European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Corrigendum to “Preparation and evaluation of celecoxib lyophilized orally disintegrating tablets with high bioavailability” [Eur. J. Pharm. Biopharm. 213 (2025) 114756]","authors":"Shuai Sun , Mengjun Wang , Jin Chen , Xiaoli Ju , Furong Zhang , Meilin He , Dongfang Cheng , Shumeng Kong","doi":"10.1016/j.ejpb.2025.114760","DOIUrl":"10.1016/j.ejpb.2025.114760","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114760"},"PeriodicalIF":4.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247156","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":"Effect of pH, buffers, molarity, and temperature on solution state degradation of semaglutide using LC-HRMS: A preformulation protocol for peptide drug delivery","authors":"Adarsh Malgave ,&nbsp;Sideequl Akbar ,&nbsp;Anumol Joseph ,&nbsp;Dande Aishwarya ,&nbsp;Ramalingam Peraman ,&nbsp;Rajkumar Malayandi","doi":"10.1016/j.ejpb.2025.114780","DOIUrl":"10.1016/j.ejpb.2025.114780","url":null,"abstract":"<div><div>Semaglutide (SGL), a long-acting GLP-1 (Glucagon-like peptide) receptor agonist, is a 31-amino acid peptide modified with a C18 fatty diacid for albumin binding. Peptides are fragile and susceptible to degradation during formulation, storage, and transportation. The degradation of peptides resulted in the formation of impurities that may impact safety, efficacy, immunogenicity, and regulatory compliance. The present study examines the effects of pH, temperature, buffer species, and molarity on the stability of SGL. Reverse-phase ultra-performance liquid chromatography (RP-UPLC) was used to separate impurities, followed by liquid chromatography high-resolution mass spectrometry (LC-HRMS) for their molecular weight. The stress stability studies were conducted in thermal stress conditions at 25 °C, 40 °C, 60 °C (for 28 days), and 80 °C (for 7 days). The influence of pH, buffer strength, and buffer species on the degradation of SGL was investigated at 25 °C and 40 °C. The degradation of SGL resulted in thirteen known impurities, and their fragments were identified using LC-MS analysis. Six impurities, such as impurity 4 (<em>m</em>/<em>z</em> = 2717.21), impurity 5 (<em>m</em>/<em>z</em> = 4129.64), impurity 7 (<em>m</em>/<em>z</em> = 3762.28), impurity 8 (<em>m</em>/<em>z</em> = 3456.94), impurity 12 (<em>m</em>/<em>z</em> = 2967.5), and impurity 13 (<em>m</em>/<em>z</em> = 839), were formed across all the testing conditions. These impurities were relatively stable when compared to other formed impurities. The influence of pH on the thermal stability of SGL was demonstrated. The impurities, such as impurity 2 (<em>m</em>/<em>z</em> = 845.13), impurity 9 (<em>m</em>/<em>z</em> = 3397.76), impurity 10 (<em>m</em>/<em>z</em> = 701.0), and impurity 11 (<em>m</em>/<em>z</em> = 4125.7), were absent across all pH conditions, but these impurities were found when water was used as a solvent. The study demonstrated that the pH was a key factor for the thermal degradation of SGL. The degradation pathways were elucidated based on the mass data for known masses. The solution-state thermal stress studies were performed to select the buffer for formulating long-acting PLGA formulations. Moreover, the solution state stress stability data could be helpful for optimization of the pharmaceutical process, in vivo stability of SGL in muscles, storage and transportation of finished products, and determining the shelf-life.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114780"},"PeriodicalIF":4.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254313","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":"Enhanced chemotherapy in thyroid carcinoma: A MnO2-silica nanoreactor activated by H2O2/GSH for hypoxia relief","authors":"Menghan Wang ,&nbsp;Zhongchao Mai ,&nbsp;Zhongna Ma ,&nbsp;Wei Xia ,&nbsp;Yanan Song","doi":"10.1016/j.ejpb.2025.114776","DOIUrl":"10.1016/j.ejpb.2025.114776","url":null,"abstract":"<div><div>Thyroid cancer is the most prevalent endocrine cancer that threats to the health of human being seriously, and characterized with resistance to various therapeutic modalities. The therapeutic efficacy of oxygen-dependent chemotherapy is hindered by hypoxia