Drug Delivery and Translational Research最新文献

{"title":"Harnessing curcumin in a multifunctional biodegradable metal-organic framework (bio-MOF) for targeted colorectal cancer theranostics.","authors":"Maryam Babaei, Amir Abrishami, Sonia Iranpour, Amir Sh Saljooghi, Maryam M Matin","doi":"10.1007/s13346-024-01707-6","DOIUrl":"10.1007/s13346-024-01707-6","url":null,"abstract":"<p><p>Despite significant advancements in managing colorectal cancer (CRC), the issues of efficient diagnosis and targeted therapy remain demanding. To address these challenges and improve treatment outcomes while reducing the cost and side effects, there is a need for more effective theranostic systems that combine diagnostic techniques with therapeutic modalities. This study introduces a pioneering approach for the synthesis of a porous bio-MOF (biodegradable metal-organic framework) using iron as the metal component and curcumin as the pharmaceutical ingredient. Subsequently, the developed drug delivery system was equipped with the anticancer drug doxorubicin (DOX), coated with biocompatible polyethylene glycol (PEG), and targeted with a CRC-specific aptamer (EpCAM). The physicochemical characterization confirmed the successful synthesis of the bio-MOF, demonstrating high encapsulation efficiency and pH-dependent release of DOX. In vitro studies for anticancer activity, cellular uptake, and mechanism of cell death demonstrated that in the case of positive EpCAM HT-29 cells, Apt-PEG-MOF@DOX had enhanced internalization that resulted in massive apoptosis. In vivo studies of the nanoparticles were then conducted in immunocompromised C57BL/6 mice bearing HT-29 tumors. These studies showed that the targeted platform could induce efficient tumor regression with reduced systemic toxicity. The targeted bio-MOF also exhibited MRI imaging properties useful for monitoring tumors. Significantly, the biocompatibility of the introduced bio-MOF was enhanced by pursuing the green synthesis method, which does not engage toxic solvents and strong acids. Overall, this multimodal system acts diversely as a tumor imaging agent and a therapeutic delivery platform suitable for CRC theranostics.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1719-1738"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticles in the battle against Candida auris biofilms: current advances and future prospects.","authors":"Bahgat Fayed","doi":"10.1007/s13346-024-01749-w","DOIUrl":"10.1007/s13346-024-01749-w","url":null,"abstract":"<p><p>Candida auris has emerged as a significant global health threat due to its multidrug resistance and ability to form robust biofilms, particularly on medical devices and hospital surfaces. Biofilms protect C. auris from antifungal treatments and the host immune response, making infections persistent and difficult to control. This review explores the potential of nanoparticles to overcome the limitations of traditional antifungal therapies in combating C. auris biofilms. Nanoparticles, with their unique physicochemical properties, offer promising strategies to penetrate biofilm matrices, deliver antifungal agents, and disrupt biofilm structure. Various types of nanoparticles, including metallic, polymeric, lipid-based, and cyclodextrin-based, demonstrate enhanced biofilm penetration and antifungal activity. Their ability to generate reactive oxygen species, disrupt cell adhesion, and release antifungals in a controlled manner makes them ideal candidates for biofilm-targeted therapies. This review presents the current advancements in nanoparticle-based solutions, emphasizing the need for further research into their mechanisms of action, safety, and clinical application. By addressing the challenge of C. auris biofilms specifically, this review provides a critical synthesis of existing knowledge and identifies future directions for developing effective antifungal therapies using nanotechnology.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1496-1512"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral delivery of stabilized lipid nanoparticles for nucleic acid therapeutics.","authors":"Kanika Suri, Liam Pfeifer, Donna Cvet, Angela Li, Michael McCoy, Amit Singh, Mansoor M Amiji","doi":"10.1007/s13346-024-01709-4","DOIUrl":"10.1007/s13346-024-01709-4","url":null,"abstract":"<p><p>Gastrointestinal disorders originate in the gastrointestinal tract (GIT), and the therapies can benefit from direct access to the GIT achievable through the oral route. RNA molecules show great promise therapeutically but are highly susceptible to degradation and often require a carrier for cytoplasmic access. Lipid nanoparticles (LNPs) are clinically proven drug-delivery agents, primarily administered parenterally. An ideal Orally Delivered (OrD) LNP formulation should overcome the diverse GI environment, successfully delivering the drug to the site of action. A versatile OrD LNP formulation has been developed to encapsulate and deliver siRNA and mRNA in this paper. The formulations were prepared by the systematic addition of cationic lipid to the base LNP formulation, keeping