Pharmaceutical Development and Technology最新文献

{"title":"Dwell time on tableting: dwell time according to force versus geometric dwell time.","authors":"Valentyn Mohylyuk","doi":"10.1080/10837450.2024.2384446","DOIUrl":"10.1080/10837450.2024.2384446","url":null,"abstract":"<p><p>Dwell time is an important parameter responsible for the material deformation and the mechanical and biopharmaceutical properties of the tablet. Thus, it is widely used for scale-up purposes. The geometric dwell time (GDT) can be assumed based on the shape of the punch head and the diameter and speed of the turret. This research is aimed to compare compaction simulator-recorded dwell time according to force (DTF) and the GDT calculated for the simulated rotary tablet press using the microcrystalline cellulose and calcium phosphate mixtures (CEOLUS™ UF-711 and DI-CAFOS^® A60) in different proportions. Tablets were prepared, and DTF was analyzed with a compaction simulator (STYL'One Nano and Alix software) upon simulating a small rotary press at 70 rpm and a compression pressure of 10-50 kN (100-500 MPa). While GDT comprised of 14.4 ms, DTF was compression force and formulation dependent. The differences between the DTF values of the formulations decreased as the compression force increased, which was most pronounced at compression forces of 10 and 15 kN.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"719-726"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752371","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":"Extracellular vesicle-based formulation of doxorubicin: drug loading optimization, characterization, and cytotoxicity evaluation in tumor spheroids.","authors":"Fatemeh Mehryab, Marzieh Ebrahimi, Hossein Baharvand, Azadeh Haeri, Faezeh Shekari","doi":"10.1080/10837450.2024.2384448","DOIUrl":"10.1080/10837450.2024.2384448","url":null,"abstract":"<p><p>Doxorubicin (DOX) is a chemotherapeutic with considerable efficacy, but its application is limited due to cardiotoxicity. Nanoparticles can improve DOX efficacy and prevent its adverse effects. Herein, DOX-loaded extracellular vesicles (DOX-EVs) were prepared using different loading methods including incubation, electroporation, and sonication in different hydration buffers to permeabilize nanostructures or desalinize DOX for improved entrapment. Different protein:drug (µg:µg) ratios of 1:10, 1:5, and 1:2, and incubation parameters were also investigated. The optimal formulation was characterized by western blotting, electron microscopy, Zetasizer, infrared spectroscopy, and release study. The cellular uptake and efficacy were investigated in MCF-7 spheroids <i>via</i> MTS assay, spheroid formation assay (SFA), confocal microscopy, and flow cytometry. The percentage of entrapment efficiency (EE) of formulations was improved from 1.0 ± 0.1 to 22.0 ± 1.4 using a protein:drug ratio of 1:2 and sonication in Tween 80 (0.1%w/v) containing buffer. Characterization studies verified the vesicles' identity, spherical morphology, and controlled drug release properties. Cellular studies revealed the accumulation and cytotoxicity of DOX-EVs in the spheroids, and SFA and confocal microscopy confirmed the efficacy and cellular localization. Flow cytometry results revealed a comparable and amplified efficacy for DOX-EV formulations with different cell origins. Overall, the EV formulation of DOX can be applied as a promising alternative with potential advantages.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"727-737"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788844","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":"Impact of surfactant raw material variability on extrudate clarity appearance (transparency) in HME continuous manufacturing.","authors":"Claudia A Lohmann, Esther Bochmann, Samuel O Kyeremateng","doi":"10.1080/10837450.2024.2378333","DOIUrl":"10.1080/10837450.2024.2378333","url":null,"abstract":"<p><p>The appearance of an extrudate formulation was monitored during hot-melt extrusion (HME) continuous manufacturing over 3 days. The formulation matrix consisted of a polymeric component, copovidone, and a low molecular weight surfactant, polysorbate 80. Based on studies prior to the continuous manufacturing, the desired appearance of the target extrudate is translucent. Although process parameters such as feed rate and screw speed were fixed during the continuous manufacturing, the extrudate appearance changed over time from turbid to translucent. For root-cause investigation, the extrudates were analyzed offline by differential scanning calorimetry (DSC) and advanced polymer chromatography (APC^™). Although the polysorbate 80 content of both turbid and translucent extrudates was within target, the glass transition temperature of the turbid extrudate was 2 °C above expected value. The observed turbidity was traced to lot-to-lot variability of the polysorbate 80 used in the continuous manufacturing, where APC^™ analysis revealed that the relative content of the low molecular weight component varied from 23% to 27% in correlation with the evolution from turbid to translucent extrudates. This work stresses the importance of taking feeding material variability into account during continuous manufacturing.