within tumor tissue heavily. Therefore, the supply of oxygen in situ is an effective strategy to improve the chemotherapeutic outcomes. The emergence of nanomedicine open an novel gate for tumor treatment, however, there is still lack of nanoplatforms for sufficient oxygen supply to improve the chemotherapeutic efficiency. In this study, MnO₂ nanoenzyme was decorated onto glutathione (GSH)-sensitive mesoporous silica, and an intelligent nanoreactor was subsequently constructed by loading saikosaponin-d (SSD) into the mesopore channels and modified with folic acid. Upon targeted delivery to thyroid tumor cells, the Mn²⁺ hydrolyzed from nanoreactor facilitated the decomposition of endogenous H₂O₂ in the tumor, alleviating the hypoxic tumor microenvironment. Simultaneously, the tetrasulfide bonds of silica were cleaved by cytoplasmic L-GSH, releasing the loaded cargoes. Consequently, a remarkably enhanced chemotherapeutic effect of SSD was achieved both <em>in vitro</em> and <em>in vivo</em>. The mechanism underlying the tumor cell–killing effect was attributed to the generation of copious amounts of O₂ <em>via</em> disrupting the PI3K/Akt signaling pathway <em>via</em> transcriptome sequencing. The outstanding biocompatibility of the H₂O₂/GSH dual-sensitive Mn-based nanoreactor offered an exceptional chemotherapeutic effect against malignant tumors.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114776"},"PeriodicalIF":4.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254450","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":"Overcoming drug resistance in osteosarcoma with MTX-CuB-NLC: An in vitro and in vivo study","authors":"Hao Li ,&nbsp;Tingqi Bao ,&nbsp;Xinyi Huang ,&nbsp;Jianwen Zhou ,&nbsp;Ziyu Zhang ,&nbsp;Xuefeng Wang ,&nbsp;Weifu You ,&nbsp;Lixin Cao ,&nbsp;Cuiyan Han","doi":"10.1016/j.ejpb.2025.114779","DOIUrl":"10.1016/j.ejpb.2025.114779","url":null,"abstract":"<div><div>Osteosarcoma (OS) is the predominant bone tumor affecting pediatric and adolescent populations. The standard treatment regimen involves preoperative chemotherapy, surgical intervention, and postoperative chemotherapy. Methotrexate (MTX) serves as the first-line pharmacological agent for OS treatment; however, the emergence of tumor resistance to chemotherapeutic agents poses a significant challenge. Cucurbitacin B (CuB) exhibits intrinsic anti-OS properties and can synergistically enhance OS suppression by reversing drug resistance and augmenting the therapeutic effects of MTX. Nevertheless, the clinical application of CuB and MTX is hindered by their low aqueous solubility, necessitating the development of an effective drug delivery system to precisely target tumor tissues and maximize therapeutic efficacy. Consequently, this study focuses on the development of a nanostructured lipid carrier (NLC) co-loaded with MTX and CuB (MTX-CuB-NLC) to address these limitations. MTX-CuB-NLC is characterized as a spherical nanoparticle with a mean particle size of 44.13 ± 1.40 nm, a polydispersity index (PDI) of 0.279 ± 0.120, and a zeta potential of −17.10 ± 4.98 mV. The encapsulation efficiency (EE%) and drug loading (DL%) were determined to be 61.03 ± 2.40 % and 0.25 ± 0.02 % for MTX, and 81.02 ± 1.61 % and 0.23 ± 0.02 % for CuB, respectively. The formulation demonstrated substantial storage stability over a 14-day period. In vitro release studies indicated that MTX-CuB-NLC possesses sustained release capabilities. Furthermore, the nanoparticle exhibited significantly enhanced uptake and cytotoxicity against U-2 OS cells compared to the free drug. Notably, MTX-CuB-NLC displayed pronounced cytotoxic effects on methotrexate-resistant U-2 OS cells (U-2 OS/MTX), underscoring its potential to induce apoptosis and circumvent multidrug resistance in these cells. In an OS nude mouse model exhibiting drug resistance, MTX-CuB-NLC demonstrated superior tumor targeting and suppression efficacy. This research has culminated in the development of an effective continuous drug delivery system for osteosarcoma, presenting a promising strategy to combat drug resistance in this malignancy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114779"},"PeriodicalIF":4.