Expert Opinion on Drug Delivery最新文献

{"title":"Biomedical applications of PLGA nanoparticles in nanomedicine: advances in drug delivery systems and cancer therapy.","authors":"Asghar Narmani,&nbsp;Roghayyeh Jahedi,&nbsp;Ehsan Bakhshian-Dehkordi,&nbsp;Saeid Ganji,&nbsp;Mahnaz Nemati,&nbsp;Ruhollah Ghahramani-Asl,&nbsp;Kave Moloudi,&nbsp;Seyed Mohammad Hosseini,&nbsp;Hamed Bagheri,&nbsp;Prashant Kesharwani,&nbsp;Ali Khani,&nbsp;Bagher Farhood,&nbsp;Amirhossein Sahebkar","doi":"10.1080/17425247.2023.2223941","DOIUrl":"10.1080/17425247.2023.2223941","url":null,"abstract":"<p><strong>Introduction: </strong>During the last decades, the ever-increasing proportion of patients with cancer has been led to serious concerns worldwide. Therefore, the development and use of novel pharmaceuticals, like nanoparticles (NPs)-based drug delivery systems (DDSs), can be potentially effective in cancer therapy.</p><p><strong>Area covered: </strong>Poly lactic-co-glycolic acid (PLGA) NPs, as a kind of bioavailable, biocompatible, and biodegradable polymers, have approved by the Food and Drug Administration (FDA) for some biomedical and pharmaceutical applications. PLGA is comprised of lactic acid (LA) and glycolic acid (GA) and their ratio could be controlled during various syntheses and preparation approaches. LA/GA ratio determines the stability and degradation time of PLGA; lower content of GA results in fast degradation. There are several approaches for preparing PLGA NPs that can affect their various aspects, such as size, solubility, stability, drug loading, pharmacokinetics, and pharmacodynamics, and so on.</p><p><strong>Expert opinion: </strong>These NPs have indicated the controlled and sustained drug release in the cancer site and can use in passive and active (via surface modification) DDSs. This review aims to provide an overview of PLGA NPs, their preparation approach and physicochemical aspects, drug release mechanism and the cellular fate, DDSs for efficient cancer therapy, and status in the pharmaceutical industry and nanomedicine.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":"20 7","pages":"937-954"},"PeriodicalIF":6.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10385614","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":"Utilization of endogenous albumin trafficking pathways in the lungs has potential to modestly increase the lung interstitial access and absorption of drug delivery systems after inhaled administration.","authors":"Jibriil P Ibrahim,&nbsp;Neville J Butcher,&nbsp;Ashok Kothapalli,&nbsp;Christopher N Subasic,&nbsp;Joanne T Blanchfield,&nbsp;Andrew K Whittaker,&nbsp;Michael R Whittaker,&nbsp;Lisa M Kaminskas","doi":"10.1080/17425247.2023.2244881","DOIUrl":"10.1080/17425247.2023.2244881","url":null,"abstract":"<p><strong>Objectives: </strong>Drug delivery systems typically show limited access to the lung interstitium and absorption after pulmonary delivery. The aim of this work was to undertake a proof-of-concept investigation into the potential of employing endogenous albumin and albumin absorption mechanisms in the lungs to improve lung interstitial access and absorption of inhaled drug delivery systems that bind albumin.</p><p><strong>Methods: </strong>The permeability of human albumin (HSA) through monolayers of primary human alveolar epithelia, small airway epithelia, and microvascular endothelium were investigated. The pulmonary pharmacokinetics of bovine serum albumin (BSA) was also investigated in efferent caudal mediastinal lymph duct-cannulated sheep after inhaled aerosol administration.</p><p><strong>Results: </strong>Membrane permeability coefficient values (P_app) of HSA increased in the order alveolar epithelia<small airway epithelia<microvascular endothelium, where the permeability of HSA through small airway and microvascular endothelia were approximately 4- and 28-fold higher than alveolar epithelia, respectively. Only 6.5% of the delivered BSA aerosol dose was absorbed from the lungs of sheep over 5 days, although half of the absorbed dose was absorbed via the lung lymph.</p><p><strong>Conclusion: </strong>Drug delivery systems that bind endogenous albumin may show a modest increase in lung permeability and absorption after inhaled delivery compared to systems that do not efficiently bind albumin.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":" ","pages":"1145-1155"},"PeriodicalIF":6.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9942337","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":"Synthetic engineered bacteria for cancer therapy.","authors":"Tong Gong,&nbsp;Jinhui Wu","doi":"10.1080/17425247.2023.2241367","DOIUrl":"10.1080/17425247.2023.2241367","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer mortality worldwide highlights the urgency for advanced therapeutic methods to fill the gaps in conventional cancer therapies. Bacteriotherapy is showing great potential in tumor regression due to the motility and colonization tendencies of bacteria. However, the complicated in vivo environment and tumor pathogenesis hamper the therapeutic outcomes. Synthetic engineering methods endow bacteria with flexible abilities both at the extracellular and intracellular levels to meet treatment requirements. In this review, we introduce synthetic engineering methods for bacterial modifications. We highlight the recent progress in engineered bacteria and explore how these synthetic methods endow bacteria with superior abilities in cancer therapy. The current clinical translations are further discussed. Overall, this review may shed light on the advancement of engineered bacteria for cancer therapy.