European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Impact of biological buffers and chelators on Fenton-like reactions in the context of poloxamer 188 degradation","authors":"Maksymilian M. Zegota ,&nbsp;Christian Schöneich ,&nbsp;Andrea Hawe","doi":"10.1016/j.ejpb.2025.114855","DOIUrl":"10.1016/j.ejpb.2025.114855","url":null,"abstract":"<div><div>Fenton-like reagents serve as useful tools to induce oxidative stress in forced degradation studies of surfactants, providing a relevant model due to the possible presence of trace amounts of transition metal ions and peroxides in liquid drug formulations. It is known that catalytic reactivity of transition metal ions heavily depends on the ligands present in the solution and that it differs between buffer systems. Herein, we compare the influence of common buffers and chelating agents on poloxamer<!--> <!-->188 (P188) degradation by using a fast-gradient reversed phase chromatography with charged aerosol detection (LC-CAD) and automatic sample preparation. These findings support root-cause analysis of P188 loss and provide insight into the reactivity of Fenton-like reagents in buffered systems.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114855"},"PeriodicalIF":4.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006090","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":"Long-term exposure in high viscous microenvironment facilitates acquired drug resistance of colon cancer cells to doxorubicin","authors":"Tianjiao Zeng ,&nbsp;Chengyu Lu ,&nbsp;Man Wang ,&nbsp;Huajian Chen ,&nbsp;Toru Yoshitomi ,&nbsp;Naoki Kawazoe ,&nbsp;Yingnan Yang ,&nbsp;Guoping Chen","doi":"10.1016/j.ejpb.2025.114852","DOIUrl":"10.1016/j.ejpb.2025.114852","url":null,"abstract":"<div><div>Chemotherapy is one of the most common strategies for treating colorectal cancer (CRC). However, acquired drug resistance (ADR) impairs the efficiency of chemotherapy. For CRC treatment, the long-term administration could affect cancer microenvironment and induce environment-mediated drug tolerance that contributes to ADR. Nevertheless, it is elusive that how the alteration of microenvironment affects the ADR of colon cancer cells. In this study, the effect of microenvironmental viscosity on ADR of colon cancer cells to doxorubicin (DOX) was investigated by long-term culture of colon cancer cells in different viscous media supplemented with DOX. The 50% inhibitory concentration (IC₅₀) value of drug-resistant cells established by culturing in high viscosity media was significantly higher than that of cells cultured in low viscosity media. The drug-resistant colon cancer cells established in high viscosity media exhibited higher expression levels of drug resistance-related genes (ABCC2 and ABCG2), higher migration ability and lower proliferation ability than the cells established in low viscosity medium. Long-term exposure in DOX-containing high viscosity media made the cells more tolerant to DOX and facilitated the ADR of colon cancer cells to DOX. The results disclosed the importance of microenvironmental viscosity on the ADR development and should provide useful information for cancer therapy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114852"},"PeriodicalIF":4.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997393","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":"Mechanistic insights into PS80 oxidative degradation in glass vials: Roles of critical factors (iron, histidine, aluminum, zinc) and their synergistic interactions","authors":"Zhuan Cheng ,&nbsp;Pengzhen Wang ,&nbsp;Xu Gao,&nbsp;Luting Liu,&nbsp;Quanmin Chen,&nbsp;Jeremy Guo","doi":"10.1016/j.ejpb.2025.114853","DOIUrl":"10.1016/j.ejpb.2025.114853","url":null,"abstract":"<div><div>Polysorbate 80 (PS80), a vital stabilizer in biotherapeutic formulations, faces persistent oxidative degradation challenges that threaten drug product stability during storage. While PS80 instability has been studied for decades, the oxidation mechanisms in specific formulation-packaging systems remain poorly understood. This work resolves this knowledge gap by demonstrating that PS80 oxidative degradation occurs exclusively in histidine-buffered formulations stored in glass vials. This phenomenon was found to be driven by four factors: iron (leaching from vials promoted by