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257710","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":"Peptide-loaded chitosan nanoparticles improve mitochondrial and cognitive functions via inhibition of Aβ-ABAD interaction in Alzheimer’s disease","authors":"Yomna A. Youssef ,&nbsp;Salma N. Tammam ,&nbsp;Basma M. Elshenawy ,&nbsp;Shaista Ilyas ,&nbsp;Alaa A. Gad ,&nbsp;Karin S. Farag ,&nbsp;Sanjay Mathur ,&nbsp;Reham M. Abdel-Kader","doi":"10.1016/j.ejpb.2025.114778","DOIUrl":"10.1016/j.ejpb.2025.114778","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most prevalent form of dementia. Mitochondrial dysfunction is recognized among the earliest pathological events in AD, and is closely-linked with the accumulation of amyloid-beta (Aβ) plaques which is a well-established hallmark of AD. The interplay between the two converges on the interaction of Aβ with the mitochondrial enzyme Aβ-binding alcohol dehydrogenase (ABAD), and the formation of Aβ-ABAD complex. This leads to the suppression of the normal function of ABAD, and elicits a number of detrimental events such as the excessive generation of reactive oxygen species (ROS) resulting in apoptosis of neuronal cells. To intercept the Aβ-ABAD interaction, a decoy peptide (DP) was employed, and was loaded into polymeric chitosan nanoparticles (CSNPs) for efficient delivery across the blood–brain barrier (BBB). <em>In vivo</em> studies on control and neuroinflammatory mouse models confirmed that NPs of the smaller size (SNPs; 59 ± 6 nm) accumulated in the brain with minimal off-target delivery. Unlike free DP, DP-loaded SNPs significantly improved cognitive functions as depicted by the modified Y-maze test. The DP also had protective effects on the mitochondria that were associated with a decrease in Aβ, an increase in ATP and a normalization in SOD activity. Additionally, the restoration of ABAD normal function was reflected by elevated estradiol levels. These findings indicate that the inhibition of Aβ-ABAD complex ameliorates Aβ-induced toxicity in AD, consequently enhancing both mitochondrial and cognitive functions.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114778"},"PeriodicalIF":4.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247159","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":"Mechanisms of polysorbate 80 oxidation: Acetate and Fe(III) mediated near UV and visible light degradation enhanced by free fatty acids","authors":"Yaqi Wu ,&nbsp;David Richards ,&nbsp;Yilue Zhang ,&nbsp;Lin Zhang ,&nbsp;Steve W. Dodd ,&nbsp;Christian Schöneich","doi":"10.1016/j.ejpb.2025.114763","DOIUrl":"10.1016/j.ejpb.2025.114763","url":null,"abstract":"<div><div>Polysorbate 80 (PS80) is a widely used nonionic surfactant in biopharmaceutical formulations. PS80 is prone to chemical degradation, potentially resulting in loss of surfactant properties essential for the stability of pharmaceutical formulations. A deep understanding of PS80 stability is critical to maintaining drug efficacy and safety. While general mechanisms of oxidation are known, specific mechanistic information on the initiation of PS80 oxidation in formulations is lacking. Here, we report on novel mechanisms of photo-degradation of PS80 in pharmaceutical buffers such as acetate, succinate, and adipate, containing Fe(III). Photo-degradation was monitored by fluorescence micelle assay (FMA) and mass spectrometry (MS). The mechanistic investigation suggests an <em>intra</em>-micellar PS80 photo-degradation mechanism, wherein buffer-derived carbon-centered radicals, generated from light-induced ligand-to-metal-charge-transfer (LMCT) and decomposition of Fe(III)-carboxylate complexes, enter the PS80 micelles and initiate degradation. Critical for the extent of photo-degradation is the presence of small levels of free fatty acids (FFAs), such as can be present in commercial multi-compendial PS80, facilitating the access of radicals into micelles via complexing with Fe(III) on the micelle surface.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114763"},"PeriodicalIF":4.