</p><p><strong>Areas covered: </strong>Recent progress in synthetic methods for bacterial engineering and specific examples of their applications in cancer therapy are discussed in this review.</p><p><strong>Expert opinion: </strong>Bacteriotherapy bridges the gaps of conventional cancer therapies through the natural motility and colonization tendency of bacteria, as well as their synthetic engineering. Nevertheless, to fulfill the bacteriotherapy potential and move into clinical trials, more research focusing on its safety concerns should be conducted.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":"20 7","pages":"993-1013"},"PeriodicalIF":6.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10002428","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":"Sustained release ocular drug delivery systems for glaucoma therapy.","authors":"Zinah K Al-Qaysi,&nbsp;Ian G Beadham,&nbsp;Sianne L Schwikkard,&nbsp;Joseph C Bear,&nbsp;Ali A Al-Kinani,&nbsp;Raid G Alany","doi":"10.1080/17425247.2023.2219053","DOIUrl":"10.1080/17425247.2023.2219053","url":null,"abstract":"<p><strong>Introduction: </strong>Glaucoma is a group of progressive optic neuropathies resulting in irreversible blindness. It is associated with an elevation of intraocular pressure (>21 mm Hg) and optic nerve damage. Reduction of the intraocular pressure (IOP) through the administration of ocular hypotensive eye drops is one of the most common therapeutic strategies. Patient adherence to conventional eye drops remains a major obstacle in preventing glaucoma progression. Additional problems emerge from inadequate patient education as well as local and systemic side effects associated with adminstering ocular hypotensive drugs.</p><p><strong>Areas covered: </strong>Sustained-release drug delivery systems for glaucoma treatment are classified into extraocular systems including wearable ocular surface devices or multi-use (immediate-release) eye formulations (such as aqueous solutions, gels; ocular inserts, contact lenses, periocular rings, or punctual plugs) and intraocular drug delivery systems (such as intraocular implants, and microspheres for supraciliary drug delivery).</p><p><strong>Expert opinion: </strong>Sustained release platforms for the delivery of ocular hypotensive drugs (small molecules and biologics) may improve patient adherence and prevent vision loss. Such innovations will only be widely adopted when efficacy and safety has been established through large-scale trials. Sustained release drug delivery can improve glaucoma treatment adherence and reverse/prevent vision deterioration. It is expected that these approaches will improve clinical management and prognosis of glaucoma.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":"20 7","pages":"905-919"},"PeriodicalIF":6.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10007644","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":"Factors affecting the preparation of nanocrystals: characterization, surface modifications and toxicity aspects.","authors":"Shirleen Miriam Marques, Lalit Kumar","doi":"10.1080/17425247.2023.2218084","DOIUrl":"10.1080/17425247.2023.2218084","url":null,"abstract":"<p><strong>Introduction: </strong>The fabrication of well-defined nanocrystals in size and form is the focus of much investigation. In this work, we have critically reviewed several recent instances from the literature that shows how the production procedure affects the physicochemical properties of the nanocrystals.</p><p><strong>Areas covered: </strong>Scopus, MedLine, PubMed, Web of Science, and Google Scholar were searched for peer-review articles published in the past few years using different key words. Authors chose relevant publications from their files for this review. This review focuses on the range of techniques available for producing nanocrystals. We draw attention to several recent instances demonstrating the impact of various process and formulation variables that affect the nanocrystals' physicochemical properties. Moreover, various developments in the characterization techniques explored for nanocrystals concerning their size, morphology, etc. have been discussed. Last but not least, recent applications, the effect of surface modifications, and the toxicological traits of nanocrystals have also been reviewed.</p><p><strong>Expert opinion: </strong>The selection of an appropriate production method for the formation of nanocrystals, together with a deep understanding of the relationship between the drug's physicochemical properties, unique features of the various formulation alternatives, and anticipated in-vivo performance, would significantly reduce the risk of failure during human clinical trials that are inadequate.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":"20 7","pages":"871-894"},"PeriodicalIF":6.