Drug Development and Industrial Pharmacy最新文献

{"title":"Amplifying therapeutic potential through optimization of bioavailability of poorly soluble flavonols via albumin-based nanoparticles.","authors":"Shayeri Chatterjee Ganguly, Ritam Maity, Priya Manna, Avisek Sardar, Swarupananda Mukherjee, Dipanjan Karati","doi":"10.1080/03639045.2025.2490281","DOIUrl":"10.1080/03639045.2025.2490281","url":null,"abstract":"<p><strong>Objective: </strong>Flavonols have different pharmacological actions that render them highly promising therapeutic targets. However, their water solubility and bioavailability are low, which restricts their therapeutic potential. ABNPs, albumin-based nanoparticles, are potential nanocarriers that enhance flavonol solubility, stability, and targeted delivery. By utilizing ABNPs, in this work we provide a detailed overview of strategies employed to attain maximum bioavailability of poorly water-soluble flavonols. The review critically evaluates ABNP-mediated delivery's pharmacokinetic advantage, physicochemical properties, and formulation principles. We also highlight existing gaps in research, such as the need for stringent <i>in vivo</i> validity tests, standardized formulation procedures, and in-depth mechanistic understanding of flavonol-albumin interactions.</p><p><strong>Significance: </strong>Despite having potential therapeutic activities, the utilization of flavonoids in the form of medication is limited. Some recent studies have shown that flavonoids exhibit low solubility, low permeability and chemical instability, thereby limiting their bioavailability and therapeutic responses.</p><p><strong>Methods: </strong>To overcome these drawbacks, multiple novel drug delivery approaches have emerged in the pharmaceutical research.</p><p><strong>Results: </strong>These novel approaches seem to offer a viable foundation for improving the bioavailability of the flavonoids and positioning them as viable therapeutic options. Out of all the polymers implemented in enhancing the solubility and bioavailability of the flavonoids, albumin-based nanomaterials have been the most efficacious one.</p><p><strong>Conclusion: </strong>Compared to all other polymeric nano-carriers, albumin nano-carriers offer a greater scale of drug entrapment and drug loading because of their capacity for surface modification, crosslinking, conjugation, coupling, and characteristics including biodegradability and biocompatibility.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"534-545"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788079","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":"Optimizing paracetamol-ascorbic acid effervescent tablet characteristics: a quality by design approach  .","authors":"Nur Tasnim Adlina Mazdi, Nur Aisyah Mior Mat Zin, Muhammad Aiman Khairul Hisham, Shaiqah Mohd Rus, Muhammad Salahuddin Haris, Bappaditya Chatterjee","doi":"10.1080/03639045.2025.2495131","DOIUrl":"10.1080/03639045.2025.2495131","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to optimize paracetamol-ascorbic acid (PCM-AA) effervescent tablet characteristics through a Quality-by-Design (QbD) approach, investigating the effects of binder concentration, granulation time, and effervescent agents' ratio on hardness, disintegration, and dissolution of the tablets.</p><p><strong>Methods: </strong>The QbD approach was implemented by identifying the quality target product profile, critical quality attributes (CQAs), critical material attributes (CMAs), and critical process parameters for formulating PCM-AA effervescent tablets. An Ishikawa diagram identified risk factors for CQAs. A risk estimation matrix evaluated the levels of associated risks. A central composite design-based response surface methodology with 20 experimental runs, including six center points, identified key factors (binder concentration, granulation time, and effervescent agents' ratio) influencing tablet characteristics (hardness, disintegration, dissolution). The optimum formulation, determined by numerical analysis, was characterized for weight uniformity, tablet thickness and diameter, friability, and PCM and AA assay.</p><p><strong>Results: </strong>Optimized PCM (500 mg)-AA(200 mg) effervescent tablets with 2.9% PVP concentration, 15 min granulation time, and 1:1.5 (w/w) sodium bicarbonate-citric acid ratio achieved acceptable characteristics (hardness: 45 N ± 20 N, disintegration: <5 min, and both PCM and AA dissolution: <10 min). Model validation showed no significant difference (<i>p</i> > 0.05), indicating consistent results.</p><p><strong>Conclusion: </strong>The study successfully optimized the hardness, disintegration, and dissolution rate of PCM-AA effervescent tablets via the QbD approach. Granulation time affects hardness and PCM dissolution, binder concentration influences disintegration time, and the effervescent agents' ratio impacts both disintegration time and AA dissolution. This research enhances the understanding of pharmaceutical formulation processes, risk management, and optimization in effervescent tablet development.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"647-658"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962387","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":"Q1 and Q2 selection, Q3, IVRT, IVPT, pharmacokinetic and pharmacodynamic evaluation of topical generic product.","authors":"Feng Jie, Om Shelke, Zhu Yijie, Chen Yulan, Liu Yongbo","doi":"10.1080/03639045.2025.2486487","DOIUrl":"10.1080/03639045.2025.2486487","url":null,"abstract":"<p><strong>Objective: </strong>To establish a detailed step-by-step example for the topical development of generic products.