Therapeutic deliveryPub Date : 2025-07-01Epub Date: 2025-06-03DOI: 10.1080/20415990.2025.2510889
Siddharth S Kesharwani, Casey L Sayre, Sharyu Kesharwani, Anna Burrows
{"title":"Quercetin-Eudragit® polymer complexes with enhanced loading, solubility, stability, and site-specific targeting.","authors":"Siddharth S Kesharwani, Casey L Sayre, Sharyu Kesharwani, Anna Burrows","doi":"10.1080/20415990.2025.2510889","DOIUrl":"10.1080/20415990.2025.2510889","url":null,"abstract":"<p><strong>Aim: </strong>Quercetin is a natural dietary compound known for its potential to prevent chronic diseases. However, the translation of this success to humans is hindered due to quercetin's poor oral bioavailability, attributed to its extremely low water solubility and permeability. These challenges affect the oral absorption of quercetin.</p><p><strong>Methods: </strong>The current work describes a polymer-based platform specifically targeted for the delivery of quercetin to the colon. Quercetin complexes were prepared using co-precipitation. The polymers used are Eudragit® S100/L100/L100-55. Ethanol and polyvinyl alcohol are the solvent and surfactant respectively in the complex formation process.</p><p><strong>Results: </strong>The formed polymer complexes demonstrate a high loading capacity, reaching approximately 315 μg/mL of quercetin. The complexes obtained were amorphous in the solid state and soluble in buffer with pHs > 5.5. The resulting Quercetin-Eudragit® complexes demonstrate significantly increased aqueous solubility, reaching concentrations > 1 mg/mL. The polymer complexes were more stable for > 30 h in aqueous solutions compared to quercetin. The solubilized Quercetin-Eudragit® formulations demonstrated enhanced reduction in cell viability in colon cancer cells HCT116 and HT29 when compared to quercetin.</p><p><strong>Conclusions: </strong>In summary, the study demonstrates the successful development of a polymer-quercetin complex with improved loading, solubility, stability, and targeted delivery properties.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"651-660"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209587","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":"Characterization of enteric-coated capsules filled with colchicine loaded zein nanoparticles for colon delivery.","authors":"Somayeh Taymouri, Somayeh Mirseyfifard, Fatemeh Shafiee","doi":"10.1080/20415990.2025.2520735","DOIUrl":"https://doi.org/10.1080/20415990.2025.2520735","url":null,"abstract":"<p><strong>Aim: </strong>In this study, we developed a dual pH and time-dependent formulation for targeted colonic release, aiming at minimizing adverse effect and enhancing anticancer efficacy of colchicine in the treatment of colorectal cancer.</p><p><strong>Materials and methods: </strong>To achieve this, colchicine was loaded in zein nanoparticles (Col-Z NP) which were further optimized and encapsulated in Eudragit S100 coated capsules. A full factorial design was employed to determine the optimal condition for preparation of Col-Z NP.</p><p><strong>Results: </strong>The optimized Col-Z NPs exhibited a spherical shape with particle size of 104.3 ± 1.6 nm, polydispersity index of 0.27 ± 0.01, zeta potential of 29.0 ± 0.1 mV, encapsulation efficiency of 59.8 ± 4.8%, release efficiency over 8 h of 45.5 ± 2.7%, and drug loading of 13.0 ± 0.0%. No notable difference in cytotoxicity was observed between free colchicine and Col-Z NPs at comparable concentrations. The cellular uptake study showed more uptake for coumarin 6 loaded Z NPs compared to free coumarin 6. Colchicine release from coated capsules was restricted to around 3% in gastric medium and increased to about 8% in simulated intestine medium, respectively.</p><p><strong>Conclusion: </strong>Results suggest that Eudragit S100 coated capsules containing Col-Z NP could be effective delivery system for colchicine to target colorectal tumors.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"1-17"},"PeriodicalIF":3.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508383","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}