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10009552","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":"Strategies for overcoming the biological barriers associated with the administration of inhaled monoclonal antibodies for lung diseases.","authors":"Maria Gabriella Matera,&nbsp;Luigino Calzetta,&nbsp;Barbara Rinaldi,&nbsp;Mario Cazzola,&nbsp;Paola Rogliani","doi":"10.1080/17425247.2023.2260310","DOIUrl":"10.1080/17425247.2023.2260310","url":null,"abstract":"<p><strong>Introduction: </strong>Monoclonal antibodies (mAbs) should be administered by inhalation rather than parenterally to improve their efficiency in lung diseases. However, the pulmonary administration of mAbs in terms of aerosol technology and the formulation for inhalation is difficult.</p><p><strong>Areas covered: </strong>The feasible or suitable strategies for overcoming the barriers associated with administering mAbs are described.</p><p><strong>Expert opinion: </strong>Providing mAbs via inhalation to individuals with lung disorders is still difficult. However, inhalation is a desirable method for mAb delivery. Inhaled mAb production needs to be well thought out. The illness, the patient group(s), the therapeutic molecule selected, its interaction with the biological barriers in the lungs, the formulation, excipients, and administration systems must all be thoroughly investigated. Therefore, to create inhaled mAbs that are stable and efficacious, it will be essential to thoroughly examine the problems linked to instability and protein aggregation. More excipients will also need to be manufactured, expanding the range of formulation design choices. Another crucial requirement is for novel carriers for topical delivery to the lungs since carriers might significantly enhance proteins' stability and pharmacokinetic profile.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":" ","pages":"1085-1095"},"PeriodicalIF":6.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10670945","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":"Advances in soft mist inhalers.","authors":"Varsha Komalla,&nbsp;Chun Yuen Jerry Wong,&nbsp;Imco Sibum,&nbsp;Bernhard Muellinger,&nbsp;Wietze Nijdam,&nbsp;Vishal Chaugule,&nbsp;Julio Soria,&nbsp;Hui Xin Ong,&nbsp;Nicolas A Buchmann,&nbsp;D Traini","doi":"10.1080/17425247.2023.2231850","DOIUrl":"10.1080/17425247.2023.2231850","url":null,"abstract":"<p><strong>Introduction: </strong>Soft mist inhalers (SMIs) are propellant-free inhalers that utilize mechanical power to deliver single or multiple doses of inhalable drug aerosols in the form of a slow mist to patients. Compared to traditional inhalers, SMIs allow for a longer and slower release of aerosol with a smaller ballistic effect, leading to a limited loss in the oropharyngeal area, whilst requiring little coordination of actuation and inhalation by patients. Currently, the Respimat® is the only commercially available SMI, with several others in different stages of preclinical and clinical development.</p><p><strong>Areas covered: </strong>The primary purpose of this review is to critically assess recent advances in SMIs for the delivery of inhaled therapeutics.</p><p><strong>Expert opinion: </strong>Advanced particle formulations, such as nanoparticles which target specific areas of the lung, Biologics, such as vaccines, proteins, and antibodies (which are sensitive to aerosolization), are expected to be generally delivered by SMIs. Furthermore, repurposed drugs are expected to constitute a large share of future formulations to be delivered by SMIs. SMIs can also be employed for the delivery of formulations that target systemic diseases. Finally, digitalizing SMIs would improve patient adherence and provide clinicians with fundamental insights into patients' treatment progress.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":" ","pages":"1055-1070"},"PeriodicalIF":6.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9764523","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":"The impact of common pharmaceutical excipients on the gut microbiota.","authors":"Santhni Subramaniam,&nbsp;Srinivas Kamath,&nbsp;Amin Ariaee,&nbsp;Clive Prestidge,&nbsp;Paul Joyce","doi":"10.1080/17425247.2023.2223937","DOIUrl":"10.1080/17425247.2023.2223937","url":null,"abstract":"<p><strong>Introduction: </strong>Increasing attention is being afforded to understanding the bidirectional relationships that exist between oral medications and the gut microbiota, in an attempt to optimize pharmacokinetic performance and mitigate unwanted side effects. While a wealth of research has investigated the direct impact of active pharmaceutical ingredients (APIs) on the gut microbiota, the interactions between inactive pharmaceutical ingredients (i.e. excipients) and the gut microbiota are commonly overlooked, despite excipients typically representing over 90% of the final dosage form.</p><p><strong>Areas covered: </strong>Known excipient-gut microbiota interactions for various classes of inactive pharmaceutical ingredients, including solubilizing agents, binders, fillers, sweeteners, and color additives, are reviewed in detail.