AAPS PharmSciTech最新文献

{"title":"The Neoteric Paradigm of Biomolecule-Functionalized Albumin-Based Targeted Cancer Therapeutics","authors":"Swati Gunjkar,&nbsp;Ujala Gupta,&nbsp;Rahul Nair,&nbsp;Priti Paul,&nbsp;Mayur Aalhate,&nbsp;Srushti Mahajan,&nbsp;Indrani Maji,&nbsp;Manish K. Chourasia,&nbsp;Santosh Kumar Guru,&nbsp;Pankaj Kumar Singh","doi":"10.1208/s12249-024-02977-6","DOIUrl":"10.1208/s12249-024-02977-6","url":null,"abstract":"<div><p>Albumin is a nature-derived, versatile protein carrier, that has been explored extensively by researchers for anticancer drug delivery due to its role in enhancing drug stability, solubility, circulation time, targeting capabilities, and overall therapeutic efficacy. Albumin nanoparticles possess inherent biocompatibility, biodegradability, and passive tumor-targeting ability due to the enhanced permeability and retention effect. However, non-specific accumulation of cytotoxic agents in healthy tissues remains a challenge. In this paper, the functionalization of albumin nanoparticles using various biomolecules including antibodies, nucleic acids, proteins and peptides, vitamins, chondroitin sulfate, hyaluronic acid, and lactobionic acid have been discussed which enables specific recognition and binding to cancer cells. Furthermore, we highlight the supremacy of such a targeted approach in tumor-specific drug delivery, minimization of off-target effects, potential improvement in therapeutic efficacy, cellular internalization, reduced side effects, and better clinical outcomes. This review centers on how they have revolutionized the field of biomedical research and tuned into an excellent targeted approach. In conclusion, this review highlights in detail the role of albumin as a nanocarrier for tumor-targeted delivery using biomolecules as ligands.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581820","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":"Magnesium Stearate Fatty Acid Composition, Lubrication Performance and Tablet Properties","authors":"Natalia Veronica,&nbsp;Paul Wan Sia Heng,&nbsp;Celine Valeria Liew","doi":"10.1208/s12249-024-02980-x","DOIUrl":"10.1208/s12249-024-02980-x","url":null,"abstract":"<div><p>Magnesium stearate (MgSt) is a common tablet lubricant. As variations in MgSt properties are known to influence tablet attributes, the impact of MgSt fatty acid composition, particularly the significance of the stearate and palmitate contents, and its effects on tablet properties warrant further investigation. This study investigated the effect of MgSt with different stearate and palmitate contents but comparable physical properties (e.g. particle size, crystallinity, specific surface area and morphology) on lubrication performance and resulting tablet quality attributes, including mechanical strength, disintegratability and drug release. The influence of MgSt concentration and blending duration on the resulting tablet properties was also examined. Tablets produced using the lower stearate content MgSt had slightly higher tensile strength. The effect of MgSt stearate content was more apparent in the disintegration time and drug release, whereby MgSt of lower stearate content resulted in tablets with longer disintegration time and slower drug release. The lower stearate content also resulted in a lower lubrication performance, leading to a lesser reduction in tablet ejection force. As expected, a longer blending time of the tablet formulation blend with MgSt yielded tablets with reduced tensile strength, shorter disintegration time and slower drug release. Tablets with higher MgSt concentration showed a greater reduction in tensile strength, longer disintegration time and faster drug release. The study findings reinforced observations by other researchers and provided a better understanding of the fatty acid composition effects of MgSt on lubrication performance and the resulting tablet properties.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-02980-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vesicular Carriers for Improved Oral Anticoagulation Competence of Rivaroxaban: In Vitro and In Vivo Investigation","authors":"Samar H. Faheim,&nbsp;Gamal M. El Maghraby,&nbsp;Amal A. Sultan","doi":"10.1208/s12249-024-02962-z","DOIUrl":"10.1208/s12249-024-02962-z","url":null,"abstract":"<div><p>Rivaroxaban is an anticoagulant for avoidance and therapy of thromboembolic disorders. Unfortunately, oral bioavailability of rivaroxaban is compromised with dose increments. Accordingly, the aim was to test nano-vesicular lipid systems for improved oral anticoagulation activity of rivaroxaban. Rivaroxaban loaded niosomes, bilosomes and spanlastic formulations were prepared. The prepared systems were assessed in terms