</p><p><strong>Significance: </strong>Topical semisolids are complex products requiring extensive research for bioequivalence by establishing Q1/Q2/Q3.</p><p><strong>Methods: </strong>The detailed process establishes Q1/Q2 selection and Q3 evaluation of the innovator and proposed formulation. The proposed generic product along with the innovator formulation has been evaluated for physicochemical properties. Once the Q3 structure is matched with innovator formulation, the invitro release and in-vitro permeation study have been conducted to move forward for the bioequivalence study. Pharmacokinetic and pharmacodynamic studies were employed for bioequivalence with an innovator in humans.</p><p><strong>Results: </strong>Selection of Q1 and Q2 establish the formulation composition through literature search and reverse engineering. The test and reference products are pharmaceutically equivalent through Q3 characterization, IVRT, and IVPT. In the PK study, test and reference samples were compared for Cmax, T_max, and t_1/2 and found bioequivalent. The PD study was performed in pilot and pivotal study to establish dose duration response relationship and bioequivalence respectively without adverse events. A crucial study has exhibited that reference and test formulations are bioequivalent with a 90% confidence interval and results in 84.67%-101.09%.</p><p><strong>Conclusion: </strong>The Cutivate^® cream 0.05%, and proposed generic product Fluticasone Propionate cream 0.05% formulations are bioequivalent and have a favorable safety profile.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"555-565"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771613","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":"Stearyl amine coated liposome of rotigotine alleviates cognitive deficit in Parkinson's disease induced mice model: modulation of oxidative stress, and motor coordination.","authors":"Kartik Bhairu Khot, Jobin Jose, Gopika Gopan, D S Sandeep, Harsha Ashtekar, Prajna Shastry, Chaithra Raviraj","doi":"10.1080/03639045.2025.2494127","DOIUrl":"10.1080/03639045.2025.2494127","url":null,"abstract":"<p><strong>Objective: </strong>The study was conducted to evaluate the brain targeted delivery of cationic liposomes of rotigotine <i>via</i> nasal route, addressing the limitations in brain penetration for Parkinson's disease intervention.</p><p><strong>Methods: </strong>Cationic liposomes were fabricated and optimized using a Box-Behnken design to improve the excipient composition for effective intranasal delivery. The optimized liposome, LR12, was surface modified with stearylamine at three concentrations to confer a cationic charge. The final formulation, RTG-LP3, was evaluated for physicochemical parameters, including size, entrapment efficiency, and zeta potential. A morphological study was performed within the 100-200 nm size range. The cytotoxicity of RTG-LP3 was determined in SH-SY5Y cell lines, whereas pharmacodynamic studies were evaluated in C57BL/6 mice following nasal administration.</p><p><strong>Results: </strong>The formulation RTG-LP3 exhibited a minimal vesicle size of 162 ± 2.94 nm, a high entrapment efficiency of 86.53 ± 0.33%, and a positive zeta potential of +19.8 ± 2.45 mV. Morphological investigation indicated spherical shape of liposomes in the size range of 100-200 nm. Cytotoxicity study showed fivefold safety margin for RTG-LP3 when compared with rotigotine. Pharmacodynamic assessments in PD-induced C57BL6 mice showed increased motor coordination and antioxidant benefits following nasal treatment. Histological study of brain regions treated with RTG-LP3 demonstrated improved neuronal architecture, indicating reduced neurodegeneration and improved disease condition.</p><p><strong>Conclusion: </strong>The cationic liposome RTG-LP3 demonstrated effective delivery of liposomes with superior therapeutic effects in treating PD <i>via</i> nasal route. These findings highlight the potential of cationic liposomes as a viable method for improving brain penetration and neuroprotection in PD therapy.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"606-621"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997036","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":"Correction.","authors":"","doi":"10.1080/03639045.2025.2496017","DOIUrl":"10.1080/03639045.2025.2496017","url":null,"abstract":"","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"659"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968729","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":"A QbD approach for optimizing the lyophilization parameters of cyclophosphamide monohydrate.","authors":"Shaik Riyaz Ahammad, Damodharan Narayanasamy","doi":"10.1080/03639045.2025.2487615","DOIUrl":"10.1080/03639045.2025.2487615","url":null,"abstract":"<p><strong>Purpose: </strong>Cyclophosphamide, an active pharmaceutical ingredient (API), is accessible in monohydrate form and esteemed for its remarkable stability. Maintaining this monohydrate form post-lyophilization is essential for product stability. This research aims to optimize essential lyophilization parameters for an effective and robust lyophilization cycle using a Quality by Design (QbD) methodology.