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247158","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":"A questionnaire survey on the barriers regarding pharmaceutical excipients during pediatric drug development","authors":"Jumpei Saito,&nbsp;Hidefumi Nakamura,&nbsp;Miki Akabane,&nbsp;Akimasa Yamatani","doi":"10.1016/j.ejpb.2025.114775","DOIUrl":"10.1016/j.ejpb.2025.114775","url":null,"abstract":"<div><div>It is unclear whether there have been any problems caused by excipients in the development of pediatric drugs. In this study, we investigated the current issues caused by excipients in developing pediatric formulations. The current issues and challenges related to excipients in pediatric drug development and the sources of information on excipients were investigated through a questionnaire sent to the 38 pharmaceutical companies that are members of the Japan Pharmaceutical Manufacturers Association. Twelve pharmaceutical companies with experience in developing pediatric formulations faced difficulties due to uncertain information on the suitability of excipients for pediatrics, and four companies faced difficulties due to different regulations on excipients in different countries. Uncertainty about the maximum acceptable dose and regulatory differences between countries were also cited as barriers. Regarding excipient databases, the United States Food and Drug Administration Inactive Ingredients Database and the European Safety and Toxicity of Excipients for Paediatrics database have been used for national and international pediatric drug development. The drawbacks of both international databases were the lack of information on excipients commonly used in Japan and the historically used maximum dose for each excipient. Future improvements in database information and clarification and standardization of the excipient regulatory process will be required.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114775"},"PeriodicalIF":4.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247154","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":"Co-embedding of curcumin and gold nanoparticles with ZIF-8 nanoparticles for the treatment of liver cancer and its impact on metabolomics","authors":"Xiaohui Wang ,&nbsp;Lin Zhou ,&nbsp;Yingying Shi ,&nbsp;Wang Wang ,&nbsp;Peng Li ,&nbsp;Rui Cui ,&nbsp;Yajuan Wu ,&nbsp;Feng Wang ,&nbsp;Qiuzheng Du","doi":"10.1016/j.ejpb.2025.114773","DOIUrl":"10.1016/j.ejpb.2025.114773","url":null,"abstract":"<div><div>The mortality rate of primary liver malignant tumors is very high. Curcumin (Cur) is one of the most commonly used drugs for the treatment of liver cancer. However, due to its low bioavailability, nano-drug delivery systems are rapidly developing. Zeolitic imidazolate framework-8 (ZIF-8), is pH-sensitive and biodegradable in acidic environments, providing a very suitable platform for drug delivery. Here, the anti-tumor properties of Cur and the anti-inflammatory properties of gold nanoparticles (Au NPs) were integrated and encapsulated in ZIF-8 material to prepare a composite drug delivery system (Cur/Au@ZIF-8). The prepared materials were characterized by scanning electron microscopy and elemental analysis, transmission electron microscopy, and powder X-ray diffraction. The drug loading efficiency of Cur in this delivery system reached 47.16 %. The drug release curve showed that the release rate of Cur/Au@ZIF-8 was faster at pH 5.5, with a release rate of 72.34 %. Ultrasound-guided in situ liver cancer models were constructed in SD rats to investigate the <em>in vivo</em> anti-tumor effects of Cur/Au@ZIF-8 and its impact on the metabolomics of tumor-bearing rats before and after treatment. <em>In vivo</em> results indicated that Cur/Au@ZIF-8 showed better anti-tumor effects, with a tumor inhibition rate of 46.81 %. After treatment, 26 key differential metabolites (p &lt; 0.05) were identified from expression patterns and metabolic pathways, which were mainly related to fatty acid metabolism. This treatment strategy provides a reference for future cancer treatment and mechanism exploration.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114773"},"PeriodicalIF":4.