of particle size, zeta potential, transition electron microscopic features (TEM), entrapment efficiency, <i>in-vitro</i> drug release, and <i>in-vivo</i> anticoagulation performance in rats. The prepared vesicular systems exposed spherical negatively charged vesicles with mean particle size values between 136.6 nm to 387.9 nm depending on the composition. Rivaroxaban was efficiently entrapped in the vesicular systems with entrapment efficiency values ranging from 92.4% to 94.0%. Rivaroxaban underwent sustained release from the fabricated vesicular systems. The <i>in vivo</i> performance of the tested preparation revealed significant enhancement of the anticoagulation parameters. This was manifested from the prolonged clotting time, and prothrombin time. Moreover, the cut tails of the examined rats receiving the formulated nano-systems exposed a lengthy tail bleeding time compared to those receiving the un-processed rivaroxaban aqueous dispersion. In Conclusion, niosomes, bilosomes and spanlastic nano-dispersions have a potential to overwhelm the oral anticoagulation efficiency of rivaroxaban with spanlastic ranked as best.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-02962-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Investigations on the Impacts of Drugs or Excipients with Different Physicochemical and Compaction Properties on the Disintegration Behavior of Kollidon®SR-Based Binary Controlled Release Matrix Tablets","authors":"Wasfy M. Obeidat,&nbsp;Shadi F. Gharaibeh","doi":"10.1208/s12249-024-02981-w","DOIUrl":"10.1208/s12249-024-02981-w","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581779","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":"Formononetin-Loaded Self-Microemulsion Drug Delivery Systems for Improved Solubility and Oral Bioavailability: Fabrication, Characterization, In Vitro and In Vivo Evaluation","authors":"Zhihui Zou,&nbsp;Yuanyuan Xue,&nbsp;Michael Adu-Frimpong,&nbsp;ChengWei Wang,&nbsp;Zhou Jin,&nbsp;Ying Xu,&nbsp;Jiangnan Yu,&nbsp;Ximing Xu,&nbsp;Yuan Zhu","doi":"10.1208/s12249-024-02975-8","DOIUrl":"10.1208/s12249-024-02975-8","url":null,"abstract":"<div><p>This study aimed to construct a self-microemulsion drug delivery system (SMEDDS) for Formononetin (FMN) to improve its solubility and bioavailability while combining the nanocrystals (NCs) technology. The SMEDDS prescription composition was optimized with a pseudo-three-phase diagram, followed by a series of <i>in vitro</i> and <i>in vivo</i> evaluations of the selected optimal prescriptions. FMN-NCs loaded SMEDDS showed a homogeneous spherical shape in the Transmission electron microscope and the particle size was measured as (20.65 ± 1.42) nm. The <i>in vitro</i> cumulative release rate in each dissolution medium within 30 min was higher than 80%, much higher than that of FMN (6%) and FMN-NCs (40%); Cellular experiments confirm that the formulation has a high safety profile and significantly promotes cellular uptake. The results of pharmacokinetics and intestinal absorption in rats showed that the relative bioavailability of FMN-NCs and FMN-NCs loaded SMEDDS were (154.80 ± 3.76)% and (557.73 ± 32.88)%, respectively, and both of them significantly increased the rate and extent of absorption of the drug in intestinal segments. FMN-NCs loaded SMEDDS significantly enhanced the solubility and bioavailability of FMN.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563631","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":"Technological Strategies Applied to Pharmaceutical Systems for Intranasal Administration of Drugs Intended for Neurological Treatments: A Review","authors":"Maria Vitoria Gouveia Botan,&nbsp;Jéssica Bassi da Silva,&nbsp;Marcos Luciano Bruschi","doi":"10.1208/s12249-024-02974-9","DOIUrl":"10.1208/s12249-024-02974-9","url":null,"abstract":"<div><p>The complexity of treating neurological diseases has meant that new strategies have had to be developed to deliver drugs to the brain more efficiently and safely. Intranasal drug delivery is characterized by its ease of administration, safety, and rapid delivery directly from the nose to the brain. Several strategies have been developed to improve the delivery of drugs to the brain via nasal administration. These include the use of mucoadhesive and thermoresponsive polymers and their combination into polymer blends, as well as the use of liposomes, niosomes, and nano- and microemulsions. Therefore, this review focuses on technologies for developing pharmaceutical systems aimed at delivery via the nose to the brain, contributing to new treatments for difficult neurological disorders. Some of the most common and difficult-to-treat neurological conditions, the intranasal route of administration, and the anatomy of the nasal cavity have been discussed, as well as factors that may influence the absorption of drugs administered into the nose. The types of intranasal formulations and the devices that can be used to administer these products are also discussed in this review. Strategies for improving the transport of bioactive agents and increasing bioavailability are highlighted. The technologies discussed in this review can facilitate the development of formulations with improved properties, such as drug release and mucoadhesiveness, which have several advantages for patients requiring complex neurological treatments.