histidine), histidine, zinc (histidine-introduced) and aluminum (glass-derived). These four interdependent factors exhibited a unique functional synergy: 1) iron as the radical chain initiator; 2) histidine as a pro-oxidative cofactor lowering iron’s catalytic threshold via formation of an iron-histidine complex; 3) zinc and aluminum accelerate Fe²⁺/Fe³⁺ redox cycling through distinct potential-specific mechanisms, enhancing the overall catalytic efficiency. This study for the first time provides the systematic evidence of the histidine-glass system as an essential prerequisite for PS80 oxidation and reveals novel mechanistic insights on the interplay between formulation composition and packaging-derived contaminants. The findings establish a predictive framework to mitigate PS80 oxidative degradation, ultimately enhancing the stability and safety of protein therapeutics.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114853"},"PeriodicalIF":4.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000045","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":"Peptides as functional excipients for drug delivery","authors":"Takayuki Yoshida,&nbsp;Hiroyuki Kojima","doi":"10.1016/j.ejpb.2025.114856","DOIUrl":"10.1016/j.ejpb.2025.114856","url":null,"abstract":"<div><div>Peptides have a wide variety of amino acid compositions, sequences and conformations, which allow high specificity and great functionality. Biodegradable peptides arouse less concern about toxicity and tissue accumulation, while short peptides contribute to easy design and manufacturing, high quality, and low production costs. Thanks to these advantages, peptides can be used as high-functional excipients for drug delivery systems (DDS). Recent research has demonstrated the high performance of peptide excipients, including easy drug loading and sustained release of various drugs by self-assembling peptides, efficient cellular uptake/endosomal escape and higher transmucosal permeation by cell-penetrating peptides, and effective nanoparticle DDS for targeting cells and tissues using peptide ligands. Research progress has led to the approval of some new peptide excipients for clinical use, such as PuraStat and RTP004. In addition, green synthesis of peptides at low cost is also important for the use of peptides as excipients, and recent research will enable environmentally friendly solvents and purification. Further, given the importance of regulation to ensure the safety and quality of the new peptide excipients for broad use in many drug products, this review also summarizes current regulatory information on peptides and excipients.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114856"},"PeriodicalIF":4.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989304","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":"“ TPGS-Functionalized Nanocarriers with Improved Flavonoid Oral Bioavailability and Therapeutic Action: Pharmacokinetic and Mechanistic Insights in Diabetes-Induced Retinopathy ”","authors":"Maha Abdelmonem ,&nbsp;Asmaa K Al-Mokaddem ,&nbsp;Mohamed Y. Zakaria","doi":"10.1016/j.ejpb.2025.114851","DOIUrl":"10.1016/j.ejpb.2025.114851","url":null,"abstract":"<div><div>Diabetes mellitus is a metabolic disorder with escalating prevalence. It’s a chief cause of microvascular complications, notably diabetic retinopathy (DR), which can predispose to permanent vision loss. Inflammation and oxidative stress are pivotal contributors to the progression of DR. Luteolin (LUT), a naturally occurring flavonoid, possesses strong anti-inflammatory and antioxidant properties, offering therapeutic potential against DR. However, its clinical use is impeded by its restricted intestinal permeability and poor water solubility. In this study, twelve lipid–polymer hybrid nanoparticles (LPNPs) were developed using a 1³2² complete factorial design to explore the impact of three formulation variables: poly(ε-caprolactone) (PCL): d-alpha-Tocopheryl polyethylene glycol 1,000 succinate (TPGS) ratio (A), preparation technique (B) and phospholipid (PL) content (C). The optimized formulation (LP8), composed of 50 mg of phospholipid, PC: TPGS (2:1) and prepared via the emulsion solvent evaporation method, demonstrated a high zeta potential (−34.9 ± 5.2  mV), a small particle size (215.3 ± 10.3  nm), and a high entrapment efficiency (93.1 ± 2.4 %). Compared to LUT suspension, LP8 demonstrated prolonged in vitro drug release and markedly enhanced ex vivo intestinal permeability. In streptozotocin (STZ)-induced diabetes, LP8 resulted in significant reduction in hyperglycemia, retinal inflammation, oxidative stress and angiogenesis while preserving retinal structure. Moreover, LP8 significantly downregulated the expression of MDA, IL-1β, NLRP3, ASC, and VEGF while upregulated GSH and Nrf2 levels in the retina. Additionally, pharmacokinetic study confirmed a substantial improvement in oral bioavailability of LUT-loaded LP8 compared to LUT-suspension. These findings proposed that the optimized LUT-loaded LPNPs represent a potential oral nanoplatform for the effective management of DR.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114851"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991882","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":"Design of peptide functionalized nitrogen doped graphene quantum dots for theranostic application in breast cancer","authors":"Vrushti Kansara,&nbsp;Mitali Patel","doi":"10.1016/j.ejpb.2025.114842","DOIUrl":"10.1016/j.ejpb.2025.114842","url":null,"abstract":"<div><div>The nitrogen doped graphene quantum dots (N-GQDs) were functionalized for active targeting of epidermal growth factor receptor (EGFR) overexpressed breast cancer cells for the delivery of palbociclib (PLB). The N-GQDs were covalently conjugated with a dodecapeptide, GE11 (YHWYGYTPQNVI), a ligand with high affinity for EGFR and then loaded with PLB. The resulting PLB loaded N-GQDs (PLB-N-GQDs) and GE11-N-GQDs (GE11-PLB-N-GQDs) exhibited particle size of 85.25 ± 1.65 nm and 115.1 ± 2.47 nm, respectively. The surface functionalization of GE11 was confirmed by amide bond formation. The high-resolution transmission electron microscopy study revealed structural distortion in the GE11-PLB-N-GQDs due to functionalization and drug loading. The formulations were hemocompatible and hence were suitable for direct administration. The GE11-PLB-N-GQDs showed significantly higher release at pH 5.5 than pH 6.8 and pH 7.4. The confocal microscopy displayed the use of inherent fluorescence of the N-GQDs and GE11-N-GQDs across MCF-7 cells indicating their potential for bioimaging. The increased cellular uptake of the GE11-N-GQDs demonstrated effective EGFR targeting which increased cytotoxicity by the GE11-PLB-N-GQDs as compared to the PLB-N-GQDs. The GE11-PLB-N-GQDs induced G1 phase cell cycle arrest and apoptosis. This study demonstrates the potential of GE11-N-GQDs as a versatile theranostic nanocarrier for targeted delivery to breast cancer cells overexpressing EGFR.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114842"},"PeriodicalIF":4.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920090","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":"Comparison of dissolution profiles: 90 % confidence intervals of different f2 estimators using bootstrap methodology versus the Euclidean Distance of the Non-standardized Expected (EDNE) values","authors":"Zhengguo Xu ,&nbsp;Marina Cuquerella-Gilabert ,&nbsp;Javier Zarzoso-Foj ,&nbsp;Matilde Merino-Sanjuan ,&nbsp;Victor Mangas-Sanjuan ,&nbsp;Alfredo García-Arieta","doi":"10.1016/j.ejpb.2025.114839","DOIUrl":"10.1016/j.ejpb.2025.114839","url":null,"abstract":"<div><div>The most widely used method to compare dissolution profiles is the similarity factor <span><math><msub><mrow><mi>f</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span> method. When the regulatory requirements to apply the <span><math><msub><mrow><mi>f</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span> method are not fulfilled, alternative methods should be used. In the current study two commonly used methods, 90<!--> <!-->% confidence intervals (CI) of different <span><math><msub><mrow><mi>f</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span> estimators using bootstrap methodology and the Euclidean Distance of the Non-standardized Expected (EDNE) values, are compared using two different simulation approaches. For the first approach, the reference and test population profiles were simulated based on the multivariate normal distribution with different target population <span><math><msub><mrow><mi>f</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span> values, variability, and sample sizes. For each pair of randomly simulated profiles, 90<!