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247155","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":"2-Hydroxypropyl-β-cyclodextrin, solubiliser in a novel dantrolene formulation: Its binding affinities to clinical compounds that may be used during anaesthesia or management of malignant hyperthermia","authors":"Richard H. Ng Kwet Shing ,&nbsp;David J. Wright ,&nbsp;Sandeep Pal ,&nbsp;Samuel L. Smith ,&nbsp;Lucy B. Clayton ,&nbsp;Jonathan G. Bilmen","doi":"10.1016/j.ejpb.2025.114765","DOIUrl":"10.1016/j.ejpb.2025.114765","url":null,"abstract":"<div><div>2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) is used as an excipient to improve the solubility of the highly lipophilic drug dantrolene in a novel formulation, NPJ5008. Dantrolene acts as an antidote for life-threatening anaesthesia-associated malignant hyperthermia (MH) crises and intervention speed is essential to minimise morbidity. NPJ5008 can be prepared and administered substantially faster than DANTRIUM IV in a smaller volume of fluid. Like other cyclodextrins in clinical use, HP-β-CD forms inclusion complexes with lipophilic molecules. The potential of HP-β-CD to unintentionally interact <em>in vivo</em> with other drugs administered during anaesthesia or an MH emergency was assessed. An <em>in silico</em> predictive model of HP-β-CD binding was built from published data using LigPrep/Glide and GROMACS for molecular dynamic simulations to generate data for binding free energy calculations, performed with the molecular mechanics Poisson–Boltzmann surface area method using a thermodynamic cycle. Docking of &gt;70 anaesthesia-relevant compounds with HP-β-CD was evaluated and 10 compounds were predicted to bind HP-β-CD using a cut-off of −4 kcal mol⁻¹. <em>In vitro</em> isothermal titration calorimetry (37 °C, pH 7) was also used to determine the enthalpy of interaction of HP-β-CD with 18 of the most clinically relevant compounds, including rocuronium, vecuronium and remifentanyl (the strongest predicted binder from the <em>in silico</em> work). All had low injection heats with assay parameters of 1500 µM test compound and 50 µM HP-β-CD, i.e. there was no discernible binding to HP-β-CD. Thus, the HP-β-CD component of NPJ5008 is unlikely to interfere with other drugs clinically relevant in MH.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114765"},"PeriodicalIF":4.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247153","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":"FcRn-targeted Pluronic F127-Poly (L-lactic Acid) polymersomes for oral insulin delivery","authors":"Pin Pin Ma,&nbsp;Zi Ling Li,&nbsp;Hong Xia Gao,&nbsp;Xiang Yuan Xiong","doi":"10.1016/j.ejpb.2025.114761","DOIUrl":"10.1016/j.ejpb.2025.114761","url":null,"abstract":"<div><div>The intestinal epithelium barrier is one of the main factors limiting the bioavailability of oral insulin delivery systems. Neonatal Fc (fragment crystallizable) receptor (FcRn) is highly expressed in the intestinal epithelium, which can bind specifically to the Fc fragments of IgG in a pH-dependent manner and thus improve the transepithelial transport of carriers modified by IgG Fc or Fc domain-binding peptides (FcBP) ligand. Thus, FcBP ligand was attached to Pluronic F127-polylactic acid polymersomes by using the biotin-avidin bridging technology to obtain FcRn-targeted FcBP-F127-PLA polymersomes. Insulin (INS) was loaded successfully into FcBP-F127-PLA with the loading efficiency of 12.01 %. The transepithelial transport experiments on Caco-2 cells using Coumarin-6 (C-6) as a fluorescence probe showed that the cumulative permeability percentage and apparent permeability coefficient (Papp) of the<!--> <!-->FcBP-F127-PLA/C-6 group was 1.7 and 1.8 times that of PLA-F127-PLA/C-6 group after 2 h of incubation, respectively. FcBP ligand density of FcBP-F127-PLA played a role on their transepithelial transport ability and 10%FcBP-F127-PLA with 10 % FcBP molar content was found to be the best. The in vivo hypoglycemic results showed that the relative pharmacological bioavailability (PA_R%) of the<!--> <!-->oral 10%FcBP-F127-PLA/INS group was 43.6 %, which was 1.27 times that of the PLA-F127-PLA/INS group. Therefore, FcBP-F127-PLA polymersomes could be a promising carrier of the oral insulin delivery.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114761"},"PeriodicalIF":4.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144239906","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}