the total of cationic lipid and ionizable lipid to 50 mol%. Biorelevant media stability depicted increased resistance to bile salt mediated destabilization upon the addition of the cationic lipid, however the in vitro efficacy data underscored the importance of the ionizable lipid. Based on this, OrD LNP was selected comprising of 20% cationic lipid and 30% ionizable lipid. Further investigation revealed the enhanced efficacy of OrD LNP in vitro after incubation in different dilutions of fasted gastric, fasted intestinal media, and mucin. Confocal imaging and flow cytometry confirmed uptake while in vivo studies demonstrated efficacy with siRNA and mRNA as payloads. Taken together, this research introduces OrD LNP to deliver nucleic acid locally to the GIT.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1755-1769"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo evaluation of in situ forming polyester implants for the extended release of carvedilol.","authors":"Samer R Abulateefeh, Raghad M Abuhamdan, Husam Saed, Mohammad Alsalem, Khaldoun Shnewer","doi":"10.1007/s13346-024-01706-7","DOIUrl":"10.1007/s13346-024-01706-7","url":null,"abstract":"<p><p>Polyester based in situ forming implants (ISFIs) are injectable long-acting drug delivery systems that offer a wide range of unique advantages. As a result of these advantages, two relatively high molecular weight, ester terminated grades of poly (D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide) (PLA) were evaluated for their ability (i) to form ISFIs loaded with carvedilol, and (ii) to control its release both in vitro and in vivo. At a polymeric concentration of 40% w/w, implant solutions were syringeable, injectable, and able to encapsulate carvedilol to a high degree (encapsulated drug% > 97%). When visualized using scanning electron microscopy (SEM), implants were found to have a dense thin surface atop porous sublayers. As for their in vitro evaluation, PLGA and PLA implants were able to maintain drug release over the course of 49 and 84 days, respectively. On the other hand, in vivo drug release from both implants was almost identical and lasted for only 42 days. This may be due to the overriding effect of the similar host environment at the injection site that diminished the effect of polymeric physiochemistry on phase inversion and drug release. Lastly, while the polymer-free drug/NMP solution completely released its drug content within the initial half hour in vitro, the formulation extended drug release in vivo. This could be due to a yet to be investigated interaction between carvedilol and NMP under in vivo conditions. These results cement the significance of formulating carvedilol loaded ISFIs for the management of chronic conditions.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1707-1718"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microneedle patch capable of dual drug release for drug delivery to brain tumors.","authors":"Robab Mousavi, Madjid Soltani, Mohammad Souri","doi":"10.1007/s13346-024-01696-6","DOIUrl":"10.1007/s13346-024-01696-6","url":null,"abstract":"<p><p>Primary brain tumors are mostly managed using surgical resection procedures. Nevertheless, in certain cases, a thin layer of tumors may remain outside of the resection process due to the possibility of permanent injury; these residual tumors expose patients to the risk of tumor recurrence. This study has introduced the use of microneedle patches implanted after surgery with a dual-release mechanism for the administration of doxorubicin. The proposed patches possess the capability to administer drugs directly to the residual tumors and initiate chemotherapy immediately following surgical procedures. Three-dimensional simulation of drug delivery to residual tumors in the brain has been performed based on a finite element method. The impact of four important parameters on drug delivery has been investigated, involving the fraction of drug released in the burst phase, the density of microneedles on the patch, the length of microneedles, and the microvascular density of the tumor. The simulation findings indicate that lowering the fraction of drug released in the initial burst phase reduces the maximum average concentration, but the sustained release that continues for a longer period, increasing the bioavailability of free drug. However, the area under curve (AUC) for different release rates remains unchanged due to the fact that an identical dose of drug is supplied in each instance. By increasing the density of microneedles on the patch, concentration accumulation is provided over an extensive region of tumor, which in turn induces more cancer cell death. A comparative analysis of various lengths reveals that longer microneedles facilitate profound penetration into the tumor layers and present better therapeutic response due to extensive area of the tumor which is exposure to chemotherapeutic drugs. Furthermore, high microvascular density, as a characteristic of the tumor microenvironment, is shown to have a significant impact on the blood microvessels drainage of drugs and consequently lower therapeutic response outcome. Our approach offers a computational framework for creating localized drug delivery systems and addressing the challenges related to residual brain tumors.