Pharmaceutical Development and Technology最新文献

{"title":"Formation and stabilization mechanism of Ginsenoside Rg3 inclusion complexes based on molecular simulation.","authors":"Shili Pan, Wei Shen, Xuehui Ding, Jingying Li, Jiahui Xu, Jixin Li, Ye Qiu, Wei Xu","doi":"10.1080/10837450.2024.2448618","DOIUrl":"10.1080/10837450.2024.2448618","url":null,"abstract":"<p><p>The formation of inclusion complexes between Ginsenoside Rg3 and cyclodextrins represents a promising strategy to enhance the solubility of G-Rg3. Nevertheless, the molecular mechanisms underlying the interaction between G-Rg3 and cyclodextrins have yet to be fully elucidated. In this study, we employed a combination of molecular simulation and experimental methodologies to identify the most effective solubilizing carriers among G-Rg3, β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), and 2,6-dimethyl-β-cyclodextrin (DM-β-CD). The inclusion complexes formed with HP-β-CD demonstrates superior stability and water solubility compared to those formed with β-CD and DM-β-CD. The preparation process for the inclusion complexes of G-Rg3 and HP-β-CD was optimized through an orthogonal testing approach. The optimal conditions were determined to be a mass ratio of G-Rg3 to HP-β-CD of 1:125, an inclusion time of 2 h, and an inclusion temperature of 30 °C. The formation of the inclusion complexes was confirmed using DSC, Fourier Transform Infrared FTIR, and XRD techniques. <i>In vitro</i> solubility tests indicated that the solubility of the G-Rg3 inclusion complexes was 2.9 times greater than that of G-Rg3. Molecular dynamics (MD) simulations provided insights into the mechanisms that stabilize the inclusion complexes and enhance their water solubility. The primary interaction force between G-Rg3 and HP-β-CD was identified as the van der Waals force.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"79-89"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915389","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":"Drug-silica-cellulose ternary matrix for the oral delivery of Cyclosporine A: <i>in vitro</i> and <i>in vivo</i> evaluation.","authors":"Pinal Chaudhari, Vivek M Ghate, Arun K Kodoth, Sumit Birangal, Shaila A Lewis","doi":"10.1080/10837450.2024.2448625","DOIUrl":"10.1080/10837450.2024.2448625","url":null,"abstract":"<p><strong>Purpose: </strong>Supersaturated formulations have been widely explored for improving the oral bioavailability of drugs by using mesoporous silica (MS) to generate supersaturation <i>via</i> molecular adsorption; however, this is followed by precipitation. Several precipitation inhibitors (PI) have been explored to prevent precipitation and maintain the drug in solution for a longer period. However, the combined approach of MS and PIs, the impact of MS and Silica, and the loading of high-molecular-weight neutral molecules such as Cyclosporine A (CsA) have not yet been explored. The present study aimed to explore the impact of MS and a hydroxypropyl methylcellulose (HPMC) matrix on the supersaturation and bioavailability of the neutral drug CsA.</p><p><strong>Methods: </strong>A CsA-loaded mesoporous silica/HPMC ternary matrix and CsA-HPMC and CsA-MS controls were prepared, and physicochemical characterization was carried out. The ternary matrix and controls were investigated for the Non-sink Mini FaSSIF dissolution and biorelevant transfer studies. Furthermore, drug release modeling was performed using DDSolver, and pharmacokinetic studies were performed to assess the impact on oral bioavailability compared with the marketed formulation.</p><p><strong>Results: </strong>The study suggested that the co-loaded CsA, HPMC, and MS demonstrated higher supersaturation than CsA-loaded silica and CsA-HPMC controls. A significant improvement in FaSSIF single medium (2-fold) and biorelevant transfer (3.37-fold) increase in the dissolution profile was observed for the co-loaded CsA-MS-HPMC samples. The <i>in vitro</i> dissolution profile was corroborated by pharmacokinetic studies, which showed a 1.19-fold higher oral bioavailability of CsA-MS-HPMC compared to that of CsA-MS and CsA-HPMC.</p><p><strong>Conclusion: </strong>The pharmacokinetics indicated that CsA-MS-HPMC co-loaded samples demonstrated supersaturation and improved bioavailability compared with the physical mixture.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"114-125"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927378","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":"Thermoresponsive biomaterial system of irinotecan and curcumin for the treatment of colorectal cancer: <i>in-vitro</i> and <i>in-vivo</i> investigations.","authors":"Aleena Maryiam, Sibgha Batool, Zakir Ali, Fatima Zahid, Ali H Alamri, Taha Alqahtani, Adel Al Fatease, Ahmed A Lahiq, Muhammad Waseem Khan, Fakhar Ud Din","doi":"10.1080/10837450.2024.2448334","DOIUrl":"10.1080/10837450.2024.2448334","url":null,"abstract":"<p><p>This study aims to develop a thermoresponsive biomaterial system of irinotecan (IRT) and curcumin (CUR) nano-transferosomal gel (IRT-CUR-NTG) for targeting colorectal cancer (CRC). The IRT-CUR-NTs were statistically optimized and loaded into poloxamer-based thermosensitive gel. Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) of the IRT-CUR-NTs were performed, whereas pH, gelation time, gelation temperature, gel and mucoadhesive strength of the IRT-CUR-NTG were investigated. <i>In-vitro</i> release and anticancer analyses were explored using HT29 cells. Additionally, <i>in-vivo</i> pharmacokinetics study was investigated followed by histopathological examination and <i>in-vivo</i> anticancer analysis. The PS, PDI, ZP, %EE of IRT and %EE of CUR were found to be 136.15 nm, 0.143, -15.5 mV, 95.05% and 85.12%, respectively. IRT-CUR-NTs exhibited spherical shape with no chemical interactions among the constituents. Similarly, IRT-CUR-NTG was homogenous gel suitable for rectal administration. IRT-CUR-NTG manifested prolonged release profiles of IRT and CUR. Moreover, a significantly enhanced (4-fold) bioavailability and no toxicity of IRT-CUR-NTG was observed when compared with conventional gel. IRT-CUR-NTs were found to be more effective against HT29 cell lines. <i>In-vivo</i> antitumor analysis demonstrated significantly reduced tumor volume and tumor mass after treatment with IRT-CUT-NTG, indicating improved antitumor effect. It can be concluded that IRT-CUR-NTG is suitable biomaterial system for colorectal cancer.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"37-56"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896415","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":"Thymoquinone loaded lipid nanocapsule dispersion: two methods of preparation, characterization and <i>in vitro</i> evaluations for oral administration.","authors":"Mouna Selmi, Amine Trabelsi, Nolwenn Lautram, David Dallerac, Guillaume Lefebvre, Leila Chekir Ghedira, Emilie Roger","doi":"10.1080/10837450.2024.2448616","DOIUrl":"10.1080/10837450.2024.2448616","url":null,"abstract":"<p><p>This work explores two methods to encapsulate Thymoquinone (TQ) into lipid nanocapsules (LNCs) for oral administration. TQ was added during the phase inversion temperature method (TQ-LNCs-1) or to unload LNCs dispersion (TQ-LNCs-2). LNCs were evaluated for mean diameter, polydispersity index (PDI), ζ-potential, drug loading (DL), drop tensiometer, storage stability, <i>in vitro</i> stability in simulated gastrointestinal fluids (SGIF), and intestinal permeability across Caco-2 cells. TQ-LNCs-1 and TQ-LNCs-2 produced NPs (58.3 ± 3.7 nm and 61.5 ± 3.5 nm, respectively), with a DL of 8.7 ± 0.2 and 7.7 ± 0.6 mg/mL of suspension, respectively. For both, less than 14% of TQ was released in SGIF, and a minor increase in TQ intestinal permeability with LNCs compared to free TQ was observed. TQ-LNCs represented a promising formulation for oral delivery of TQ. Encapsulation of TQ by adding it at LNCs dispersion can be extended for further drugs.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"69-78"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922583","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":"Pharmaceutical excipients in pediatric and geriatric drug formulations: safety, efficacy, and regulatory perspectives.","authors":"Tansel Comoglu, Emine Dilek Ozyilmaz","doi":"10.1080/10837450.2024.2441181","DOIUrl":"10.1080/10837450.2024.2441181","url":null,"abstract":"<p><p>Pharmaceutical excipients are indispensable components of drug formulations, playing critical roles in enhancing stability, improving bioavailability, and ensuring patient compliance. In pediatric and geriatric populations, the selection of these excipients becomes even more crucial due to their unique physiological and pharmacokinetic profiles, as well as age-specific formulation requirements. This review examines the functions, safety considerations, and potential adverse effects of excipients in these vulnerable groups. It addresses the challenges of drug formulation for neonates, infants, and elderly patients, including immature enzyme systems, polypharmacy, and swallowing difficulties. The impact of excipient-excipient and excipient-active pharmaceutical ingredient (API) interactions on drug stability, efficacy, and safety is also highlighted. For instance, the effects of polyethylene glycol (PEG) in patients with impaired renal function and destabilizing interactions between surfactants and protein-based APIs are analyzed. Additionally, current guidelines and safety requirements from regulatory bodies such as the FDA, EMA, and ICH are reviewed. This paper emphasizes the importance of carefully selecting excipients that balance functionality and safety to ensure therapeutic efficacy while minimizing risks for pediatric and geriatric patients. Future directions in excipient development and formulation strategies are also discussed to improve treatment outcomes for these populations.