Samantha Mabvira, Sandile M Khamanga, Roderick B Walker
{"title":"Formulation and Characterization of a Fixed-Dose Microemulsion Containing Efavirenz, Emtricitabine, and Tenofovir.","authors":"Samantha Mabvira, Sandile M Khamanga, Roderick B Walker","doi":"10.1080/10837450.2025.2537128","DOIUrl":"https://doi.org/10.1080/10837450.2025.2537128","url":null,"abstract":"<p><p>Despite a marked decrease in HIV/AIDS-related mortality, HIV remains one of the leading causes of death in specific populations. Despite concerted efforts to find a cure for HIV, to date, none exists. Current antiretroviral therapy inhibits replication of the virus without completely eradicating it. The successful inhibition of viral replication is only achieved using a combination of antiretrovirals, which inhibit viral replication at different stages of the HIV lifecycle. Efavirenz (EFV), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) are one combination used for HIV management. The development of a novel fixed-dose microemulsion formulation of EFV, FTC and TDF was undertaken. Microemulsions (ME) were manufactured using phase titration and drug loading, particle size, transparency, Zeta potential and pH were determined. Transmission Electron Microscopy was used to visualize the microemulsion. In-vitro release testing was used to evaluate active pharmaceutical ingredient release behaviour. The optimized ME had an average Zeta potential of 33.8 mV and droplet size of 117 nm, determined using Dynamic Light Scattering and confirmed using Transmission Electron Microscopy. Powder X-ray diffraction and Differential Scanning Calorimetry analysis revealed the presence of a molecular dispersion of drugs. These findings demonstrate the potential value of using ME as a fixed-dose combination technology for the delivery of EFV, FTC and TDF.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-22"},"PeriodicalIF":2.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel Vanillic Acid-Loaded <i>In Situ</i> Gels: Development, Characterization, <i>In Vitro</i> Evaluation for Enhanced Wound Healing and Skin Irritation Test.","authors":"Gökçe Mutlu Sonat, Emre Şefik Çağlar, Dilara Güreşçi, Ahmet Aydın, Hande Sipahi, Neslihan Üstündağ Okur","doi":"10.1080/10837450.2025.2534867","DOIUrl":"https://doi.org/10.1080/10837450.2025.2534867","url":null,"abstract":"<p><p>This study aimed to develop <i>in situ</i> gel formulations containing vanillic acid to enhance patient compliance and accelerate wound healing. Vanillic acid-loaded <i>in situ</i> gels were prepared and their physicochemical properties were evaluated through <i>in vitro</i> release and <i>ex vivo</i> permeation studies. Additionally, antioxidant capacity, cytotoxicity, wound healing, prostaglandin E2 levels, IL-6 inhibition and skin irritation tests were conducted. The optimized IN3-VA formulation exhibited a gelling temperature of 32.394 ± 0.842, a pH value of 4.780 ± 0.010 and a viscosity of 2473.33 ± 11.54 cP. It demonstrated specific mechanical properties, including hardness of 27.94 ± 1.30 g and adhesiveness of -97.00 ± 14.60 g.mm. The IN15-VA formulation showed improved parameters, with a hardness of 38.84 ± 3.33 g, adhesiveness of -126.35 ± 22.78 g.mm, pH value of 4.870 ± 0.010, viscosity of 3853.33 ± 30.55 cP and a gelling temperature of 31.854 ± 0.345. Both formulations demonstrated sustained release behavior, releasing 60% of the medication <i>in vitro</i> over 6 hours with no cytotoxic effects. They also decreased copper ion reduction and the release of nitric oxide, with cellular proliferation rates of 63% for IN3-VA and 73% for IN15-VA. Moreover, IN15-VA significantly reduced prostaglandin E2 levels, controlled IL-6 increase and exhibited non-irritating properties. The results suggest that these vanillic acid-loaded <i>in situ</i> gels hold promising potential in wound treatment due to their sustained release over 48 hours.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-25"},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oyunchimeg Zandraa, Fahanwi Asabuwa Ngwabebhoh, Smarak Bandyopadhyay, Nabanita Saha, Tomas Saha, Petr Saha
{"title":"Self-assembled mumio-stabilized bioactive gel systems for topical therapeutics of rheumatoid arthritis: structural, rheological, cytocompatibility, and antimicrobial properties.","authors":"Oyunchimeg Zandraa, Fahanwi Asabuwa Ngwabebhoh, Smarak Bandyopadhyay, Nabanita Saha, Tomas Saha, Petr Saha","doi":"10.1080/10837450.2025.2529894","DOIUrl":"10.1080/10837450.2025.2529894","url":null,"abstract":"<p><p>This study presents the development of salicylate polyacrylic copolymer gel systems incorporating mumio particulates as a bioactive agent for the topical treatment of rheumatoid arthritis. Using an experimental design, formulations were optimized based on mumio, salicylic acid, and polyacrylate copolymer ratios. Rheological