Pharmaceutics最新文献

{"title":"T14diLys/DOPE Liposomes: An Innovative Option for siRNA-Based Gene Knockdown?","authors":"Sophie Meinhard, Frank Erdmann, Henrike Lucas, Maria Krabbes, Stephanie Krüger, Christian Wölk, Karsten Mäder","doi":"10.3390/pharmaceutics17010025","DOIUrl":"10.3390/pharmaceutics17010025","url":null,"abstract":"<p><strong>Background/objectives: </strong>Bringing small interfering RNA (siRNA) into the cell cytosol to achieve specific gene silencing is an attractive but also very challenging option for improved therapies. The first step for successful siRNA delivery is the complexation with a permanent cationic or ionizable compound. This protects the negatively charged siRNA and enables transfection through the cell membrane. The current study explores the performance of the innovative, ionizable lipid 2-Tetradecylhexadecanoic acid-(2-bis{[2-(2,6-diamino-1-oxohexyl)amino]ethyl}aminoethyl)-amide (T14diLys), in combination with 1,2-dioleoyl-<i>sn</i>-glycero-3-phosphoethanolamine (DOPE), for siRNA delivery and the impact of the production method (sonication vs. extrusion) on the particle properties.</p><p><strong>Methods: </strong>Liposomes were produced either with sonication or extrusion and characterized. The extruded liposomes were combined with siRNA at different N/P ratios and investigated in terms of size zeta potential, encapsulation efficiency, lipoplex stability against RNase A, and knockdown efficiency using enhanced green fluorescent protein (eGFP)-marked colon adenocarcinoma cells.</p><p><strong>Results: </strong>The liposomes prepared by extrusion were smaller and had a narrower size distribution than the sonicated ones. The combination of siRNA and liposomes at a nitrogen-to-phosphate (N/P) ratio of 5 had optimal particle properties, high encapsulation efficiency, and lipoplex stability. Gene knockdown tests confirmed this assumption.</p><p><strong>Conclusions: </strong>Liposomes produced with extrusion were more reproducible and provided enhanced particle properties. The physicochemical characterization and in vitro experiments showed that an N/P ratio of 5 was the most promising ratio for siRNA delivery.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-Threonine-Derived Biodegradable Polyurethane Nanoparticles for Sustained Carboplatin Release.","authors":"Seoeun Oh, Soo-Yong Park, Hyung Il Seo, Ildoo Chung","doi":"10.3390/pharmaceutics17010028","DOIUrl":"10.3390/pharmaceutics17010028","url":null,"abstract":"<p><p><b>Background and objectives:</b> The use of polymeric nanoparticles (NPs) in drug delivery systems offers the advantages of enhancing drug efficacy and minimizing side effects; <b>Methods:</b> In this study, L-threonine polyurethane (LTPU) NPs have been fabricated by water-in-oil-in-water emulsion and solvent evaporation using biodegradable and biocompatible LTPU. This polymer was pre-synthesized through the use of an amino acid-based chain extender, desaminotyrosyl L-threonine hexyl ester (DLTHE), where urethane bonds are formed by poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) triblock copolymer and 1,6-hexamethylene diisocyanate (HDI). LTPU is designed to be degraded by hydrolysis and enzymatic activity due to the presence of ester bonds and peptide bonds within the polymer backbone. LTPU NPs were fabricated by water-in-oil-in-water double emulsion solvent evaporation methods; <b>Results:</b> The polymerization of LTPU was confirmed by ¹H-NMR, ¹³C-NMR, and FT-IR spectroscopies. The molecular weights and polydispersity, determined with GPC, were 28,800 g/mol and 1.46, respectively. The morphology and size of NPs, characterized by DLS, FE-SEM, TEM, and confocal microscopy, showed smooth and spherical particles with diameters less than 200 nm; <b>Conclusions:</b> In addition, the drug loading, encapsulation efficiency, and drug release profiles, using UV-Vis spectroscopy, showed the highest encapsulation efficiency with 2.5% carboplatin and sustained release profile.