European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Unleashing the antitumor power of cyclophosphamide by arabinogalactan and aptamer conjugation","authors":"Tatiana N. Zamay ,&nbsp;Olga S. Kolovskaya ,&nbsp;Galina S. Zamay ,&nbsp;Andrey K. Kirichenko ,&nbsp;Natalia A. Luzan ,&nbsp;Sergey S. Zamay ,&nbsp;Nadezhda A. Neverova ,&nbsp;Elena N. Medvedeva ,&nbsp;Vasilii A. Babkin ,&nbsp;Dmitry V. Veprintsev ,&nbsp;Irina A. Shchugoreva ,&nbsp;Anna S. Kichkailo","doi":"10.1016/j.ejpb.2024.114531","DOIUrl":"10.1016/j.ejpb.2024.114531","url":null,"abstract":"<div><div>Cyclophosphamide (CPA) (2-oxo-2-di(β-chloroethyl)amino tetrahydro-2,1,3-phosphoxazine) is an alkylating cytostatic compound with a broad spectrum of antitumor activity. Despite its efficacy, the clinical application of CPA is hindered by the significant occurrence of adverse side effects. To address these limitations, a promising approach involves the mechanochemical treatment of CPA with arabinogalactan (AG) to facilitate the dispersion of the drug within the AG matrix. AG stands out from other polymers due to its uniformity, low molecular weight, water solubility, and ability to form drug conjugates, thereby enhancing their therapeutic potency. Moreover, AG possesses immune-modulating properties that have the potential to counteract the immunosuppressive effects induced by CPA. By means of mechanical treatment, we successfully obtained CPA-AG complexes with a CPA:AG ratio of 1:10. These complexes were further modified with As42 aptamers that specifically target Erlich ascites cells. Aptamers, a novel class of oligonucleotide ligands obtained through SELEX technology, possess high affinity and specificity for binding to various receptors. An ascitic form of Ehrlich carcinoma was chosen as an in vitro and <em>in vivo</em> tumor model due to its notable drug resistance. In vitro and <em>in vivo</em> evaluations were conducted to compare the antitumor activity of both the CPA-AG and CPA-AG-As42 complexes with pure CPA. In vitro experiments revealed that the CPA-AG complex displayed superior antitumor activity compared to pure CPA, leading to complete tumor cell death primarily through necrosis. Notably, no toxic effects were observed with the CPA-AG and CPA-AG-As42 complexes, and they significantly prolonged the lifespan of tumor-bearing mice by more than 3.5 times. Histological studies further supported the antitumor efficacy of these complexes. These results underscore the potential of utilizing CPA-AG mechanocomposites, functionalized with aptamers, for the targeted delivery of CPA to tumors.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114531"},"PeriodicalIF":4.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and characterization of novel fast-dissolving pentobarbital suppositories for pediatric procedural sedation and comparison with lipophilic formulations","authors":"Aurelien Freisz ,&nbsp;Imen Dhifallah ,&nbsp;Yoann Le Basle ,&nbsp;Mireille Jouannet ,&nbsp;Philip Chennell ,&nbsp;Ghislain Garrait ,&nbsp;Eric Beyssac ,&nbsp;Yassine Bouattour ,&nbsp;Valérie Sautou","doi":"10.1016/j.ejpb.2024.114532","DOIUrl":"10.1016/j.ejpb.2024.114532","url":null,"abstract":"<div><div>For pediatric radiological procedures (RP), pentobarbital sodium (PNa) can be used orally or rectally to replace intravenous anesthesia. Since no commercial PNa suppositories exist, they must be prepared by compounding pharmacies. This study aims to develop fast-dissolving PNa suppositories for fast pharmacological activity during RP. We prepared gelatin (G), gelatin/polyethylene glycol 4000 (GP), and polyethylene glycol 4000 (P) suppositories, with and without pH adjustment, and assessed their dosage uniformity (DU), softening time, rupture resistance, and <em>in-vitro</em> dissolution. An optimal formulation was selected, and PNa release was compared to that of fat-based suppositories using dissolution tests. Additionally, the quality control process (analytical performance, safety/eco-friendliness and productivity/practical effectiveness) of these formulas were compared using a RGB method. All hydrophilic formulas (HF) met the DU requirement (AV &lt; 8 %) except for P (AV 15.62 ± 4 %). pH adjustment enhanced G and GP suppositories resistance to 2.2 ± 0.2 kg and 2.0 ± 0.3 kg, respectively, and allowed <strong>100 % release</strong> of PNa in under 10 min. In contrast, lipophilic formulas released less than 80 % of PNa at best after 120 min. These results show the biopharmaceutical suitability of HF for RP compared to lipophilic ones, but a pharmacokinetic study is needed to confirm data.