--> <!-->% CI of various <span><math><msub><mrow><mi>f</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span> estimators and the EDNE values were calculated. For the second approach, the first-order release model-based simulation, one million individual dissolution profiles were simulated for the reference and test populations with different variability and predefined target population <span><math><msub><mrow><mi>f</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span> values, random samples of different sizes were taken from those populations to obtain 90<!--> <!-->% CI of the same <span><math><msub><mrow><mi>f</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span> estimators and the EDNE values. The whole process was repeated 10<!--> <!-->000 times for both approaches to evaluate the type I error and statistical power of the methods by calculating the percentages of replicates where the dissolution profiles are similar. When the true populations of test and reference profiles are not similar, this percentage of similarity represents the type I error; when the true populations of test and reference profiles are similar, this percentage represents the statistical power. The results shows that the EDNE method has much higher statistical power than the bootstrap <span><math><msub><mrow><mi>f</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span> methods, but the associated type I errors are also unacceptably higher, making it unsuitable for regulatory adoption. The best method is the 90<!--> <!-->% CI of the expected <span><math><msub><mrow><mi>f</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span>, therefore, this method is recommended. In addition, sample sizes should be increased to account for the low statistical power when using bootstrap methods.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114839"},"PeriodicalIF":4.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946495","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":"Carrier free nano-assembled redox dual-responsive biotin-artesunate conjugate for enhanced tumor therapy","authors":"Jiabao Liu ,&nbsp;Ke Mei ,&nbsp;Xiaoshuang Dai ,&nbsp;Yang Song ,&nbsp;Lian Deng ,&nbsp;Jianpeng Liu ,&nbsp;Junda Liu ,&nbsp;Neng Qiu","doi":"10.1016/j.ejpb.2025.114841","DOIUrl":"10.1016/j.ejpb.2025.114841","url":null,"abstract":"<div><div>Artesunate (ART) exhibits anti-tumor activity, however, its clinical application has been hindered due to its insufficient tumor selectivity and undesired toxicity to normal tissues. To improve its tumor selectivity, ART was conjugated with biotin through disulfide bond to produce Bio-SS-ART. The Bio-SS-ART could self-assemble into spherical nanoparticles in aqueous solution with particles size of 158.6 nm. <em>In vitro</em> release studies revealed that Bio-SS-ART exhibited accelerated release in reductive environment and released much faster in PBS than in water in the presence of GSH or DTT. Moreover, Bio-SS-ART also showed quick release in oxidative environment. Cell uptake studies showed that the fluorescence intensity of Rhodamine B (RhB) loaded Bio-SS-ART NPs exhibited 3.92-fold enhancement compared to that of free RhB. The inhibition of biotin significantly reduced the cellular uptake of RhB loaded Bio-SS-ART NPs and 7-hydroxycoumarin-labeled biotin (Bio-7-Hy) in a concentration and time-dependent manner. Multiple endocytotic pathways were included in the internalization of the biotinylated prodrug and nanomedicine. <em>In vitro</em> studies showed that the cytotoxicities of Bio-SS-ART and Bio-SS-ART NPs were 11.85-fold and 3.81-fold of that of ART against biotin receptor positive MCF-7 cells. In addition, the introduction of disulfide bond in biotinylated ART prodrugs exhibited higher anticancer activity than that of alkyl chain conjugated prodrug. Therefore, the biotinylation and introduction of disulfide bond could enhance the tumor targeting and anticancer activity of ART. Our study might provide a new strategy in designing highly efficient intracellular drug delivery and controlled drug release for future cancer treatment.