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563658","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":"Strap-on Buoyant Device to Enhance Gastrointestinal Tract Retention of Felodipine Osmotic Pump Tablets","authors":"Qijia Ni,&nbsp;Zeru Li,&nbsp;Libumo Baqing,&nbsp;Tianfu Li,&nbsp;Huipeng Xu,&nbsp;Falan Li,&nbsp;Ningning Peng,&nbsp;Caifen Wang,&nbsp;Jianhua Lu,&nbsp;Zhigang Wang,&nbsp;Kai Wang,&nbsp;Chao Jiang,&nbsp;Li Wu,&nbsp;Ye Yang,&nbsp;Hua Zhou,&nbsp;Yongdong Gu,&nbsp;Jiwen Zhang","doi":"10.1208/s12249-024-02976-7","DOIUrl":"10.1208/s12249-024-02976-7","url":null,"abstract":"<div><p>Osmotic pump systems require prolonged retention time in the stomach to provide enhanced bioavailability and regulated release, which is quite challenging. This study used a three-dimensional printing (3DP) technique combined with a gastro-retentive floating device (GRFD) to extend the retention of the osmotic pump in the stomach and enhance its bioavailability. The strap-on buoyant device was fabricated by stereolithography 3DP and incorporated a felodipine osmotic pump tablet used in clinical practice, which enabled it to float in the stomach or dissolution media without any floating lag time. The components of the device were affixed using a snap-fix mechanism. GRFD dissolution study revealed a notable <i>in vitro</i> floating capability, lasting over 24 h, with a release profile similarity factor <i>f</i>₂ = 65.28 compared to the naked tablet dissolution profile. The pharmacokinetics of felodipine osmotic pump in beagles showed a C_max of 1.893 ng/mL, which increased to 4.511 ng/mL with GRFD. The delivery of an osmotic pump with GRFD enhanced the AUC_0−∞ of felodipine from 10.20 ng/mL·h to 26.54 ng/mL·h. In conclusion, the strap-on buoyant device has been successfully designed to enhance gastrointestinal tract retention of felodipine osmotic pumps and bioavailability in beagles.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563614","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 of Film-Forming Emulsions for Dermal and Transdermal Drug Delivery","authors":"Aideé Morales-Becerril,&nbsp;Liliana Aranda-Lara,&nbsp;Keila Isaac-Olive,&nbsp;Alejandra Ramírez-Villalva,&nbsp;Blanca Ocampo-García,&nbsp;Enrique Morales-Avila","doi":"10.1208/s12249-024-02942-3","DOIUrl":"10.1208/s12249-024-02942-3","url":null,"abstract":"<div><p>Drug delivery through the skin is a widely used therapeutic method for the treatment of local dermatologic conditions. Dermal and transdermal methods of drug delivery offer numerous advantages, but some of the most important aspects of drug absorption through the skin need to be considered. Film-forming systems (FFS) represent a new mode of sustained drug delivery that can be used to replace traditional topical formulations such as creams, ointments, pastes, or patches. They are available in various forms, including solutions, gels, and emulsions, and can be categorised as film-forming gels and film-forming emulsions. Film-forming emulsions (FFE) are designed as oil-in-water (O/W) emulsions that form a film with oil droplets encapsulated in a dry polymer matrix, thus maintaining their dispersed nature. They offer several advantages, including improved solubility, bioavailability and chemical stability of lipophilic drugs. In addition, they could improve the penetration and diffusion of drugs through the skin and enhance their absorption at the target site due to the nature of the components used in the formulation. The aim of this review is to provide an up-to-date compilation of the technologies used in film-forming emulsions to support their development and availability on the market as well as the development of new pharmaceutical forms.