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Novel Oral Delivery Systems Using Additive Manufacturing Technologies to Overcome Biopharmaceutical Challenges for Future Targeted Drug Delivery.","authors":"Micol Cirilli, Julius Krause, Andrea Gazzaniga, Werner Weitschies, Matteo Cerea, Christoph Rosenbaum","doi":"10.3390/pharmaceutics17010029","DOIUrl":"10.3390/pharmaceutics17010029","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The development of targeted drug delivery systems for active pharmaceutical ingredients with narrow absorption windows is crucial for improving their bioavailability. This study proposes a novel 3D-printed expandable drug delivery system designed to precisely administer drugs to the upper small intestine, where absorption is most efficient. The aim was to design, prototype, and evaluate the system's functionality for organ retention and targeted drug release. <b>Methods:</b> The system was created using 3D printing technologies, specifically FDM and SLA, with materials such as PLA and HPMC. The device was composed of matrices and springs, with different spring geometries (diameter, coil number, and cross-sectional shape) being tested for strength and flexibility. A gastro-resistant string was used to maintain the device in a compact configuration until it reached the neutral pH environment of the small intestine, where the string dissolved. The mechanical performance of the springs was evaluated using a texture analyzer, and the ability of the system to expand upon pH change was tested in simulated gastrointestinal conditions. <b>Results:</b> The results demonstrated that the system remained in the space-saving configuration for two hours under acidic conditions. Upon a pH change to 6.8, the system expanded as expected, with opening times of 5.5 ± 1.2 min for smaller springs and 2.5 ± 0.3 min for larger springs. The device was able to regain its expanded state, suggesting its potential for controlled drug release in the small intestine. <b>Conclusions:</b> This prototype represents a promising approach for targeted drug delivery to the upper small intestine, offering a potential alternative for drugs with narrow absorption windows. While the results are promising, further in vivo studies are necessary to assess the system's clinical potential and mechanical stability in real gastrointestinal conditions.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review of Spironolactone Nano-Formulations for Topical Treatment of Skin Hyperandrogenic Disorders and Chronic Wounds.","authors":"Saedah Dereiah, Muhammad Usman Ghori, Barbara R Conway","doi":"10.3390/pharmaceutics17010027","DOIUrl":"10.3390/pharmaceutics17010027","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Spironolactone (SP), an aldosterone inhibitor widely used to treat androgen-dependent disorders such as acne, hirsutism, and alopecia, has demonstrated therapeutic potential in both oral and topical formulations. However, SP's low solubility and poor bioavailability in conventional formulations have driven the development of novel nanocarriers to enhance its efficacy. This review systematically examines recent advancements in SP-loaded nanocarriers, including lipid nanoparticles (LNPs), vesicular nanoparticles (VNPs), polymeric nanoparticles (PNPs), and nanofibers (NFs). <b>Methods:</b> A search strategy was developed, and the relevant literature was systematically searched using databases such as Scopus, PubMed, and Google Scholar. The review process, including screening, inclusion, and exclusion criteria, adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. <b>Results:</b> A comprehensive analysis of 13 eligible research articles, corresponding to 15 studies, highlights key aspects such as encapsulation efficiency, stability, particle size, and in vitro and in vivo efficacy. Six studies focused on lipid nanoparticles (LNPs), including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), which were found to improve SP's bioavailability and skin permeation. Another six studies investigated vesicular nanoparticles (VNPs), such as ethosomes and niosomes, demonstrating superior skin targeting and penetration capabilities. Two studies on polymeric nanoparticles (PNPs) showed effectiveness in delivering SP to hair follicles for the treatment of alopecia and acne. Additionally, one study on SP-loaded nanofibers indicated significant potential for topical rosacea therapy. <b>Conclusions:</b> SP-loaded nanocarrier systems represent promising advancements in targeted topical therapy. However, further clinical studies are required to optimize their safety, efficacy, and delivery mechanisms.