</p><p><strong>Methods: </strong>Initially, thermal analysis is performed to evaluate the thermal qualities of the product. The research defines critical process parameters (CPPs) and important quality attributes (CQAs), employing a systematic Quality by Design (QbD) methodology to establish the design space in accordance with the required Quality Target Product Profile (QTPP). The lyophilization parameters being examined are primary drying temperature, primary drying duration, and primary drying vacuum. Meticulous analysis of the results identifies an optimum formulation.</p><p><strong>Results: </strong>The test product successfully preserves water content between 6 and 7%, hence confirming the existence of the monohydrate form, as verified by X-ray diffraction (XRD) examination. Furthermore, the product demonstrates minimal concentrations of TBA and ACN, maintains an intact cake structure, and achieves a rapid reconstitution time of less than 30 s.</p><p><strong>Conclusion: </strong>The implementation of Quality by Design (QbD) concepts to enhance lyophilization parameters offers significant insights for developing generic pharmaceutical lyophilization formulations. Ultimately, a reliable freeze-drying technique is developed and then requires validation on industrial-scale lyophilizers for commercial applications.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"566-576"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751627","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":"Effect of PVP and HPMC on production of indomethacin amorphous nanoparticles: experiments and molecular dynamics simulations.","authors":"Wenhui Zhou, Mengmeng Han, Haosen Zhang, Tianwei Zhang, Haiyun Tian, Tingting Yang, Tao Liu","doi":"10.1080/03639045.2025.2495136","DOIUrl":"10.1080/03639045.2025.2495136","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the effect of molecular interactions between drug and polymers on preparation of nanoamorphous indomethacin (IND) through milling of solid dispersions (SDs).</p><p><strong>Significance: </strong>The polymer selection (molecular interaction) emerged as a critical factor in the dynamic milling process for achieving nanoamorphous drug.</p><p><strong>Methods: </strong>Polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) were selected as models. Amorphous dispersions were used to prepare nanoamorphous drugs by applying wet milling. Molecular simulations were employed to elucidate the molecular mechanisms of drug-polymer miscibility, interaction energy, and molecular migration.</p><p><strong>Results: </strong>Both PVP and HPMC related SDs could be nanosized after milling. The rate of size reduction might be related to the solid state of the dispersions. The combination of amorphous PVP SDs with reduced particle size significantly improved the dissolution rate of IND. However, HPMC-based samples exhibited recrystallization during milling. Molecular simulation indicated that PVP formed strong molecular interaction with the drug to maintain the amorphous form, which contributed to avoid recrystallization induced by the external milling forces. The radial distribution function of hydrated IND/HPMC amorphous cells demonstrated the absence of hydrogen bonding interactions between IND and HPMC.</p><p><strong>Conclusion: </strong>PVP contributed to maintain the amorphous state during the milling process, which resulted from the higher molecular binding energy compared to HPMC. Controlled milling of amorphous SD with optimized polymer selection could simultaneously achieve nanoamorphous particle and enhanced dissolution rate.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"622-633"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985696","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":"Thermosensitive chitosan hydrogel loaded cetuximab: a novel approach for parenteral controlled delivery.","authors":"Ahmed A H Abdellatif, Abdullah Aljutayli, Ahmed M Mohammed","doi":"10.1080/03639045.2025.2494126","DOIUrl":"10.1080/03639045.2025.2494126","url":null,"abstract":"<p><strong>Objective: </strong>The controlled release method improves the stability of cetuximab (CTX), which is typically impacted by the environmental variables present in regular formulations.</p><p><strong>Significant: </strong>It is possible to preserve the effectiveness of CTX by encapsulating it in a chitosan hydrogel to reach the target site <i>via</i> direct injection easily.</p><p><strong>Method: </strong>CTX was loaded into the thermosensitive polymer-based hydrogel, namely chitosan (CH) with the aid of a crosslinking β-glycerophosphate (β-GP) alone or in combination with Pluronic F127 (<math><mtext>Pl F</mtext><mn>127</mn></math>). The formulated hydrogels were subjected to different types of characterizations, such as stability and rheological studies. Furthermore, they were tested for their antiproliferative activities against HEPG2 (hepatic cancer cell lines).