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1567-1594"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the efficacy of Rose Bengal-PVA combinations within PCL/PLA implants for sustained cancer treatment.","authors":"Sara Demartis, Camila J Picco, Eneko Larrañeta, Anna Korelidou, Rayhanul Islam, Jonathan A Coulter, Paolo Giunchedi, Ryan F Donnelly, Giovanna Rassu, Elisabetta Gavini","doi":"10.1007/s13346-024-01711-w","DOIUrl":"10.1007/s13346-024-01711-w","url":null,"abstract":"<p><p>The current investigation aims to address the limitations of conventional cancer therapy by developing an advanced, long-term drug delivery system using biocompatible Rose Bengal (RB)-loaded polyvinyl alcohol (PVA) matrices incorporated into 3D printed polycaprolactone (PCL) and polylactic acid (PLA) implants. The anticancer drug RB's high solubility and low lipophilicity require frequent and painful administration to the tumour site, limiting its clinical application. In this study, RB was encapsulated in a PVA (RB@PVA) matrix to overcome these challenges and achieve a localised and sustained drug release system within a biodegradable implant designed to be implanted near the tumour site. The RB@PVA matrix demonstrated an RB loading efficiency of 77.34 ± 1.53%, with complete RB release within 30 min. However, when integrated into implants, the system provided a sustained RB release of 75.84 ± 8.75% over 90 days. Cytotoxicity assays on PC-3 prostate cancer cells indicated an IC50 value of 1.19 µM for RB@PVA compared to 2.49 µM for free RB, effectively inhibiting cancer cell proliferation. This innovative drug delivery system, which incorporates a polymer matrix within an implantable device, represents a significant advancement in the sustained release of hydrosoluble drugs. It holds promise for reducing the frequency of drug administration, thereby improving patient compliance and translating experimental research into practical therapeutic applications.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1770-1785"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication of 3D printed mutable drug delivery devices: a comparative study of volumetric and digital light processing printing.","authors":"Ye Chan Oh, Jun Jie Ong, Haya Alfassam, Eduardo Díaz-Torres, Alvaro Goyanes, Gareth R Williams, Abdul W Basit","doi":"10.1007/s13346-024-01697-5","DOIUrl":"10.1007/s13346-024-01697-5","url":null,"abstract":"<p><p>Mutable devices and dosage forms have the capacity to dynamically transform dimensionally, morphologically and mechanically upon exposure to non-mechanical external triggers. By leveraging these controllable transformations, these systems can be used as minimally invasive alternatives to implants and residence devices, foregoing the need for complex surgeries or endoscopies. 4D printing, the fabrication of 3D-printed structures that evolve their shape, properties, or functionality in response to stimuli over time, allows the production of such devices. This study explores the potential of volumetric printing, a novel vat photopolymerisation technology capable of ultra-rapid printing speeds, by comparing its performance against established digital light processing (DLP) printing in fabricating hydrogel-based drug-eluting devices. Six hydrogel formulations consisting of 2-(acryloyloxy)ethyl]trimethylammonium chloride solution, lithium phenyl-2,4,6-trimethylbenzoylphosphinate, varying molecular weights of the crosslinking monomer, poly(ethylene glycol) diacrylate, and paracetamol as a model drug were prepared for both vat photopolymerisation technologies. Comprehensive studies were conducted to investigate the swelling and water sorption profiles, drug release kinetics, and physicochemical properties of each formulation. Expandable drug-eluting 4D devices were successfully fabricated within 7.5 s using volumetric printing and were shown to display equivalent drug release kinetics to prints created using DLP printing, demonstrating drug release, swelling, and water sorption properties equivalent to or better than those of DLP-printed devices. The reported findings shed light on the advantages and limitations of each technology for creating these dynamic drug delivery systems and provides a direct comparison between the two technologies, while highlighting the promising potential of volumetric printing and further expanding the growing repertoire of pharmaceutical printing.