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Evaluation of Neutral Sphinghomyelinase2 (nSMase2) Inhibitor Prodrugs in Mice and Dogs.","authors":"Arina Ranjit, Chae Bin Lee, Lukáš Tenora, Vijaya Saradhi Mettu, Arindom Pal, Jesse Alt, Barbara S Slusher, Rana Rais","doi":"10.3390/pharmaceutics17010020","DOIUrl":"10.3390/pharmaceutics17010020","url":null,"abstract":"<p><p><b>Background</b>: Extracellular vesicles (EVs) can carry pathological cargo, contributing to disease progression. The enzyme neutral sphingomyelinase 2 (nSMase2) plays a critical role in EV biogenesis, making it a promising therapeutic target. Our lab previously identified a potent and selective inhibitor of nSMase2, named DPTIP (IC₅₀ = 30 nM). Although promising, DPTIP exhibits poor pharmacokinetics (PKs) with a low oral bioavailability (%F < 5), and a short half-life (t_1/2 ≤ 0.5 h). To address these limitations, we previously developed DPTIP prodrugs by masking its phenolic hydroxyl group, demonstrating improved plasma exposure in mice. Recognizing that species-specific metabolic differences can influence prodrug PK, we expanded our studies to evaluate selected prodrugs in both mice and dogs. <b>Methods:</b> The scaleup of selected prodrugs was completed and two additional valine- ester based prodrugs were synthesized. Mice were dosed prodrugs via peroral route (10 mg/kg equivalent). For dog studies DPTIP was dosed via intravenous (1 mg/kg) or peroral route (2 mg/kg) and prodrugs were given peroral at a dose 2 mg/kg DPTIP equivalent. Plasma samples were collected at predetermined points and analyzed using developed LC/MS-MS methods. <b>Results:</b> In mice, several of the tested prodrugs showed similar or improved plasma exposures compared to DPTIP. However, in dog studies, the double valine ester prodrug <b>9</b>, showed significant improvement with an almost two-fold increase in DPTIP plasma exposure (AUC_0-t = 1352 vs. 701 pmol·h/mL), enhancing oral bioavailability from 8.9% to 17.3%. <b>Conclusions:</b> These findings identify prodrug <b>9</b> as a promising candidate for further evaluation and underscore the critical role of species-specific differences in prodrug PKs.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Bacterial Nanocellulose with Chemisorbed Antiseptics on Alveolar Bone Repair in Rats Undergoing Bisphosphonate Therapy.","authors":"Marcelo Matos Rocha, Valesca Sander Koth, Marcela Wiltgen Jeffman, Fernanda Gonçalves Salum, Josiane de Almeida, Karina Cesca, Karen Cherubini","doi":"10.3390/pharmaceutics17010024","DOIUrl":"10.3390/pharmaceutics17010024","url":null,"abstract":"<p><p><b>Objectives</b>: This work investigated the effect of bacterial nanocellulose (BNC) alone or with chemisorbed chlorhexidine or povidone-iodine on post-tooth extraction repair in rats undergoing bisphosphonate therapy. <b>Methods</b>: Forty Wistar rats were treated with zoledronic acid, subjected to tooth extractions and allocated into groups according to the material inserted in the post-extraction socket: (1) BNC (<i>n</i> = 10); (2) BNC/Iodine (<i>n</i> = 10); (3) BNC/Chlorhex (<i>n</i> = 10); (4) Control (<i>n</i> = 10). Maxillae were dissected and macro- and microscopically analyzed. <b>Results</b>: Oral lesion frequency on macroscopic examination did not differ between the groups, whereas it was larger in the BNC/Iodine group compared to the BNC/Chlorhex and Control. BNC/Chlorhex had significantly more connective tissue than did BNC but did not differ from the BNC/Iodine and Control. Epithelium, vital bone, non-vital bone, tooth fragment and inflammatory infiltrate did not significantly differ between the groups. BNC/Iodine showed greater CD31 immunostaining compared to BNC and the Control. Myeloperoxidase staining did not differ between the groups, and scanning electron microscopy analysis showed similar characteristics in all groups. <b>Conclusions</b>: BNC with chemisorbed povidone-iodine is associated with increased vascularization in post-extraction wounds of rats undergoing bisphosphonate therapy, whereas BNC with chemisorbed chlorhexidine improves connective tissue formation. BNC works as an effective carrier for the antiseptics tested.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Pentacyclic Triterpenoids in Non-Small Cell Lung Cancer: The Mechanisms of Action and Therapeutic Potential.","authors":"Young-Shin Lee, Ryuk Jun Kwon, Hye Sun Lee, Jae Heun Chung, Yun Seong Kim, Han-Sol Jeong, Su-Jung Park, Seung Yeon Lee, Taehwa Kim, Seong Hoon Yoon","doi":"10.3390/pharmaceutics17010022","DOIUrl":"10.3390/pharmaceutics17010022","url":null,"abstract":"<p><p>Lung cancer remains a major global health problem because of its high cancer-related mortality rate despite advances in therapeutic approaches. Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is more amenable to surgical intervention in its early stages. However, the prognosis for advanced NSCLC remains poor, owing to limited treatment options. This underscores the growing need for novel therapeutic strategies to complement existing treatments and improve patient outcomes. In recent years, pentacyclic triterpenoids, a group of natural compounds, have emerged as promising candidates for cancer therapy due to their anticancer properties. Pentacyclic triterpenoids, such as lupeol, betulinic acid, betulin, oleanolic acid, ursolic acid, glycyrrhetinic acid, glycyrrhizin, and asiatic acid, have demonstrated the ability to inhibit cell proliferation and angiogenesis, induce apoptosis, suppress metastasis, and modulate inflammatory and immune pathways in NSCLC cell line models. These compounds exert their effects by modulating important signaling pathways such as NF-κB, PI3K/Akt, and MAPK. Furthermore, advances in drug delivery technologies such as nanocarriers and targeted delivery systems have improved the bioavailability and therapeutic efficacy of triterpenoids. However, despite promising preclinical data, rigorous clinical trials are needed to verify their safety and efficacy. This review explores the role of triterpenoids in NSCLC and therapeutic potential in preclinical models, focusing on their molecular mechanisms of action.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Rehman et al. Fabrication, In Vitro and In Vivo Assessment of Eucalyptol-Loaded Nanoemulgel as a Novel Paradigm for Wound Healing. <i>Pharmaceutics</i> 2022, <i>14,</i> 1971.","authors":"Anis Rehman, Muhammad Iqbal, Barkat A Khan, Muhammad Khalid Khan, Bader Huwaimel, Sameer Alshehri, Ali H Alamri, Rami M Alzhrani, Deena M Bukhary, Awaji Y Safhi, Khaled M Hosny","doi":"10.3390/pharmaceutics17010017","DOIUrl":"10.3390/pharmaceutics17010017","url":null,"abstract":"<p><p>In the original publication, there was a mistake in Figure 4 as published [...].</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteric Coated Pellets with Lactoferrin for Oral Delivery: Improved Shelf Life of the Product.","authors":"Nika Kržišnik, Blaž Grilc, Robert Roškar","doi":"10.3390/pharmaceutics17010023","DOIUrl":"10.3390/pharmaceutics17010023","url":null,"abstract":"<p><strong>Background/objectives: </strong>Lactoferrin (Lf), a multifunctional iron-binding protein, has considerable potential for use as an active ingredient in food supplements due to its numerous positive effects on health. As Lf is prone to degradation, we aimed to develop a formulation that would ensure sufficient stability of Lf in the gastrointestinal tract and during product storage.</p><p><strong>Methods: </strong>A simple, efficient, and well-established technology that has potential for industrial production was used for the double-coating of neutral pellet cores with an Lf layer and a protective enteric coating.</p><p><strong>Results: </strong>The encapsulation efficiency was 85%, which is among the highest compared to other reported Lf formulations. The results of the dissolution tests performed indicated effective protection of Lf from gastric digestion. A comprehensive stability study showed that the stability was similar regardless of the neutral pellet core used, while a significant influence of temperature, moisture, product composition, and packaging on the stability of Lf were observed, and were therefore considered in the development of the final product. The experimentally determined shelf life is extended from 15 to almost 30 months if the product is stored in a refrigerator instead of at room temperature, which ensures the commercial applicability of the product.</p><p><strong>Conclusion: </strong>We successfully transferred a technology commonly used for small molecules to a protein-containing product, effectively protected it from the destructive effects of gastric juice, and achieved an acceptable shelf life.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Aslam et al. pH Sensitive Pluronic Acid/Agarose-Hydrogels as Controlled Drug Delivery Carriers: Design, Characterization and Toxicity Evaluation. <i>Pharmaceutics</i> 2022, <i>14</i>, 1218.","authors":"Mariam Aslam, Kashif Barkat, Nadia Shamshad Malik, Mohammed S Alqahtani, Irfan Anjum, Ikrima Khalid, Ume Ruqia Tulain, Nitasha Gohar, Hajra Zafar, Ana Cláudia Paiva-Santos, Faisal Raza","doi":"10.3390/pharmaceutics17010019","DOIUrl":"10.3390/pharmaceutics17010019","url":null,"abstract":"<p><p><b>Error in Figure</b> [...].</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}