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807677","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":"Indomethacin-encapsulated PLGA nanoparticles improve therapeutic efficacy by increasing apoptosis and reducing motility in glioblastoma cells.","authors":"Ferhat Bostancı, Aslıhan Şengelen, Yunus Aksüt, Eren Yıldırım, İrem Öğütcü, Oğuz Yücel, Serkan Emik, Gülten Gürdağ, Murat Pekmez","doi":"10.1080/10837450.2024.2448333","DOIUrl":"10.1080/10837450.2024.2448333","url":null,"abstract":"<p><p>Glioblastoma, with a low survival rate, is an aggressive and difficult-to-treat lethal type of brain cancer. Indomethacin (IND), a non-steroidal anti-inflammatory drug, has antitumoral activity in many cancers, including gliomas. However, its poor aqueous solubility is a critical issue. Nanomaterials are crucial tools for overcoming solubility problems and facilitating drug delivery. Herein, a polymeric nanoparticle system, poly(lactic-co-glycolic acid) (PLGA) was used to encapsulate IND. Although PLGA is an FDA-approved copolymer for drug delivery, no trials with IND-loaded PLGA-NPs have been conducted to treat brain tumors. Encapsulation success was revealed by DLS, zeta potential, TEM, and FTIR analysis; IND/PLGA-NPs had nanoscale particle size (160.6 nm), narrow size distribution (0.230, PDI), and good stability (-23.9 mV). Fluorescence imaging showed that PLGA-NPs can penetrate U-87MG cells. Short-term/one-hour treatment with bound-IND increased the free-IND effect in gliomas by ⁓10 times/48h and 12.39 times/72h. Even against long-term exposure to IND, IND/PLGA-NP treatment revealed a highly marked result; the IC₅₀ value of bound-IND (treatment-time:1h, analysis at 48h) was ∼200µM, IC₅₀ value of free-IND (treatment-time:48h) was ∼390µM. Furthermore, IND/PLGA-NPs' anticancer activity (100 µM of IND/1h, analysis at 48h) was also supported by induced apoptosis and reduced migration/colony formation in glioma cells. All evidence suggests that IND/PLGA-NPs may be a potentially promising agent for treating gliomas.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"25-36"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922527","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 characterization of poly(ethylene glycol)-<i>b</i>-poly(<i>tert</i>-butyl methacrylate) micelles as potential nanocarriers for donepezil.","authors":"Gizem İğdeli, Laura Fritzen, Claus U Pietrzik, Binnur Aydogan Temel","doi":"10.1080/10837450.2024.2423833","DOIUrl":"10.1080/10837450.2024.2423833","url":null,"abstract":"<p><p>Polymeric micelles were prepared for the delivery of donepezil, a leading Alzheimer's disease drug, to enhance its transport across the blood-brain barrier (BBB). Poly(ethylene glycol)-<i>b</i>-poly(<i>tert</i>-butyl methacrylate) amphiphilic block copolymers were synthesized <i>via</i> reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Empty and donepezil loaded polymer micelles were formed using the dialysis method and characterized by dynamic light scattering and transmission electron microscopy. Drug loading efficiency and release behavior were monitored using UV/Vis spectroscopy, and cytotoxicity was evaluated <i>via</i> colorimetric tests and impedance measurements. Additionally, the permeability of the nanocarriers across an <i>in vitro</i> BBB culture model was assessed. Drug-loaded micelles demonstrated similar permeability to free donepezil but offered sustained release and improved stability. This micellar delivery system holds significant potential for improving therapeutic outcomes in Alzheimer's treatment by enhancing donepezil's delivery across the BBB. Improved BBB permeability and sustained drug release could lead to more effective concentration of the drug in the brain, potentially reducing peripheral cholinergic side effects, such as nausea and vomiting, often observed with traditional donepezil administration. This could result in better patient compliance and improved cognitive outcomes, making this nanocarrier system a promising alternative for Alzheimer's therapy.