behavior was assessed through frequency, temperature, and time sweep tests to evaluate shear response, stability, and application suitability. Spectral and morphological analyses confirmed the uniformity and surface characteristics of the gels. Antimicrobial activity was tested against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger. Cytotoxicity was evaluated using NIH-3T3 mouse fibroblast cells. Results showed over 60% microbial inhibition after 24 hours and maintained cell viability above 70% at both 24 and 48 hours, indicating good biocompatibility. The gels also exhibited smooth texture, consistent bioactive dispersion, and non-irritating properties. Overall, these findings support the potential of mumio-loaded salicylate-polyacrylic gels as stable, biocompatible, and effective topical therapeutics for rheumatoid arthritis.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-14"},"PeriodicalIF":2.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design and development of leflunomide loaded topical microsponge gel: insights from <i>ex vivo</i> and <i>in vivo</i> inflammatory studies.","authors":"Nirmal Shah, Priyank Patel, Dipti Gohil, Rajesh Maheshwari, Chitrali Talele, Dipali Talele, Dhaivat Parikh, Jay Patwa","doi":"10.1080/10837450.2025.2525256","DOIUrl":"10.1080/10837450.2025.2525256","url":null,"abstract":"<p><p>Leflunomide, a frequently used medicament, falls under the category of disease modifying anti-rheumatoid drugs. The tablets are the only product available in the market which may lead to liver toxicity upon long-term use. Being a class II drug, there is a need of some novel formulation for minimizing systemic toxicity of drug without compromising its therapeutic potential. Microsponges possess unique characteristics that makes it a versatile drug delivery carrier. Leflunomide loaded Microsponges were prepared with matrix forming polymer (ethyl cellulose) and stabilizer (poly vinyl alcohol) using quasi-emulsion solvent diffusion method. Two independent parameters, namely concentrations of polymer and stabilizing agent, were examined using a full 3<sup>2</sup> factorial design to determine their impact on particle size and % entrapment efficiency. The optimized formulation showed promising result for particle size (48.96 µm) and entrapment efficiency (89.45%) with spherical and tiny pores on surface. The optimized gel exhibited sustained release up to 8 h (91.46 ± 3.84%) with satisfactory results of flux and permeability coefficient. The developed formulation has good anti-inflammatory properties in wistar rats and a histopathology investigation on rats' skin verified its skin compatibility. The stability study showed stable formulation up to the period of 3 months. These findings demonstrated the potential of microsponges to improve the therapeutic potential of poorly soluble leflunomide.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-12"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineered gastroretentive amorphous ferulate matrix: a novel raft-forming paradigm for enhanced bioavailability.","authors":"Ruedeekorn Wiwattanapatapee, Nattawat Chavasiri, Kijja Laohawiriyakamon, Saravoot Pumjan, Nattawut Leelakanok, Arpa Petchsomrit","doi":"10.1080/10837450.2025.2525265","DOIUrl":"10.1080/10837450.2025.2525265","url":null,"abstract":"<p><p>This study aimed to enhance the solubility of ferulic acid using solid dispersion techniques and develop chewable tablets that neutralize stomach acid, form a protective gel layer, prevent gastric fluid reflux, and ensure prolonged retention in the stomach with controlled release of the active ingredient. Researchers developed solid dispersions of ferulic acid using Eudragit<sup>®</sup> E PO as a carrier, with a 1:2 w/w ratio, achieving the highest solubility (39.9 mg/mL). Chewable tablets were formulated by direct compression, incorporating sodium alginate as a gelling agent, calcium carbonate for calcium ions and carbon dioxide, HPMC as a release retardant, and mannitol as a diluent. All formulations rapidly formed a gel layer within 10 s, had a lower density than gastric fluid, and floated on 0.1 N hydrochloric acid for over 8 h. The optimal formulation demonstrated excellent physical properties, including a gel strength of 11.84 g, an acid neutralization capacity of 15.97 mEq, and reaching 80.58% over 8 h with gradual release. It exhibited significant antioxidant activity (IC<sub>50</sub> 6.74 µg/mL) in the DPPH assay and showed stronger anti-inflammatory effects in macrophage cells than indomethacin. These findings suggest this formulation could enhance ferulic acid's effectiveness in treating gastric ulcers and preventing acid reflux.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-16"},"PeriodicalIF":2.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Janhavi Deshmukh, Kavish Sanil, Achref Cherif, Eman A Ashour