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114532"},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Authors’ reply to comments on “Improved photostability, solubility, hygroscopic stability and antimicrobial activity of fleroxacin by synthesis of fleroxacin-D-tartaric acid pharmaceutical salt”","authors":"Lixin Liu,&nbsp;Yuning Wang,&nbsp;Jiuyi Sun,&nbsp;Yunan Zhang,&nbsp;Xiangyu Zhang,&nbsp;Lili Wu,&nbsp;Yingli Liu,&nbsp;Xuan Zhang,&nbsp;Yidi Xia,&nbsp;Qiumei Zhang,&nbsp;Ning Gao","doi":"10.1016/j.ejpb.2024.114519","DOIUrl":"10.1016/j.ejpb.2024.114519","url":null,"abstract":"<div><div>This article responds to Dr. Shayanfar’s comment “Improvement of photostability, solubility, hygroscopic stability and antimicrobial activity of fleroxacin by synthesizing fleroxacin-D-tartaric acid pharmaceutical salt”. We rationalized and explained the solubility study portion of the published novel pharmaceutical salt (fleroxacin-D-tartaric acid, FL-D-TT). This confirms that the results of the solubility studies of fleroxacin (FL) and its pharmaceutical salt (FL-D-TT) in our published articles are true and accurate and consistent with the theoretical analysis.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114519"},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation strategies, preparation methods, and devices for pulmonary delivery of biologics","authors":"Kai Berkenfeld ,&nbsp;Simone Carneiro ,&nbsp;Carolina Corzo ,&nbsp;Flavia Laffleur ,&nbsp;Sharareh Salar-Behzadi ,&nbsp;Benjamin Winkeljann ,&nbsp;Golbarg Esfahani","doi":"10.1016/j.ejpb.2024.114530","DOIUrl":"10.1016/j.ejpb.2024.114530","url":null,"abstract":"<div><div>Biological products, including vaccines, blood components, and recombinant therapeutic proteins, are derived from natural sources such as humans, animals, or microorganisms and are typically produced using advanced biotechnological methods. The success of biologics, particularly monoclonal antibodies, can be attributed to their favorable safety profiles and target specificity. However, their large molecular size presents significant challenges in drug delivery, particularly in overcoming biological barriers. Pulmonary delivery has emerged as a promising route for administering biologics, offering non-invasive delivery with rapid absorption, high systemic bioavailability, and avoidance of first-pass metabolism. This review first details the anatomy and physiological barriers of the respiratory tract and the associated challenges of pulmonary drug delivery (PDD). It further discusses innovations in PDD, the impact of particle size on drug deposition, and the use of secondary particles, such as nanoparticles, to enhance bioavailability and targeting. The review also explains various devices used for PDD, including dry powder inhalers (DPIs) and nebulizers, highlighting their advantages and limitations in delivering biologics. The role of excipients in improving the stability and performance of inhalation products is also addressed. Since dry powders are considered the suitable format for delivering biomolecules, particular emphasis is placed on the excipients used in DPI development. The final section of the article reviews and compares various dry powder manufacturing methods, clarifying their clinical relevance and potential for future applications in the field of inhalable drug formulation.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114530"},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 3D printed microneedles of varied needle geometries and lengths, designed to improve the dermal delivery of topically applied psoriasis treatments","authors":"Larissa Carine Pünnel ,&nbsp;Maria Palmtag ,&nbsp;Dominique Jasmin Lunter ,&nbsp;Jillian L Perry","doi":"10.1016/j.ejpb.2024.114523","DOIUrl":"10.1016/j.ejpb.2024.114523","url":null,"abstract":"<div><div>The aim of this study was to investigate the impact of using microneedle patches in addition to topical therapy for the treatment of psoriasis. Using continuous liquid interface production (CLIP) 3D printing we manufactured round microneedle array patches (MAPs) with a diameter of 14 mm. Needle geometries were varied from square pyramidal, conical, and obelisk, with varied needle lengths of 400 µm, 600 µm, 800 µm, or 1000 µm. MAPs were characterized for force to fracture, skin penetration, skin damage, as well as their ability to deliver a novel oleogel-based corticosteroid (betamethasone dipropionate (BDP) formulation into <em>ex-vivo</em> porcine skin. We found that the obelisk shaped MAPs are more durable compared to the conical and square pyramidal-shaped MAPs. When the obelisk shaped MAPs were used in combination with the oleogel-based BDP formulation, the amount of BDP penetrating the skin was significantly increased with greater needle lengths.