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1111-1120"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546707","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":"Applications of therapeutic deep eutectic solvents (THEDESs) as antimicrobial and anticancer agents.","authors":"Hala Bakr El-Nassan","doi":"10.1080/10837450.2024.2421786","DOIUrl":"10.1080/10837450.2024.2421786","url":null,"abstract":"<p><p>Deep eutectic solvents (DESs) are green alternatives to ionic liquids with wide applications in organic synthesis and catalysis. DESs are characterized by being easily prepared, biodegradable, nontoxic, and noninflammable. When one or more of the DES components is active pharmaceutical ingredient (API), the eutectic mixtures are named as therapeutic deep eutectic solvents (THEDESs). THEDESs are prepared in order to improve the solubility and/or the permeability of the APIs. This review presents a brief summary of the most important THEDESs reported to date having antimicrobial and/or anticancer activities. The challenges and limitations of THEDES preparation were also discussed. The work presented here indicated the importance of THEDES as a promising drug delivery system that can overcome the bioavailability problems while retaining or enhancing the biological activity of its components.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1084-1092"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505801","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 evaluation of ibrutinib-loaded glycyrrhizic acid conjugated ovalbumin nanoparticles and ibrutinib-glycyrrhizic acid complex for improved oral bioavailability.","authors":"Prateeksha Prakash Kamath, Pragathi Devanand Bangera, Divya Dhatri Kara, Rajeshwari Roychowdhury, Vamshi Krishna Tippavajhala, Mahalaxmi Rathnanand","doi":"10.1080/10837450.2024.2436190","DOIUrl":"10.1080/10837450.2024.2436190","url":null,"abstract":"<p><p>The study aimed at enhancing the oral bioavailability of the BCS class 2 drug Ibrutinib (IBR), which exhibits low solubility (0.002 mg/mL) and high permeability (3.9% oral bioavailability). This was achieved through the formulation and evaluation of Ibrutinib-loaded Glycyrrhizic acid conjugated egg ovalbumin nanoparticles (IBR-GA-EA NPs) and Ibrutinib-Glycyrrhizic acid complex (IBR-GA-COMP). The formulation of Ibrutinib-Glycyrrhizic acid complex aimed to enhance the oral bioavailability of Ibrutinib. Lyophilized Ibrutinib-Glycyrrhizic acid complex was prepared and characterized through various studies including DSC, FTIR, <i>in vitro</i> release, and <i>in vivo</i> pharmacokinetics studies. DSC and FTIR confirmed successful formulation development. The nanoparticles exhibited spherical morphology with favourable characteristics: particle size of 194.10 nm, PDI of 0.22, and zeta potential of -33.96 mV. Encapsulation efficiency was 82.88%. <i>In vitro</i> release study displayed major improvement in drug release pattern compared to the free drug suspension. <i>In vivo</i> pharmacokinetic studies demonstrated 3.21-fold and 3.41-fold increase in the oral bioavailability of IBR-GA-EA NPs and IBR-GA-COMP, respectively, compared to IBR suspension alone. The formulated IBR-GA-EA NPs and IBR-GA-COMP are promising drug delivery methods as they successfully improve the solubility and oral bioavailability of Ibrutinib.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1185-1198"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789634","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":"Mechanistic characterization of fast dissolving PVP-I powder with multipolymer approaches and investigation on their molecular interaction.","authors":"Maytawee Wutthichokmongkhonkul, Rutthapol Sritharadol, Teerapol Srichana","doi":"10.1080/10837450.2024.2428772","DOIUrl":"10.1080/10837450.2024.2428772","url":null,"abstract":"<p><p>Povidone-iodine (PVP-I) is widely used as an antiseptic in medical applications. However, its effectiveness is limited by certain drawbacks, such as low solubility in water and high volatility. Therefore, a formulation of a stable solid PVP-I is desirable. In this study, complexes of molecular PVP-I with polyethylene glycol-polyvinyl alcohol copolymer (PEG-PVA copolymer) were considered water-soluble iodophors. Two different methods were used to prepare the solids: physical mixtures and kneading. The physical characteristics of the obtained solids were evaluated using several spectroscopic methods. The presence of iodine was confirmed by a potentiometric titration and antimicrobial activity was tested. The results showed that the PEG-PVA copolymer interacted with povidone primarily through hydrogen bonding between the hydroxyl part of the PEG-PVA copolymer and the amide part of povidone with an estimated binding energy of 3.2 kcal/mol. The amide groups polarity in povidone made them more likely to form hydrogen bonds with the PEG-PVA copolymer. Also, the protonated pyrrolidone bonded to the triiodide anions by intermolecular hydrogen bonds, which increased PVP-I solubility in water. The kneading method provided a faster dissolution rate than physical mixing and pure PVP-I. The iodine contents were within an acceptable range (10-12%), and the antimicrobial activity proved effective against <i>Staphylococcus aureus</i>, <i>Staphylococcus epidermidis</i>, and <i>Streptococcus mutans</i>.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1162-1174"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626013","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}