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"684-690"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591015","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":"Formulation and statistical optimization of letrozole loaded nanotransferosomal gel for tumor targeting.","authors":"Sara Imtiaz, Saba Sohail, Fakhar Ud Din, Zakir Ali, Sibgha Batool, Maimoona Malik, Asif Nawaz, Ali H Alamri, Ahmed A Lahiq, Shaker T Alsharif, Abdullah Asiri","doi":"10.1080/10837450.2024.2382437","DOIUrl":"10.1080/10837450.2024.2382437","url":null,"abstract":"<p><p>Letrozole (LTZ) is used as first-line treatment for hormone-positive breast cancer (BC) in postmenopausal women. However, its poor aqueous solubility and permeability have reduced its clinical efficacy. Herein, we developed LTZ-nanotransferosomes (LTZ-NT) to address above mentioned issues. The LTZ-NT were optimized statistically using Design Expert^® followed by their characterization <i>via</i> dynamic light scattering (DLS), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and Differential scanning calorimetry (DSC). The optimized LTZ-NT was incorporated into 1% chitosan-gel to develop LTZ-NTG. Moreover, <i>in vitro</i> drug release and <i>ex vivo</i> permeation of LTZ-NTG were performed and compared with LTZ-dispersion and LTZ-NT. Additionally, skin irritability and histopathology of LTZ-NTG were investigated. Furthermore, <i>in vitro</i> antitumor study of LTZ-NTG was investigated in BC cell lines. The optimized LTZ-NT showed suitable zeta potential (30.4 mV), spherical size (162.5 nm), and excellent entrapment efficiency (88.04%). Moreover, LTZ-NT exhibited suitable thermal behavior and no interactions among its excipients. In addition, LTZ-NTG had an optimal pH (5.6) and a suitable viscosity. A meaningfully sustained release and improved permeation of LTZ was observed from LTZ-NTG. Additionally, LTZ-NTG showed significantly enhanced cell death of MCF-7 and MCC-7 cells. It can be concluded that LTZ-NTG has the potential to deliver chemotherapeutic agents for possible treatment of BC.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"703-718"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634207","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":"Quercetin nanocrystals for bioavailability enhancement: impact of different functional stabilizers on <i>in vitro</i>/<i>in vivo</i> drug performances.","authors":"Yuwen Zhu, Fei Hu, Chengying Shen, Baode Shen, Hailong Yuan","doi":"10.1080/10837450.2024.2361654","DOIUrl":"10.1080/10837450.2024.2361654","url":null,"abstract":"<p><p>The purpose of this study was to investigate the impact of different functional stabilizers on <i>in vitro/in vivo</i> drug performances after oral administration of drug nanocrystals. Quercetin nanocrystals (QT-NCs) respectively stabilized by five types of functional stabilizers, including hydroxypropyl methyl cellulose E15 (HPMC E15), poloxamer 407 (P407), poloxamer 188 (P188), D-α-tocopherol polyethylene glycol succinate (TPGS), and glycyrrhizin acid (GL), were fabricated by wet media milling technique. The particle size, morphology, physical state, drug solubility, drug dissolution <i>in vitro</i>, and orally pharmacokinetic behaviors of all QT-NCs were investigated. All QT-NCs with similar particle size about 200 nm were obtained by controlling milling speed and milling time. No significant differences in particles shape and crystalline nature were found for QT-NCs stabilized by different functional stabilizers. But the solubility and dissolution of QT-NCs were significantly influenced by the different functional stabilizers. The AUC_0∼<i>_t</i> of all QT-NCs after oral administration was in the following order: QT-NCs/P188 ≈ QT-NCs/HPMC E15 > QT-NCs/GL > QT-NCs/P407 ≈ QT-NCs/TPGS, and the <i>C</i>_max showed an order of QT-NCs/P407 > QT-NCs/P188 ≈ QT-NCs/GL > QT-NCs/HPMC E15 > QT-NCs/TPGS. Both of QT-NCs/P407 and QT-NCs/TPGS exhibited faster oral absorption with <i>T</i>_max at 0.5 h and 0.83 h, respectively, while the other three QT-NCs (QT-NCs/P188, QT-NCs/GL and QT-NCs/HPMC E15) showed a relatively slow absorption with same <i>T</i>_max at 5.33 h. The longest MRT_0∼<i>_t</i> (11.72 h) and <i>t</i>_1/2z (32.22 h) were observed for QT-NCs/HPMC E15. These results suggested that the different functional stabilizers could significantly influence on drug solubility, drug dissolution <i>in vitro</i> and orally pharmacokinetic behavior of QT-NCs, and it is possible to alter the drug dissolution <i>in vitro</i>, oral absorption and drug retention <i>in vivo</i> by changing the type of functional stabilizers in NCs preparation.