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114841"},"PeriodicalIF":4.3,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892139","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":"Novel electrosprayed core-shell polyethyleneimine and phospholipid coated MSNs for Co-delivery of KAZ3 and MDR-1 siRNA for efficient chemotherapy in multidrug-resistant colon cancer","authors":"Elshaimaa Sayed ,&nbsp;Ketan Ruparelia ,&nbsp;Saman Zafar ,&nbsp;Ahmed Faheem ,&nbsp;Dimitris Fatouros ,&nbsp;Muhammad Sohail Arshad ,&nbsp;Neenu Singh ,&nbsp;Zeeshan Ahmad","doi":"10.1016/j.ejpb.2025.114838","DOIUrl":"10.1016/j.ejpb.2025.114838","url":null,"abstract":"<div><div>Different strategies and multifunctional nano-carriers have been employed to enhance chemotherapeutic drugs bioavailability and tackle acquired multi-drug resistance (MDR) thus ensuring efficient chemotherapy with fewer adverse effects. Among these, mesoporous Silica Nanoparticles (MSNs) are exciting matrices for improving cytotoxic drugs bioavailability and circumventing MDR through its potential of co-delivery of anticancer agents and short interfering RNA (siRNA).</div><div>In this study, MSNs were coated with (1:1) Polyethyleneimine (PEI) and phospholipids (PL) composite and were loaded with KAZ3 (Anticancer chalcone) using coaxial electrospraying in a one step process. The novel delivery system was used to co-deliver both MDR-1 siRNA and KAZ3 to colon cancer cell lines in order to knockdown the MDR-1 gene and thus to improve KAZ3 cytotoxicity. The prepared drug/siRNA delivery system was characterized using SEM, fluorescence microscopy, TGA, zeta sizer, actives (KAZ3 and siRNA) loading efficiency, actives release studies, siRNA gel retardation and actives cellular uptake. The cytotoxicity of formulations against cancer cell lines (HCT 116) was also assessed using MTT assay and MDR-1 gene silencing efficiency using western blotting. Results showed that coaxial electrospraying was efficient in preparing core–shell coated MSNs that were able to co-deliver both MDR-1 siRNA and KAZ3 to colon cancer lines. The MSNs coated with PL and 2.5 KDa PEI were found to be more compatible with human cells than to 25KDa PEI coated MSNs. KAZ3/siRNA loaded PEI-PL coated MSNs were successful in decreasing multidrug resistance gene expression to 40 % and causing up to 92 % colon cancer cell death. The findings of the present study show the immense potential of electro-hydrodynamic atomization (EHDA) as a technique for producing drug loaded MSNs based core–shell particles.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114838"},"PeriodicalIF":4.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859013","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":"Molecular effects of paclitaxel-elacridar nanoemulsions in breast cancer cells: impact on uptake, cell cycle and signaling pathways","authors":"Giovanna C. Salata,&nbsp;Isabella D. Malagó,&nbsp;Giovanna Barros de Melo,&nbsp;João Agostinho Machado-Neto,&nbsp;Luciana B. Lopes","doi":"10.1016/j.ejpb.2025.114837","DOIUrl":"10.1016/j.ejpb.2025.114837","url":null,"abstract":"<div><div>In this study, we investigated how paclitaxel incorporation in a bioadhesive, hyaluronic acid-modified nanoemulsion (NE) containing the P-glycoprotein inhibitor elacridar influenced its molecular effects and mechanism of action in breast cancer cells. Incorporation of paclitaxel with elacridar in the nanoemulsion resulted in a 2.5-fold increase in cellular uptake compared to the drug solution. Clathrin-mediated endocytosis contributed to nanoemulsion-mediated cell internalization, with both paclitaxel and NBD-phosphatidylcholine (nanoemulsion surfactant) partially co-localizing with transferrin. The nanoemulsion amplified paclitaxel-mediated chromatin condensation and expression of proteins involved in apoptosis, with a 2.5-fold increase in PARP1 (Poly (ADP-ribose) polymerase 1) cleavage and a 1.7-fold downregulation of BCL2 (B-cell lymphoma protein 2) expression. Apoptosis was maintained as the main mechanism of cell death. The formulation also reduced cell migration (3-fold) compared to the solution at concentrations lower than IC₅₀, while the clonogenic effect (17-fold) was not hindered, supporting a broader impact on tumorigenesis.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114837"},"PeriodicalIF":4.3,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820971","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}