressing biomaterials, M2-derived exosomes, mesenchymal stem cells-derived extracellular vesicles and microneedle technology, to boost their therapeutic efficacy as advanced strategies for wound healing.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"915-941"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2024-03-26DOI: 10.2217/nnm-2023-0325
Karishma Niveria, Mohammad ZafarYab, Largee Biswas, Asiya Mahtab, Anita Kamra Verma
Aim: Osteoporosis is a systemic skeletal disorder characterized by reduced osteoblast differentiation, predominantly by overexpression of the Sost gene. A layer-by-layer approach enabled encapsulation of Sost siRNA to enhance the short half-life and poor transfection capacity of siRNA. Materials & methods: Polyethyleneimine and siRNA on chitosan-coated gold nanoparticles (PEI/siRNA/Cs-AuNPs) were engineered using chitosan-reduced gold nanoparticles. They were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared and gel-mobility assays. Detailed in vitro experiments, gene silencing and western blots were performed. Results: A total of 80% knockdown of the target sclerostin protein was observed by PEI/siRNA/Cs-AuNPs, q-PCR showed threefold downregulation of the Sost gene. Osteogenic markers RunX2 and Alp were significantly upregulated. Conclusion: We report a safe, biocompatible nanotherapeutic strategy to enhance siRNA protection and subsequent silencing to augment bone formation.
{"title":"Leveraging selective knockdown of <i>Sost</i> gene by polyethyleneimine-siRNA-chitosan reduced gold nanoparticles to promote osteogenesis in MC3T3-E1 & MEF cells.","authors":"Karishma Niveria, Mohammad ZafarYab, Largee Biswas, Asiya Mahtab, Anita Kamra Verma","doi":"10.2217/nnm-2023-0325","DOIUrl":"10.2217/nnm-2023-0325","url":null,"abstract":"<p><p><b>Aim:</b> Osteoporosis is a systemic skeletal disorder characterized by reduced osteoblast differentiation, predominantly by overexpression of the <i>Sost</i> gene. A layer-by-layer approach enabled encapsulation of <i>Sost</i> siRNA to enhance the short half-life and poor transfection capacity of siRNA. <b>Materials & methods:</b> Polyethyleneimine and siRNA on chitosan-coated gold nanoparticles (PEI/siRNA/Cs-AuNPs) were engineered using chitosan-reduced gold nanoparticles. They were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared and gel-mobility assays. Detailed <i>in vitro</i> experiments, gene silencing and western blots were performed. <b>Results:</b> A total of 80% knockdown of the target sclerostin protein was observed by PEI/siRNA/Cs-AuNPs, q-PCR showed threefold downregulation of the <i>Sost</i> gene. Osteogenic markers <i>RunX2</i> and <i>Alp</i> were significantly upregulated. <b>Conclusion:</b> We report a safe, biocompatible nanotherapeutic strategy to enhance siRNA protection and subsequent silencing to augment bone formation.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"895-914"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2024-03-04DOI: 10.2217/nnm-2023-0335
Qiong Yi, Shumin He, Kai Liao, Zongxiang Yue, Ling Mei
Aims: Preparation and evaluation of nanoparticles for tumor chemotherapy and immunotherapy mild photothermal therapy and oxaliplatin. Methods: The double emulsion method was used for nanoparticle preparations. Polydopamine was deposited on the surface, which was further modified with folic acid. Cytotoxicity assays were carried out by cell counting kit-8. In vivo antitumor assays were carried out on 4T1 tumor-bearing mice. Results: The nanoparticles exhibited a 190 nm-diameter pomegranate-like sphere, which could increase temperature to 43-46°C. In vivo distribution showed enhanced accumulation. The nanoparticles generated stronger immunogenic cell death effects. By stimulating the maturation of dendritic cells, mild photothermal therapy combined with oxaliplatin significantly increased the antitumor effect by a direct killing effect and activation of immunotherapy. Conclusion: This study provided a promising strategy of combination therapy for tumors.
{"title":"Nanoparticles integrated with mild photothermal therapy and oxaliplatin for tumor chemotherapy and immunotherapy.","authors":"Qiong Yi, Shumin He, Kai Liao, Zongxiang Yue, Ling Mei","doi":"10.2217/nnm-2023-0335","DOIUrl":"10.2217/nnm-2023-0335","url":null,"abstract":"<p><p><b>Aims:</b> Preparation and evaluation of nanoparticles for tumor chemotherapy and immunotherapy mild photothermal therapy and oxaliplatin. <b>Methods:</b> The double emulsion method was used for nanoparticle preparations. Polydopamine was deposited on the surface, which was further modified with folic acid. Cytotoxicity assays were carried out by cell counting kit-8. <i>In vivo</i> antitumor assays were carried out on 4T1 tumor-bearing mice. <b>Results:</b> The nanoparticles exhibited a 190 nm-diameter pomegranate-like sphere, which could increase temperature to 43-46°C. <i>In vivo</i> distribution showed enhanced accumulation. The nanoparticles generated stronger immunogenic cell death effects. By stimulating the maturation of dendritic cells, mild photothermal therapy combined with oxaliplatin significantly increased the antitumor effect by a direct killing effect and activation of immunotherapy. <b>Conclusion:</b> This study provided a promising strategy of combination therapy for tumors.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"841-854"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aims: This study was aimed to formulate erlotinib (ERL)-loaded transferosomal gel (ERL@TG) intended for topical application for the treatment of ductal carcinoma in situ. Materials & methods: The optimized process involved a thin-film hydration method to generate ERL-loaded transferosomes (ERL@TFS), which was incorporated into a carbopol gel matrix to generate ERL@TG. The optimized formulation was characterized in vitro followed by cytotoxicity evaluation on MCF-7 breast cancer cell lines and acute toxicity and skin irritation studies was performed in vivo. Results: In a comparative assessment against plain ERL, ERL@TG displayed enhanced efficacy against MCF-7 cell lines, reflected in considerably lower IC50 values with an enhanced safety profile. Conclusion: Optimized ERL@TG was identified as a promising avenue for addressing ductal carcinoma in situ breast cancer.
{"title":"Development of erlotinib-loaded nanotransferosomal gel for the topical treatment of ductal carcinoma <i>in situ</i>.","authors":"Bharti Mangla, Priya Mittal, Pankaj Kumar, Shamama Javed, Waquar Ahsan, Geeta Aggarwal","doi":"10.2217/nnm-2023-0260","DOIUrl":"10.2217/nnm-2023-0260","url":null,"abstract":"<p><p><b>Aims:</b> This study was aimed to formulate erlotinib (ERL)-loaded transferosomal gel (ERL@TG) intended for topical application for the treatment of ductal carcinoma <i>in situ</i>. <b>Materials & methods:</b> The optimized process involved a thin-film hydration method to generate ERL-loaded transferosomes (ERL@TFS), which was incorporated into a carbopol gel matrix to generate ERL@TG. The optimized formulation was characterized <i>in vitro</i> followed by cytotoxicity evaluation on MCF-7 breast cancer cell lines and acute toxicity and skin irritation studies was performed <i>in vivo</i>. <b>Results:</b> In a comparative assessment against plain ERL, ERL@TG displayed enhanced efficacy against MCF-7 cell lines, reflected in considerably lower IC<sub>50</sub> values with an enhanced safety profile. <b>Conclusion:</b> Optimized ERL@TG was identified as a promising avenue for addressing ductal carcinoma <i>in situ</i> breast cancer.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"855-874"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}