{"title":"Development of fenofibrate solid dispersion via hot melt extrusion and 3D printing technologies.","authors":"Janhavi Deshmukh, Kavish Sanil, Achref Cherif, Eman A Ashour","doi":"10.1080/10837450.2025.2522802","DOIUrl":"10.1080/10837450.2025.2522802","url":null,"abstract":"<p><p>This study aimed to develop an amorphous solid dispersion (ASD) of fenofibrate using Hot Melt Extrusion (HME) and 3D printing to evaluate the impact of preparation methods on ASD properties. Fenofibrate (10% w/w) was processed with Soluplus<sup>®</sup> and Polyethylene oxide-N80 to produce HME filaments. These filaments were either used as feedstock for Fused Deposition Modeling (FDM) 3D printing to fabricate tablets with 90%, 70%, and 50% infill densities or milled and filled into gelatin capsules. Printability was assessed <i>via</i> a three-point bend test. The fenofibrate formulations were evaluated for drug content, physical state, surface morphology, and release profile. The SEM images of pure fenofibrate showed large cylindrical crystals while the 3D-printed tablets showed a smooth surface with no record of any crystals. This observation is in line with the DSC results and confirms the conversion of fenofibrate from crystalline to an amorphous state. The <i>in- vitro</i> drug release for the 3D printed tablets and capsules was increased 2-fold as compared to pure fenofibrate. Statistical comparisons further supported these findings, highlighting infill density as a tunable parameter for modulating release kinetics.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruyue Dong, Xiaolu Han, Zhiqiang Tang, Xiaoxuan Hong, Hui Zhang, Nan Liu, Kun Wan, Mingyuan Li, Zengming Wang, Aiping Zheng
{"title":"Study on controlling 3D printed drug release rates based on model structural adjustment.","authors":"Ruyue Dong, Xiaolu Han, Zhiqiang Tang, Xiaoxuan Hong, Hui Zhang, Nan Liu, Kun Wan, Mingyuan Li, Zengming Wang, Aiping Zheng","doi":"10.1080/10837450.2025.2522795","DOIUrl":"10.1080/10837450.2025.2522795","url":null,"abstract":"<p><p>As an emerging technology, 3D printing facilitates the fabrication of complex preparations and enables controlled drug release. This study integrated semi-solid extrusion (SSE) and fused deposition modeling (FDM) to develop core-shell structured sustained-release tablets (CSRT) with varying release profiles, exploring how structural design influences release behavior. Propranolol hydrochloride was selected as the model drug. Drug-loaded cores with different filling rates were prepared using SSE and characterized for appearance, hardness, XRD, and release properties. Shells with varying release windows were fabricated using FDM. Subsequently, shells and cores were assembled. Micro-CT was employed for microstructural characterization, while drug assay and release properties were assessed. The results indicated that cores exhibited a good appearance, and the SSE process had no effect on the crystal type. Adjusting the filling rate allowed for slight modulation of drug release while the shell structure effectively prolonged drug release. The CSRT displayed no significant internal defects, and the assay met the United States Pharmacopoeia-National Formulary 2024 (USP-NF 2024) requirements. Adjusting release windows resulted in a sustained release ranging from 8 to 24 h, with the release profile conforming to first-order kinetics (R<sup>2</sup> values ranging from 0.961 to 0.999). These findings provide practical strategies for controlling drug release rates.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-12"},"PeriodicalIF":2.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Midhat Rehman, Saba Sohail, Zakir Ali, Ali H Alamri, Ahmed A Lahiq, Taha Alqahtani, Saleh Alyahya, Fakhar Ud Din
{"title":"Development and optimization of cilostazol loaded transethosomal gel for improved performance.","authors":"Midhat Rehman, Saba Sohail, Zakir Ali, Ali H Alamri, Ahmed A Lahiq, Taha Alqahtani, Saleh Alyahya, Fakhar Ud Din","doi":"10.1080/10837450.2025.2521055","DOIUrl":"10.1080/10837450.2025.2521055","url":null,"abstract":"<p><p>Deep vein thrombosis (DVT) is the third major leading cause of mortality and morbidity after cardiovascular disease and stroke. Cilostazol (CLZ) being one of the antiplatelet agents is effectively used in DVT. However, its oral administration is associated with several problems, such as gastrointestinal side effects and extensive first-pass metabolism. Herein, CLZ-loaded transethosomes (CLZ-TEs) were prepared and incorporated in chitosan gel (CLZ-TEG) for transdermal administration. Box-Behnken Design Expert<sup>®</sup> software was used to statistically optimize CLZ-TEs. Particle properties, Transmission electron microscopy (TEM), and Fourier Transform Infrared spectroscopy (FTIR) analyses of CLZ-TEs were accomplished followed by <i>in vitro</i> release