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"551-558"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162251","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":"Preparation and anti-tumor activity of paclitaxel silk protein nanoparticles encapsulated by biofilm.","authors":"Yating Ji, Junxu Hao, Xu Tao, Zhihang Li, Lijiang Chen, Na Qu","doi":"10.1080/10837450.2024.2376075","DOIUrl":"10.1080/10837450.2024.2376075","url":null,"abstract":"<p><p>In order to overcome the poor bioavailability of paclitaxel (PTX), in this study, self-assembled paclitaxel silk fibronectin nanoparticles (PTX-SF-NPs) were encapsulated with outer membrane vesicles of Escherichia coli (E. coil), and biofilm-encapsulated paclitaxel silk fibronectin nanoparticles (OMV-PTX-SF-NPs) were prepared by high-pressure co-extrusion, the size and zeta potential of the OMV-PTX-SF-NPs were measured. The antitumor effects of OMV-PTX-SF-NPs were evaluated by cellular and pharmacodynamic assays, and pharmacokinetic experiments were performed. The results showed that hydrophobic forces and hydrogen bonding played a major role in the interaction between paclitaxel and filipin proteins, and the size of OMV-PTX-SF-NPs was 199.8 ± 2.8 nm, zeta potential was -17.8 ± 1.3 mv. The cellular and in vivo pharmacokinetic assays demonstrated that the OMV-PTX-SF-NPs possessed a promising antitumor effect. Pharmacokinetic experiments showed that the AUC0-∞ of OMV-PTX-SF-NPs was 5.314 ± 0.77, which was much larger than that of free PTX, which was 0.744 ± 0.14. Overall, we have successfully constructed a stable oral formulation of paclitaxel with a sustained-release effect, which is able to effectively increase the bioavailability of paclitaxel, improve the antitumor activity, and reduce the adverse effects.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"627-638"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555246","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":"An overview on recent approaches for colonic drug delivery systems.","authors":"Aylin Deljavan Ghodrati, Tansel Comoglu","doi":"10.1080/10837450.2024.2362353","DOIUrl":"10.1080/10837450.2024.2362353","url":null,"abstract":"<p><p>Colon-targeted drug delivery systems have garnered significant interest as potential solutions for delivering various medications susceptible to acidic and catalytic degradation in the gastrointestinal (GI) tract or as a means of treating colonic diseases naturally with fewer overall side effects. The increasing demand for patient-friendly drug administration underscores the importance of colonic drug delivery, particularly through noninvasive methods like nanoparticulate drug delivery technologies. Such systems offer improved patient compliance, cost reduction, and therapeutic advantages. This study places particular emphasis on formulations and discusses recent advancements in various methods for designing colon-targeted drug delivery systems and their medicinal applications.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"566-581"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174862","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":"Development of thermosensitive liposome-containing in-situ gel systems for intranasal administration of thiocolchicoside and in vivo evaluation in a rabbit model.","authors":"Burcu Uner, Juste Baranauskaite Ortasoz, Cetin Tas","doi":"10.1080/10837450.2024.2364707","DOIUrl":"10.1080/10837450.2024.2364707","url":null,"abstract":"<p><strong>Aim: </strong>Thiocolchicoside (THC) is a drug under the category of BCS III. Due to its high molecular weight, it has poor oral bioavailability and low skin permeability. This study aims to find an alternative delivery method for THC that enhances its bioavailability through nasal application approach. <i>In situ</i> gels containing plain or liposomal THC with different combinations of Pluronic® F127 and PEG 400 were prepared.</p><p><strong>Method: </strong>Liposome formulations were prepared using the thin film hydration method and tested for their characterization such as for drug content, particle size, and zeta potential. <i>In vivo</i> pharmacokinetic parameters of formulations such as C_max, T_max, and AUC were tested on the rabbit model. The formulations were also scrutinized for their cell viability properties.</p><p><strong>Result: </strong>Formulation composition with 2% soybean phosphatidylcholine and 10 mg THC exhibited ∼94% entrapment efficiency, minimum particle size 101.32 nm, low polydispersity index 0.225 and +0.355 zeta potential. <i>In situ</i> liposomal dispersion containing 15% Pluronic® F127 turned into gel at nasal temperature. Cell lines were unharmed for 48 h. İn situ liposomal gels showed 1.5x higher blood concentration than the control formula.