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1595-1608"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and evaluation of a drug-in-adhesive patch for the transdermal delivery of ketoprofen.","authors":"Ran Bai, Miaomiao Yang, Xiaoyang Sun, Yanqin Hu, Kaiwen Chen, Xiaoyue Cui, Yinghua Sun, Tianhong Zhang","doi":"10.1007/s13346-024-01703-w","DOIUrl":"10.1007/s13346-024-01703-w","url":null,"abstract":"<p><p>The purpose of this study was to design a drug-in-adhesive (DIA) patch for transdermal delivery of ketoprofen, using hot-melt pressure-sensitive adhesive as the matrix of the patch. The adhesion properties and skin permeation of the patches were examined, and in vivo pharmacokinetics and tissue distribution of patches were evaluated. The novel ketoprofen patch with high adhesion was prepared by holt-melt method. The effects of different percentages of L-menthol on in vitro permeation were screened, 3% was added as the amount of permeation enhancer and the 24 h cumulative permeation amount(277.46 ± 15.58 µg/cm²) comparable to that of commercial patch MOHRUS^®(279.74 ± 29.23 µg/cm²). Pharmacokinetic and the tissue distribution study showed no matter in plasma, muscle or skin, the drug concentration of self-made ketoprofen patch was equivalent to that of commercial patch. These data indicated that the self-made patch provided a new reference for the development of ketoprofen dosage forms and promising alternative strategy for analgesic treatment.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1685-1692"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and optimization of a self micro-emulsifying drug delivery system (SMEDDS) for co-administration of sorafenib and curcumin.","authors":"Xingzhen Huang, Lizhen Feng, Xuefang Lu, Fan Yang, Shengjun Liu, Xueqian Wei, Jinping Huang, Yao Wang, Dongyi Huang, Tingting Huang","doi":"10.1007/s13346-024-01699-3","DOIUrl":"10.1007/s13346-024-01699-3","url":null,"abstract":"<p><p>In this study, we developed a novel co-administration of curcumin and sorafenib using a Self micro-emulsifying Drug Delivery System (SMEDDS) called Sorafenib-Curcumin Self micro-emulsifying Drug Delivery System (SOR-CUR-SMEDDS). The formulation was optimized using star point design-response surface methodology, and in vitro cellular experiments were conducted to evaluate the delivery ratio and anti-tumor efficacy of the curcumin and sorafenib combination. The SOR-CUR-SMEDDS exhibited a small size distribution of 13.48 ± 0.61 nm, low polydispersity index (PDI) of 0.228 ± 0.05, and negative zeta potential (ZP) of - 12.4 mV. The half maximal inhibitory concentration (IC₅₀) of the SOR-CUR-SMEDDS was 3-fold lower for curcumin and 5-fold lower for sorafenib against HepG2 cells (human hepatocellular carcinoma cells). Transmission electron microscopy (TEM) and particle size detection confirmed that the SOR-CUR-SMEDDS droplets were uniformly round and within the nano-emulsion particle size range of 10-20 nm. The SMEDDS were characterized then studied for drug release in vitro via dialysis membranes. Curcumin was released more completely in the combined delivery system, showing the largest in vitro drug release (79.20%) within 7 days in the medium, while the cumulative release rate of sorafenib in the release medium was low, reaching 58.96% on the 7 day. In vitro pharmacokinetic study, it demonstrated a significant increase in oral bioavailability of sorafenib (1239.88-fold) and curcumin (3.64-fold) when administered in the SMEDDS. These findings suggest that the SMEDDS formulation can greatly enhance drug solubility, improve drug absorption and prolong circulation in vivo, leading to increased oral bioavailability of sorafenib and curcumin.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1609-1625"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent progress in topical and transdermal approaches for melanoma treatment.","authors":"Alaleh Yourdkhani, Mehdi Esfandyari-Manesh, Paniz Ranjbaran, Mahdiyar Amani, Rassoul Dinarvand","doi":"10.1007/s13346-024-01738-z","DOIUrl":"10.1007/s13346-024-01738-z","url":null,"abstract":"<p><p>The global incidence of melanoma, the most lethal form of skin cancer, continues to escalate, emphasizing the urgent need for more effective therapeutic strategies. This review assesses the latest advancements in topical and transdermal drug delivery systems, positioning them as promising alternatives. These systems allow for the direct application of therapeutic agents to tumor sites, enhancing drug effectiveness, improving patient compliance, and reducing systemic toxicity. Specifically, innovations such as nanoparticles, microneedles, and vesicular systems are explored for their potential to optimize topical and localized drug delivery. By incorporating a graphical overview of these drug delivery vehicles, we visually underscore their roles in enhancing therapeutic outcomes across various treatment categories such as chemotherapy, immunotherapy, phototherapy, phytotherapy, and targeted therapy. This article critically evaluates recent breakthroughs, addresses the current challenges faced by researchers, and explores the future directions of topical and transdermal approaches in melanoma management. By presenting a summary of the latest research and predicting future trends, this review aims to inform ongoing developments and encourage further innovation in strategies for treating melanoma.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1457-1495"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}