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563630","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 Adaptive Approach in Polymer-Drug Nanoparticle Engineering using Slanted Electrohydrodynamic Needles and Horizontal Spraying Planes","authors":"Amna Ali,&nbsp;Saman Zafar,&nbsp;Manoochehr Rasekh,&nbsp;Tahir Ali Chohan,&nbsp;Francesca Pisapia,&nbsp;Neenu Singh,&nbsp;Omar Qutachi,&nbsp;Muhammad Sohail Arshad,&nbsp;Zeeshan Ahmad","doi":"10.1208/s12249-024-02971-y","DOIUrl":"10.1208/s12249-024-02971-y","url":null,"abstract":"<div><p>The present study focuses on the adaptive development of a key peripheral component of conventional electrohydrodynamic atomisation (EHDA) systems, namely spraying needles (also referred to as nozzles or spinnerets). Needle geometry and planar alignment are often overlooked. To explore potential impact, curcumin-loaded polylactic-co-glycolic acid (PLGA) and methoxypolyethylene glycol amine (PEG)-based nanoparticles were fabricated. To elucidate these technological aspects, a horizontal electrospraying needle regime was adapted, and three formulations containing different polymeric ratios of PLGA: PEG (50:50, 75:25, and 25:75) were prepared and utilised. Furthermore, processing head tip geometries e.g. blunt (a flat needle exit) or slanted (a 45° inclination angle), were subjected to various flow rates (5 µL-100 µL). Successful engineering of curcumin-loaded polymeric nanoparticles (&lt; 150 nm) was observed. In-<i>silico</i> analysis demonstrated stable properties of curcumin, PEG and PLGA (molecular docking studies) and fluid flow direction towards the Taylor-Cone (also known as the stable jet mode), was shown by the assessment of fluid dynamics simulations in various needle outlets. Curcumin-loaded nanoparticles were characterised using an array of methods including Scanning electron microscopy, Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, as well as their contact angles, encapsulation efficiencies and finally release patterns. The discrepancy when spraying with blunt and angled needles was evidenced by electron micrographs and deposition patterns. Spraying plumes utilising slanted needles enhanced particle collection efficiency and distribution of resultant atomised structures. In addition to needle design, fine-tuning the applied voltage and flow rate impacted the electrospraying process. The coefficient of variation was calculated as 30.5% and 25.6% for blunt and angled needle outlets, respectively, presenting improved particle uniformity with the employment of angled needle tips (8-G needle at 25 µL). The interplay of processing parameters with the utilisation of a slanted exit at a capillary optimised the spray pattern and formation of desired nanoparticulates. These demonstrate great applicability for controlled deposition and up-scaling processes in the pharmaceutical industry. These advances elaborate on EHDA processes, indicating a more cost-effective and scalable approach for industrial applications, facilitating the generation of a diverse range of particle systems in a controlled and more uniform fashion.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543026","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":"Non-Invasive Techniques of Nose to Brain Delivery Using Nanoparticulate Carriers: Hopes and Hurdles","authors":"Mansi Butola,&nbsp;Nidhi Nainwal","doi":"10.1208/s12249-024-02946-z","DOIUrl":"10.1208/s12249-024-02946-z","url":null,"abstract":"<p>Intranasal drug delivery route has emerged as a promising non-invasive method of administering drugs directly to the brain, bypassing the blood–brain barrier (BBB) and blood-cerebrospinal fluid barriers (BCSF). BBB and BCSF prevent many therapeutic molecules from entering the brain. Intranasal drug delivery can transport drugs from the nasal mucosa to the brain, to treat a variety of Central nervous system (CNS) diseases. Intranasal drug delivery provides advantages over invasive drug delivery techniques such as intrathecal or intraparenchymal which can cause infection. Many strategies, including nanocarriers liposomes, solid-lipid NPs, nano-emulsion, nanostructured lipid carriers, dendrimers, exosomes, metal NPs, nano micelles, and quantum dots, are effective in nose-to-brain drug transport. However, the biggest obstacles to the nose-to-brain delivery of drugs include mucociliary clearance, poor drug retention, enzymatic degradation, poor permeability, bioavailability, and naso-mucosal toxicity. The current review aims to compile current approaches for drug delivery to the CNS via the nose, focusing on nanotherapeutics and nasal devices. Along with a brief overview of the related pathways or mechanisms, it also covers the advantages of nasal drug delivery as a potential method of drug administration. It also offers several possibilities to improve drug penetration across the nasal barrier. This article overviews various <i>in-vitro, ex-vivo</i>, and <i>in-vivo</i> techniques to assess drug transport from the nasal epithelium into the brain.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543027","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}