</p><p><strong>Conclusion: </strong><i>In situ</i> gels of liposomal THC formulations offer advantages over traditional nasal solutions, demonstrating comparable bioavailability to parenteral medication while also preserving the health of nasal mucosa cells.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"582-595"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261273","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":"Intranasal delivery of doxepin: enhancing brain targeting efficiency utilizing nanostructured lipid carriers for a biopharmaceutics drug disposition classification system class-I drug.","authors":"Hetal P Patel, Ayushi V Vasandia, Rahul Jha, Bhargavi V Desai, Ditixa T Desai, Praful P Dedhiya, Bhavin A Vyas, Furqan A Maulvi","doi":"10.1080/10837450.2024.2376102","DOIUrl":"10.1080/10837450.2024.2376102","url":null,"abstract":"<p><p>Doxepin, a Class-I Biopharmaceutics Drug Disposition Classification System (BDDCS) drug, exhibits poor bioavailability due to extensive first-pass metabolism. This research focuses on enhancing the delivery of doxepin by formulating nanostructured lipid carriers (NLCs) through the utilization of the Box-Behnken Design methodology. These optimized NLCs are intended for intranasal administration, with the ultimate goal of improving nose-to-brain drug delivery. NLCs were formulated using a high-speed homogenization technique. The optimized batch had a small particle size (75.80 ± 5.48 nm, PDI = 0.286), high entrapment efficiency (94.10 ± 0.16%), and sustained <i>ex vivo</i> release (82.25 ± 4.61% at 24 h). Characterization studies confirmed the conversion of doxepin from a crystalline to an amorphous state with uniform distribution in the lipid matrix. <i>In vivo</i> pharmacokinetic studies in rats showed significantly higher doxepin concentration in the brain tissue (C_max = 16.77 µg/g, t_max = 30 min) after intranasal administration compared to intravenous administration (C_max = 2.53 µg/g, t_max = 6 h). High-drug targeting efficiency (DTE = 284.3%) and direct transport percentage (DTP = 64.8%) suggested direct penetration of NLCs in the brain <i>via</i> olfactory and trigeminal pathways. In conclusion, the study highlights the potential of NLCs to improve the bioavailability of doxepin through nose-to-brain delivery and thereby potentially enable the treatment of neurological disorders.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"639-647"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559388","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":"Targeted pH-responsive delivery of rosmarinic acid <i>via</i> phenylboronic acid functionalized mesoporous silica nanoparticles for liver and lung cancer therapy.","authors":"Muhammad Kawish, Nimra Naz Siddiqui, Humera Jahan, Abdelbari Elhissi, Hina Zahid, Bushra Khatoon, Muhammad Raza Shah","doi":"10.1080/10837450.2024.2356210","DOIUrl":"10.1080/10837450.2024.2356210","url":null,"abstract":"<p><p>Currently, chemotherapy is one of the most practiced approaches for the treatment of cancers. However, existing chemotherapeutic drugs have poor aqueous solubility, poor selectivity, higher systematic toxicity, and poor target accumulation. In this study, we designed and synthesized a boronic acid/ester-based pH-responsive nano-valve that specifically targets the microenvironment in cancer cells. The nano-valve comprises phenylboronic acid-coated mesoporous silica nanoparticles (B-MSN) loaded with polyphenolic compound Rosmarinic acid (ROS-B-MSN). The nano-valve was further coated with lignin (LIG) to achieve our desired LIG-ROS-BMSN nano-valve for targeted chemotherapy against Hep-G2 and NCI-H460 cell lines. The structure and properties of NPs were characterized by Fourier-transformed infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM) in combination with EDX, and Dynamic light scattering (DLS). The outcomes revealed that the designed LIG-ROS-BMSN were in the nanorange (144.1 ± 0.70 nm), had negative Zeta potential (-15.7 ± 0.46 mV) and had a nearly spherical morphology. <i>In vitro</i>, drug release investigations showed a controlled pH-dependent release profile under mild acidic conditions that could enhance the targeted chemotherapeutic response against cancer in mild acidic environments. The obtained LIG-ROS-BMSN nano valve achieved significantly lower IC₅₀ values of (1.70 ± 0.01 μg/mL and 3.25 ± 0.14 μg/mL) against Hep-G2 and NCI-H460 cell lines as compared to ROS alone, which was (14.0 ± 0.7 μg/mL and 29.10 ± 0.25 μg/mL), respectively. The cellular morphology before and after treatment was further confirmed <i>via</i> inverted microscopy. The outcomes of the current study imply that our designed LIG-ROS-BMSN nanovalve is a potential carrier for cancer chemotherapeutics.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"541-550"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071639","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}