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114523"},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis and mechanistic insights into polysorbate 80 stability differences in biopharmaceutical buffer systems","authors":"Zhuan Cheng ,&nbsp;Pengzhen Wang ,&nbsp;Luting Liu,&nbsp;Quanmin Chen,&nbsp;Jeremy Guo","doi":"10.1016/j.ejpb.2024.114521","DOIUrl":"10.1016/j.ejpb.2024.114521","url":null,"abstract":"<div><div>Polysorbate 80 (PS80) is a non-ionic surfactant extensively utilized in biopharmaceutical formulations for stabilizing proteins. However, PS80 degradation has become a widespread concern throughout the industry over the past decade. In this work, the impact of most frequently employed pH/buffer systems on the stability of PS80 was assessed. PS80 degraded fastest in histidine buffer, followed by acetate and succinate buffers, whereas it remained stable in citrate, phosphate and tris buffers. When there was PS80 degradation, the extent of degradation was found to be pH-dependent. The predominant degradation pathway was oxidation mainly triggered by metal ions. The varying stability of PS80 across different pH/buffer systems was attributed to the role of buffer agents, which can either promote or inhibit the oxidation process through their interactions with metal ions. Specifically, buffers except histidine exhibited metal ion chelation similar to ethylenediaminetetraacetic acid (EDTA), which can suppress the oxidation of PS80, although the effectiveness of chelation varies to different extents. Furthermore, the binding capacity appeared stronger at higher pH in acetate and succinate buffers. Conversely, histidine was reported to form pro-oxidant complexes with metal ions to accelerate PS80 degradation, especially at higher pH levels. Our work for the first time offers a comprehensive understanding of PS80 oxidation in biopharmaceutical buffer systems. This provides a strong foundation for buffer and excipient selection in parenteral formulations.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114521"},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Process analytical technology based quality assurance of API concentration and fiber diameter of electrospun amorphous solid dispersions","authors":"Bettina Fazekas,&nbsp;Orsolya Péterfi,&nbsp;Dorián László Galata,&nbsp;Zsombor Kristóf Nagy,&nbsp;Edit Hirsch","doi":"10.1016/j.ejpb.2024.114529","DOIUrl":"10.1016/j.ejpb.2024.114529","url":null,"abstract":"<div><div>In this study, a novel quality assurance system was developed utilizing Process analytical technology (PAT) tools and artificial intelligence (AI). Our goal was to monitor the critical quality attributes (CQAs) like drug concentration, morphology and fiber diameter of electrospun amorphous solid dispersion (ASD) formulations with fast at-line techniques. Doxycycline-hyclate (DOX), a tetracycline-type antibiotic was used as a model drug with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as the matrix excipient. The water-based formulations were electrospun with high-speed electrospinning (HSES). Raman and NIR sensors and machine vision-based color measurement techniques were employed to accurately determine the drug concentration. Given that morphology can influence the solubility of the drug, a convolutional neural network (CNN)-based AI model was developed to examine this property and detect manufacturing defects. Additionally, the diameter of electrospun fibrous samples was measured using camera images and a trained AI model, enabling rapid analysis of fiber diameter with results similar to that of scanning electron microscopy (SEM). These methods and models demonstrate potential in-line analytical tools, offering rapid, cheap and non-destructive analysis of ASD formulations.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114529"},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation of dual drug-loaded polymer nanoconjugate to enhance treatment efficacy for ovarian cancer cells","authors":"Buket Ozel ,&nbsp;Senay Sanlier ,&nbsp;Cumhur Gunduz ,&nbsp;Nur Selvi Gunel","doi":"10.1016/j.ejpb.2024.114526","DOIUrl":"10.1016/j.ejpb.2024.114526","url":null,"abstract":"<div><div>Ovarian cancer is the deadliest gynecological malignancy, representing 2.5 % of all female cancers and accounting for 5 % of female cancer-related fatalities. Despite numerous strategies in its treatment, the disease shows a high recurrence rate and a low survival rate. Consequently, there is a growing focus on targeted therapies in ovarian cancer treatment. It is well-known that VEGFR and LPA pathways undergo alterations in ovarian cancer and stimulate survival, adhesion, migration, invasion, tumor growth and angiogenesis. Cabozantinib (CBZ) is a multi-receptor