</p><p><strong>Expert opinion: </strong>Clear evidence indicates that orally administered pharmaceutical excipients directly interact with gut microbes and can either positively or negatively impact gut microbiota diversity and composition. However, these relationships and mechanisms are commonly overlooked during drug formulation, despite the potential for excipient-microbiota interactions to alter drug pharmacokinetics and interfere with host metabolic health. The insights derived from this review will inform pharmaceutical scientists with the necessary design considerations for mitigating potential adverse pharmacomicrobiomic interactions when formulating oral dosage forms, ultimately providing clear avenues for improving therapeutic safety and efficacy.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":" ","pages":"1297-1314"},"PeriodicalIF":6.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9707861","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":"GPP-TSAIII nanocomposite hydrogel-based photothermal ablation facilitates melanoma therapy.","authors":"Xing Huang,&nbsp;Yihao He,&nbsp;Miao Zhang,&nbsp;Zhenhui Lu,&nbsp;Tong Zhang,&nbsp;Bing Wang","doi":"10.1080/17425247.2023.2200997","DOIUrl":"10.1080/17425247.2023.2200997","url":null,"abstract":"<p><strong>Background: </strong>Photothermal therapy (PTT) is a promising cancer treatment, but its application is limited by low photoconversion efficiency. In this study, we aimed to develop a novel graphene oxide (GO)-based nanocomposite hydrogel to improve the bioavailability of timosaponin AIII (TSAIII) while maximizing PTT efficacy and enhancing the antitumor effect.</p><p><strong>Methods: </strong>GO was modified via physical cross-linking with polyvinyl alcohol. The pore structure of the gel was adjusted by repeated freeze-thawing and the addition of polyethylene glycol 2000 to obtain a nanocomposite hydrogel (GPP). The GPP loaded with TSAIII constituted a GPP-TSAIII drug delivery system, and its efficacy was evaluated by in vitro cytotoxicity, apoptosis, migration, and uptake analyses, and in vivo antitumor studies.</p><p><strong>Results: </strong>The encapsulation rate of GPP-TSAIII was 66.36 ± 3.97%, with slower in vitro release and higher tumor cell uptake (6.4-fold) compared to TSAIII. GPP-TSAIII in combination with PTT showed better bioavailability and antitumor effects in vivo than did TSAIII, with a 1.9-fold higher tumor suppression rate than the TSAIII group.</p><p><strong>Conclusions: </strong>GPP is a potential vehicle for delivery of TSAIII-like poor water-soluble anticancer drugs. The innovative PTT co-delivery system may serve as a safe and effective melanoma treatment platform for further anticancer translational purposes.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":" ","pages":"1277-1295"},"PeriodicalIF":6.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977525","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":"The importance of dissolution for orally inhaled drug products: pharmaceutical, regulatory, and clinical considerations.","authors":"Karin Somby,&nbsp;Martin Hingle,&nbsp;Ivana Tomic,&nbsp;Ben Forbes","doi":"10.1080/17425247.2023.2205636","DOIUrl":"10.1080/17425247.2023.2205636","url":null,"abstract":"Almost all current orally inhaled drug products (OIDPs) are for the treatment of respiratory diseases, and many have been designed using molecular or formulation strategies to retain drug in the lungs. After deposition in the lungs, the rate at which aerosol particles release drug into the lung lining fluid is a determinant of local bioavailability for drugs with poor solubility. Slow dissolution provides an absorption rate-limiting mechanism for prolonging lung exposure to an inhaled drug and extending the duration of pharmacodynamic effects. Historically, the Inhalation Ad Hoc Advisory Panel of the United States (US) Pharmacopoeia (2008) considered that there was an absence of ‘compelling evidence that dissolution testing is kinetically important for currently approved inhaled drug products’; a conclusion supported in 2012 by an IPAC-RS Dissolution Working Group [1]. Paradoxically, there has since been an intensification of interest in dissolution testing for OIDPs, driven at least in part by the US Food and Drug Administration sponsorship of research in this area [2,3]. More recently, solubility has been proposed as a key attribute of the drug substance and dissolution as a key attribute of the drug product under the foundational principles of an inhaled biopharmaceuticals classification system (iBCS) [4]. This brings closer the prospect of dissolution being recognized formally as a critical quality attribute for certain classes of OIDP and that in vitro dissolution methods will be required to characterize OIDPs in a way that is biorelevant, predictive, and can be used with confidence by medicine developers and regulators. Developing a biorelevant dissolution assay for OIDPs is challenging in practice, requiring collection of a relevant aerosol fraction, a dissolution apparatus, and dissolution medium that replicate the key determinants of dissolution in the lungs and methods for data analysis and interpretation. This article summarizes briefly recent developments in dissolution testing with a focus on pharmaceutical, regulatory, and clinical relevance (Figure 1).","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":" ","pages":"1033-1036"},"PeriodicalIF":6.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9384892","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}