{"title":"Intratympanic injection of emulsion-like dispersions to co-deliver cinnarizine and morin hydrate-lipoid E80 complex in a rabbit inner ear model.","authors":"Abhinab Goswami, Srikanth Ponneganti, Vijayakumar Gangipangi, Hariprasad Vavilala, Pullapanthula Radhakrishnanand, Sudhagar Selvaraju, Srinivasa Rao Mutheneni, Shreekant Bharti, Tamilvanan Shunmugaperumal","doi":"10.1080/20415990.2025.2516411","DOIUrl":"https://doi.org/10.1080/20415990.2025.2516411","url":null,"abstract":"<p><strong>Background: </strong>Drug delivery to perilymph after crossing the round window membrane is paramount important for inner ear disease management. Intratympanic (IT) injection of emulsion-like dispersions augments cinnarizine (CNZ) and morin hydrate (MH)-Lipoid E80 complex permeation into perilymph in a healthy rabbit inner ear model.</p><p><strong>Methods: </strong>A Box-Behnken design (BBD) followed by artificial neural network (ANN)-linked Levenberg - Marquardt (LM) algorithm was used for optimizing the injection formula. Immediately after 30-120 minutes post-IT injections, the concentration levels of CNZ and MH in both perilymph and plasma were monitored.</p><p><strong>Results: </strong>The ANN-linked LM algorithm displayed lower prediction and mean squared errors as well as higher correlation coefficient values for all responses when compared to the corresponding values shown by BBD. The IT injections possessed 156.8 ± 8.5 nm mean particle size, 42.70 ± 4.20 mV zeta potential, >98% CNZ and MH release within 10-20 minutes dissolution in pH 7.4 artificial perilymph solution, >97.26% cell viability in MTT assay and near normal histopathology. The 63.07 ± 23.62 µg/ml CNZ and 82.51 ± 8.33 µg/ml MH were attained in perilymph at 60 minutes post-IT injections.</p><p><strong>Conclusion: </strong>The IT-injected formulation can be used to co-deliver two drugs in perilymph for managing inner ear diseases.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"1-20"},"PeriodicalIF":3.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267275","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}
{"title":"Curcumin-loaded PEG-functionalized carbon nanotubes: a novel strategy for Alzheimer's management.","authors":"Shrutee Pawar, Vasanti Suvarna","doi":"10.1080/20415990.2025.2513213","DOIUrl":"https://doi.org/10.1080/20415990.2025.2513213","url":null,"abstract":"<p><strong>Aims: </strong>Curcumin (CUR) exhibits strong therapeutic potential for Alzheimer's disease due to its antioxidant, neuroprotective, anti-inflammatory, and anti-amyloid effects. However, its clinical application is limited by poor brain bioavailability. This study aimed to enhance CUR delivery to the brain via nasal administration using a novel formulation of polyethylene glycol (PEG)-functionalized carboxylated (COOH) Multi-Walled Carbon Nanotubes (MWCNT).</p><p><strong>Materials and methods: </strong>CUR-loaded MWCNT-COOH-PEG was developed and optimized using a 3<sup>2</sup> factorial design. The system was characterized for entrapment efficiency, particle size, zeta potential, and in vitro release. Neuroprotective efficacy was assessed through apoptosis inhibition in PC12 cells, and CUR concentration in the brain was measured post-nasal administration.</p><p><strong>Results: </strong>The formulation achieved an entrapment efficiency of 91.4 ± 0.8%, a zeta potential of -31.1 ± 1.05 mV, and a particle size of 310 ± 7.92 nm. In vitro release was 95.42 ± 0.0004% at pH 5.5 and 89.98 ± 0.0039% at pH 7.4. CUR at 18.75 µg/mL inhibited apoptosis in PC12 cells after 24 h. Higher brain CUR concentrations were observed 4 h post-administration.</p><p><strong>Conclusion: </strong>CUR-loaded MWCNT-COOH-PEG effectively enhances brain bioavailability of CUR, demonstrating significant neuroprotective effects, and offers a promising approach for Alzheimer's therapy.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"1-9"},"PeriodicalIF":3.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216930","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}
Therapeutic deliveryPub Date : 2025-06-01Epub Date: 2025-03-30DOI: 10.1080/20415990.2025.2484169
Tukaram Karanwad, Dimple S Lalchandani, Sachin B Jorvekar, Santa Mandal, Pawan Kumar Porwal, Roshan M Borkar, Subham Banerjee
{"title":"Pharmacokinetic assessment and level-A IVIVC establishment of rifampicin-loaded 3D printed tablets using SLS 3D printing.","authors":"Tukaram Karanwad, Dimple S Lalchandani, Sachin B Jorvekar, Santa Mandal, Pawan Kumar Porwal, Roshan M Borkar, Subham Banerjee","doi":"10.1080/20415990.2025.2484169","DOIUrl":"10.1080/20415990.2025.2484169","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the <i>in vitro</i> dissolution and <i>in vivo</i> absorption of rifampicin (RIF)-containing 3D-printed tablets using Selective Laser Sintering (SLS) technology.</p><p><strong>Methods: </strong><i>In vitro</i> dissolution was assessed in acidic (pH 1.2) and alkaline (pH 6.8) buffer media, while <i>in vivo</i> absorption was evaluated in a New Zealand White rabbit model. Both analytical and bioanalytical methods were rigorously developed and validated using LC-ESI-MS/MS, following ICH Q2 (R1) and FDA guidelines, respectively.