and permeation studies and its comparison with CLZ-TEG, CLZ-dispersion (Ds) and CLZ-G. Moreover, skin irritation and pharmacokinetics studies of the optimized CLZ-TEG were executed. The optimized CLZ-TEs showed a mean particle size of 174 nm, polydispersity index of 0.173, zeta potential of -30 mV, and entrapment efficiency of 99%. TEM exhibited spherical nanovesicles and FTIR demonstrated compatibility of the excipients. Moreover, CLZ-TEG was homogeneous, smooth, and spreadable. Similarly, CLZ-TEG displayed sustained release and enhanced permeation of the CLZ. Furthermore, pharmacokinetic study showed significantly improved (<i>p</i> < 0.05) bioavailability of CLZ-TEG when compared with CLZ-G and CLZ-Ds. It was concluded that CLZ-TEG may be a potential candidate for the management of DVT.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-19"},"PeriodicalIF":2.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigating the <i>in vivo</i> distribution characteristics of gel-in-water nanogel emulsions and demonstrating their efficacy in treating C26 tumor-bearing mice.","authors":"Yi Zhang, Jannatul Fardous, Ryota Doi, Yuuta Inoue, Yasuhiro Ikegami, Hiroyuki Ijima","doi":"10.1080/10837450.2025.2518564","DOIUrl":"10.1080/10837450.2025.2518564","url":null,"abstract":"<p><p>Nanotechnology has been advancing drug delivery systems (DDSs) for decades. Nanoparticle DDSs, in which nanometric carriers deliver drugs to the target site, are highly valued for cancer treatment. In this study, based on nanoemulsion technology, gel-in-water (G/W) nanoemulsion was developed by using an organogel, i.e. 12-hydroxystearic acid and castor oil, followed by encapsulation of the model anticancer drug paclitaxel (PTX) within the nanogel droplets. The G/W was prepared using ultrasound and stabilized with a nonionic surfactant. The enhanced permeability and retention of G/W were investigated by encapsulating coumarin-6 and comparing it with an oil-in-water (O/W) nanoemulsion. Temporal changes in tissue distribution of both nanoemulsions were used to assess the effect of gelation on drug distribution. Regardless of the tissue type, the extraction efficiency of G/W was lower compared to O/W. The fluorescence intensity of coumarin-6 in G/W was higher compared to O/W. The size of G/W nanoparticles affects lung distribution and blood retention. PTX-loaded G/W (PTX-G/W) nanoparticles effectively treated colon cancer <i>in vivo</i>. They also exhibited antitumor activity against colon26 (C26) cells <i>in vitro</i>. The impact of particle size on the <i>in vivo</i> tissue distribution of G/W nanoemulsions suggests an improvement in drug delivery to the tumor site <i>via</i> nanoparticles.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-14"},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing darunavir delivery: nanoformulation strategies and innovations in HIV therapy.","authors":"Shreyash R Patil, Anjana Adhyapak, Rahul Koli","doi":"10.1080/10837450.2025.2520624","DOIUrl":"10.1080/10837450.2025.2520624","url":null,"abstract":"<p><p>Darunavir, a nonpeptidic protease inhibitor, remains a cornerstone of antiretroviral therapy due to its potent activity against wild-type human immunodeficiency virus (HIV). However, its poor aqueous solubility and limited oral bioavailability, characteristic of Biopharmaceutical Classification System Class II drugs, restrict therapeutic efficacy, with an absorption rate of only 37%. To address these pharmacokinetic limitations, nanotechnology-based strategies have been explored to enhance drug solubility, systemic exposure, and targeted tissue distribution. This review critically examines the potential of nanocarrier-based formulations, including solid lipid nanoparticles, supersaturated self-nanoemulsifying drug delivery systems, lipid nanoemulsions, poly(lactic-co-glycolic acid) nanoparticles, and cubosomes, in optimizing darunavir pharmacokinetics. These approaches have demonstrated improved bioavailability, sustained drug release, lymphatic targeting, and enhanced blood-brain barrier penetration, offering promising avenues for optimizing HIV therapy while minimizing systemic toxicity. Further, this review discusses challenges associated with nanoformulation-based antiretroviral strategies, scalability, manufacturing challenges, potential toxicity, immunogenicity, long-term stability issues, and explores emerging innovations, such as multifunctional nanoparticles, targeted delivery platforms, and sustainable nanotechnology-based formulations. By systematically evaluating current advances, this analysis provides critical insights into overcoming bioavailability constraints and facilitating the clinical translation of nanocarrier-based antiretroviral therapies.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-49"},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}