</p><p><strong>Results: </strong>Hydrogels had a homogeneous preparation, were transparent, and showed no signs of aggregation. Moreover, CH/β-GP gel type recorded a lower viscosity in comparison to the other hydrogel type <math><mtext>CH</mtext><mo>/</mo><mi>β</mi><mo>-</mo><mtext>GP</mtext><mo>/</mo><mtext>Pl F</mtext><mn>127</mn></math> system of (110.3 ± 5.2, and 148.4 ± 4.4 Cp, respectively). The conducted pharmacokinetic studies demonstrated a continued increase in rabbits' plasma throughout the first four days (<i>T</i>_max) with <i>C</i>_max of 3.663 μg/mL which also showed a decline below the detected limit after 15 days. Nevertheless, the formulated CH-based hydrogel showed a sustained release with a longer value of MRT of more than 9 days with an estimated AUC_0-t of 41.917 μg/L/day.</p><p><strong>Conclusion: </strong>The medicated CH/β-GP hydrogel formula demonstrated superior targeting-controlled efficiency compared to free CTX.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"597-605"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986352","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":"The use of nanomedicines in the healthcare systems: a policy brief.","authors":"Somayeh Vandghanooni, Mehdi Jaymand, Morteza Eskandani","doi":"10.1080/03639045.2025.2489594","DOIUrl":"10.1080/03639045.2025.2489594","url":null,"abstract":"<p><strong>Objective: </strong>Nanomedicine is the application of nanotechnology to medicine and, therefore, a potentially transformative approach to healthcare. This new and interdisciplinary field has three main applications in diagnostics, controlled/targeted drug delivery, and regenerative medicine. Nanomedicine has great potential to change human health by advancing diagnosis, prevention and treatment for a wide variety of diseases, including cancer, cardiovascular conditions, and neurological disorders. Despite the overwhelming potential, there are some issues impeding the complete integration of nanomedicines into healthcare systems.</p><p><strong>Significance: </strong>This policy brief addresses such critical issues to inform and guide decision-making on effectively deploying nanomedicine to improve patient outcomes and advance important public health initiatives. In addition, some prospects were also presented for the future. It discusses the current barriers to their wide application, particularly regarding regulatory hurdles and the production of robust clinical evidence.</p><p><strong>Key findings: </strong>These brand-new nanosystems have some serious drawbacks in regard to safety, efficacy, and regulatory compliance, not to mention public acceptance. Nanomaterials can be so complex that their manufacturing processes become complex, which may potentially bring into question long-term effects on human health and the environment.</p><p><strong>Conclusions: </strong>This policy brief identifies key considerations for policymakers and stakeholders, highlighting the requirement for integration among researchers, clinicians, and regulatory bodies. To facilitate the safe and successful integration of nanomedicines into patient care, continued collaboration are imperative. Priority in the future should be given to developing comprehensive regulatory frameworks, raising public awareness, and promoting interdisciplinary research to resolve existing challenges and unlock the potential of nanomedicines in the healthcare sector.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"523-533"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788126","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":"Stability indicating HPTLC - densitometric method for estimation of vonoprazan fumarate.","authors":"Mitalben S Parmar, Dimal A Shah, Usmangani K Chhalotiya","doi":"10.1080/03639045.2025.2492192","DOIUrl":"10.1080/03639045.2025.2492192","url":null,"abstract":"<p><strong>Objectives: </strong>High performance thin layer chromatography method was developed and validated for analysis of vonoprazan fumarate. An Alkaline forced degradation kinetic study was performed to find out probable rate of degradation of vonoprazan fumarate.</p><p><strong>Material and methods: </strong>Aluminum packed TLC plates precoated with silica gel 60 F 254 were used as stationary phase and Methanol: Toluene: triethylamine (6: 4: 0.1 v/v/v) was used as mobile phase. The detection was carried out at 267 nm wavelength as absorbance mode. HPTLC/MS analysis study was performed to detect alkaline degradant.</p><p><strong>Results: </strong>A compact band (R_f value of 0.43 ± 0.1) was obtained for vonoprazan fumarate. Regression analysis shows a good linear relationship (R² = 0.9996) between peak area and concentration in the range 200-1200 ng/band. The accuracy determined by standard addition method for vonoprazan fumarate and percentage recovery was found to be 99.72% - 101.74%. Forced degradation stability study was performed under different stress conditions including hydrolytic, oxidative, thermal and photolytic. Degradation was observed under alkaline condition and it was found to follow first order degradation kinetic. The possible structure of base degradants was also determined using HPTLC-MS analysis. The method was successfully applied for the estimation of drug in synthetic mixture.</p><p><strong>Conclusion: </strong>A New, Simple, precise and accurate method has been developed and validated for the quantification of vonoprazan fumarate. Forced degradation studies were performed. The method can be used for quality control and stability sample evaluation of vonoprazan fumarate.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":" ","pages":"546-554"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991485","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}