</p><p><strong>Results: </strong>In the acidic medium, 16.22% of RIF was released within the first 2 h, whereas in the alkaline medium, the release increased to 41.75%, indicating a sustained release from the sintered 3D printed tablets. Pharmacokinetic parameters and their corresponding values of <i>C</i><sub><i>max</i></sub> (445.38 ± 193.62 ng/mL), <i>T</i><sub><i>max</i></sub> (02 ± 0.00 hr), <i>AUC</i><sub><i>0-t</i></sub> (841.51 ± 334.13 ng.h/mL), <i>AUC</i><sub><i>0-∞</i></sub> (861.66 ± 340.54 ng.h/mL), <i>K</i><sub><i>el</i></sub> (0.61 ± 0.13 h<sup>-1</sup>), and <i>t</i><sub><i>1/2</i></sub> (1.18 ± 0.25 hr) were obtained, demonstrating effective RIF absorption in the rabbit. Additionally, an <i>in vitro-in vivo</i> correlation (IVIVC) model was developed, demonstrating a good correlation between <i>in vitro</i> release and <i>in vivo</i> absorption, with R<sup>2</sup> value of 0.9696.</p><p><strong>Conclusion: </strong>The results underscore the potential of SLS 3DP technology in advancing the development of RIF-containing 3D printed tablets by sustaining <i>in vitro</i> dissolution following <i>in vivo</i> absorption profiles.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"535-544"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754191","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}
Therapeutic deliveryPub Date : 2025-06-01Epub Date: 2025-03-24DOI: 10.1080/20415990.2025.2478805
Ujjwal Gupta, Amit Kumar, Md Imtiyaz Alam, Paul Gajanan Balaji, Ankita Sharma, Awesh K Yadav
{"title":"Synthesis and characterization of protein nanohybrid systems for the brain delivery of Riluzole.","authors":"Ujjwal Gupta, Amit Kumar, Md Imtiyaz Alam, Paul Gajanan Balaji, Ankita Sharma, Awesh K Yadav","doi":"10.1080/20415990.2025.2478805","DOIUrl":"10.1080/20415990.2025.2478805","url":null,"abstract":"<p><strong>Aims: </strong>Synthesis and Characterization of Protein NanoHybrid Systems for the Brain Delivery of Riluzole.</p><p><strong>Methods/materials: </strong>Fullerene is converted into carboxylated fullerene (CF) and then, prepared RZU-loaded BSA nanoparticles conjugated with CF.</p><p><strong>Results: </strong>The particle size and zeta potential of RZU-PNH were found to be 210 ± 1.15 nm and -18.5 ± 0.615 mV respectively, and entrapment efficiency and loading efficiency of RZU-PNH were found to be 98.8 ± 0.53% and 11.6 ± 0.43%, respectively. The XRD of the RZU-PNH shows the amorphism behavior and CD revealed that secondary structure of the protein mainly consists of α-helix andβ-sheet. The MTT assay showed 88.60% and 90.84% cell viability in both SH-SY5Yand N2a cell lines at a concentration of 20 μg/ml and also, no significant nasal ciliotoxicity was observed after incubation with RZU-PNH.</p><p><strong>Conclusions: </strong>Obtained results indicated RZU-PNH formulation to treat amyotrophic lateral sclerosis.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"569-579"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693351","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}
Therapeutic deliveryPub Date : 2025-06-01Epub Date: 2025-03-16DOI: 10.1080/20415990.2025.2479416
Hetal P Thakkar, Ajay Unagar, Drashti Goinawala, Rushabh Panchal
{"title":"Formulation and characterization of Mirtazapine loaded mucoadhesive cubosomal in-situ gel for intranasal delivery.","authors":"Hetal P Thakkar, Ajay Unagar, Drashti Goinawala, Rushabh Panchal","doi":"10.1080/20415990.2025.2479416","DOIUrl":"10.1080/20415990.2025.2479416","url":null,"abstract":"<p><strong>Aims: </strong>The goal of the present investigation was to formulate and characterize the Cubosomal in-situ gel of Mirtazapine for intranasal delivery. The cubosomal preparation ensures higher entrapment of drug and delivery through intranasal route improves brain targeting of drug by avoiding the Blood Brain Barrier.</p><p><strong>Materials and methods: </strong>Cubosomes were prepared by bottom-up approach & Central Composite Design was used for optimization. In-situ thermosensitive gel was formulated by cold method and optimization was done based on gelation temperature and time. The optimized cubosomal formulation was evaluated for various parameters like vesicular size, entrapment efficiency, TEM analysis, in-vitro drug release and ex-vivo permeation study. The cubosomal in-situ gel was evaluated for gelling time, temperature, mucoadhesive and gelling strength.</p><p><strong>Results and conclusion: </strong>The optimized formulation exhibited 90.33% drug release which confirms that it exhibited superior drug release characteristic as compared to pure drug suspension. The optimized formulation was evaluated for nasal toxicity studies which assure its safety to nasal mucosal membrane. The <i>in-vivo</i> brain biodistribution study showed the Mirtazapine cubosomal in situ gel achieved higher brain concentrations compared to the oral suspension. The cubosomal in-situ gel of Mirtazapine seems to be a promising and safe approach for treatment of depression.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"545-553"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650902","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}