tyrosine kinase inhibitor that effectively targets MET, VEGFR-1, 2, 3, FLT3, c-KIT, and RET. Ki16425 is a selective inhibitor of LPA receptors 1, 2, and 3. Therefore, targeting LPA receptors and combining with VEGFR inhibitor is a strategic approach for ovarian cancer treatment. In this study, it was aimed to prepare polymer-drug nanoconjugate for both VEGFR and LPAR inhibition. For this, O-(2-Carboxyethyl) polyethylene glycol (PEG₅₀₀₀) which advantages are known in cancer studies, was chosen as the carrier system, and a nanoconjugate containing Ki16425 and CBZ (Ki-PEG-CBZ) was synthesized and its potential was evaluated. Initially, CBZ and Ki16425 were conjugated to the PEG₅₀₀₀ through pH-sensitive hydrazone and ester bonds. After nanoconjugate characterization, in vitro release and its ovarian cancer treatment potential were evaluated on A2780, OVCAR3 and SKOV3 ovarian cancer cell lines. A nanoconjugate was obtained with a particle size of 169 ± 15.23 nm, a zeta potential of −13.5 ± 1.21 mV, and a release profile lasting 48 h, containing CBZ and Ki16425 with drug loading efficiencies of 73.71 ± 0.53 % and 77.72 ± 2.51 %, respectively. In vitro studies have demonstrated that Ki-PEG-CBZ is highly effective against ovarian cancer. We suggest that the developed polymer-drug nanoconjugate is an effective and safe nanoconjugate for the treatment of ovarian cancer.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114526"},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluoroamphiphiles for enhancing immune response of subunit vaccine against SARS-CoV-2","authors":"Yuan Li ,&nbsp;Ziyao Kang ,&nbsp;Xuefeng Zhang ,&nbsp;Yun Sun ,&nbsp;Zibo Han ,&nbsp;Hao Zhang ,&nbsp;Zhaoming Liu ,&nbsp;Yu Liang ,&nbsp;Jing Zhang ,&nbsp;Jin Ren","doi":"10.1016/j.ejpb.2024.114528","DOIUrl":"10.1016/j.ejpb.2024.114528","url":null,"abstract":"<div><div>In recent decades, protein-based therapy has garnered valid attention for treating infectious diseases, genetic disorders, cancer, and other clinical requirements. However, preserving protein-based drugs against degradation and denaturation during processing, storage, and delivery poses a formidable challenge. Herein, we designed a novel fluoroamphiphiles polymer to deliver protein. Two different formulations of nanoparticles, cross-linked (CNP) and micelle (MNP) polymer, were prepared rationally by disulfide cross-linked and thin-film hydration techniques, respectively. The size, zeta potential, and morphology of both formulations were characterized and the delivery efficacy of both <em>in vitro</em> and <em>in vivo</em> was also assessed. The <em>in vitro</em> findings demonstrated that both formulations effectively facilitated protein delivery into various cell lines. Moreover, <em>in vivo</em> experiments revealed that intramuscular administration of the two formulations loaded with a SARS-CoV-2 recombinant receptor-binding domain (RBD) vaccine induced robust antibody responses in mice without adding another adjuvant. These results highlight the potential use of our carrier system as a safe and effective platform for the <em>in vivo</em> delivery of subunit vaccines.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114528"},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T7 Peptide-modified macrophage membrane-coated nanoplatform for enhanced glioma treatment","authors":"Xuanrong Sun ,&nbsp;Dehui Xie ,&nbsp;Zhao Lou ,&nbsp;Yujie Zhou ,&nbsp;Ming Li ,&nbsp;Qingyong Li ,&nbsp;Yue Cai","doi":"10.1016/j.ejpb.2024.114527","DOIUrl":"10.1016/j.ejpb.2024.114527","url":null,"abstract":"<div><div>The efficient and secure delivery of intravenous chemotherapeutic agents across the blood–brain barrier (BBB) to the precise location of a brain tumor is a crucial element in glioma treatment. Herein, we introduce a biomimetic nanoplatform (T7-M-C/S) comprising a core made up of irinotecan hydrochloride (CPT11) and its bioactive metabolite, 7-Ethyl-10-hydroxycamptothecin (SN38), surrounded by a layer of T7-peptide-modified macrophage membrane. CPT11 spontaneously assembles with SN38 into stable and water-dispersible nanoparticles (C/S), greatly enhancing the water solubility of SN38. The integration of the modified peptide with the inherent proteins expressed by macrophage cells confers the nanoplatform with enhanced bioavailability and robust glioma-targeting abilities, ultimately resulting in superior therapeutic outcomes. These discoveries highlight a drug delivery system characterized by a high drug loading capacity, leveraging the macrophage membrane, and promising significant potential for glioma treatment.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114527"},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}