Therapeutic deliveryPub Date : 2025-06-01Epub Date: 2025-03-24DOI: 10.1080/20415990.2025.2478803
Nandeeni Punase, Ganesh V Jamdar, Ghanshyam Mapare, Vishal S Patil, Narendra Nagpure, Niharika Patil, Chandrakantsing V Pardeshi, Chandragouda R Patil
{"title":"In silico, in vitro, and in vivo assessment of chitosan-diltiazem nanoparticles against pulmonary fibrosis.","authors":"Nandeeni Punase, Ganesh V Jamdar, Ghanshyam Mapare, Vishal S Patil, Narendra Nagpure, Niharika Patil, Chandrakantsing V Pardeshi, Chandragouda R Patil","doi":"10.1080/20415990.2025.2478803","DOIUrl":"10.1080/20415990.2025.2478803","url":null,"abstract":"<p><strong>Aims: </strong>Diltiazem (DIL), a calcium channel blocker, has demonstrated potential ininhibiting fibrosis-related processes, including TGF-β activation, collagen production, and epithelial-mesenchymal transition, making it a promising candidate for idiopathic pulmonary fibrosis (IPF). This study evaluates the anti-fibrotic efficacy of DIL-loaded chitosan (DIL-CHT) and trimethyl chitosan (DIL-TMC) nanoparticles through molecular and experimental approaches.</p><p><strong>Methods: </strong>DIL-CHT and DIL-TMC nanoformulations were developed and analyzed particle size, ζ-potential, entrapment efficiency, and <i>in vitro</i> release. Antifibrotic efficacy in bleomycin (BLM)-induced IPF rat model, was tested at subtherapeutic doses (3 mg/kg/day, i.t.) and DIL alone (10 mg/kg/day, p.o.). DFT (B3LYP/6-31 G**) optimization and molecular docking were conducted to assess electronic properties and interactions among CHT, TMC, and DIL.</p><p><strong>Results: </strong>DIL-TMC and DIL-CHT nanoparticles were 175.6 nm and 267.8 nm, with entrapment efficiencies of 81.72% and 66.0%, respectively; TMC showed a superior 24-hour sustained release. TMC's larger HOMO-LUMO gap (ΔE = -0.260 eV vs. -0.253 eV for CHT) suggests greater stability, supporting its enhanced interaction with DIL. TMC nanoparticles significantly reduced BLM-induced IPF symptoms, i.e. BLM induced increased lung index, hydroxyproline accumulation, oxidative stress in lung tissue, and blood pressure.</p><p><strong>Conclusions: </strong>These findings indicate the strong therapeutic potential of DIL-TMC for IPF with minimal cardiovascular side effects.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"555-568"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693348","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}
Therapeutic deliveryPub Date : 2025-06-01Epub Date: 2025-03-25DOI: 10.1080/20415990.2025.2484170
Seyede Nazanin Zarneshan, Faranak Aghaz
{"title":"Engineered nanoparticles as a promising drug delivery system for glioblastoma multiforme treatment.","authors":"Seyede Nazanin Zarneshan, Faranak Aghaz","doi":"10.1080/20415990.2025.2484170","DOIUrl":"10.1080/20415990.2025.2484170","url":null,"abstract":"<p><p>Brain cancer has become an emerging medical disorder that poses a threat to human life due to the uncontrolled growth of cancer cells and their gradual spread to other organs. The most aggressive and life-threatening of the several types of Brain cancer is GBM. Treating GBM is difficult considering drugs are not exposed at the brain's site of action because of BBTB and BBB. Only a few cytotoxic drugs are presently used to treat GBM, including temozolomide, paclitaxel, and doxorubicin, and only temozolomide has enough BBB penetration. In this context, engineered nanoparticles are used to transport chemotherapeutic medications and reduce notable peripheral toxicity on normal cells; for necessary drug dosages. They are investigated as drug carriers to address the problem of drug resistance linked to traditional chemotherapy treatments. Many nanostructures, such as polymeric, lipid-based, and inorganic nanoparticles, have been developed as drug-delivery methods in recent decades. To be therapeutically successful as a GBM therapy, ENP formulations must diffuse through the BBB and efficiently deliver the drugs to the target cells. Various coatings and surface modifications of nanostructures can be tailored with different targeting moieties to facilitate the uptake of drug carriers by malignant cells while safeguarding healthy tissues from damage.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"593-606"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711325","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}