International Journal of Pharmaceutics最新文献

{"title":"Thermo-responsive mucoadhesive in-situ gelling system loaded with surface-engineered PLGA nanoparticles for sustained intravaginal delivery of efavirenz in HIV pre-exposure prophylaxis","authors":"Avichal Kumar ,&nbsp;H.N. Shivakumar ,&nbsp;Dhruti Avlani ,&nbsp;Sumit Dhiman","doi":"10.1016/j.ijpharm.2025.126262","DOIUrl":"10.1016/j.ijpharm.2025.126262","url":null,"abstract":"<div><div>HIV remains incurable, severely compromising the immune system. This study presents a surface-engineered, biocompatible nanoparticle-in-gel system for localized intravaginal delivery of Efavirenz (EFZ) in HIV PrEP. EFZ, a BCS Class II NNRTI, was efficiently encapsulated into Pluronic F-127 coated PLGA (50:50) nanoparticles (EFZ-PLGA NPs) using a modified emulsion solvent evaporation method optimized employing Box-Behnken design. Optimization of the process resulted in EFZ-PLGA NPs with an average size of 144.3 ± 2.13 nm, ζ-potential of −17.52 ± 0.78 mV, PDI of 0.248 ± 0.14 and entrapment efficiency of 87.00 ± 1.37 %. The surface energy (87.4 ± 1.17mN/m) indicated enhanced wettability, which would favour bioadhesion. AFM and SEM confirmed smooth, discrete and spherical shape of NPs while FTIR confirmed the chemical integrity of drug in NPs. DSC, and PXRD confirmed the amorphous state of FEZ in the polymer matrix. The nanoparticle-loaded gel displayed sol–gel transition at 38 ± 2.2 °C, gelation in 57 ± 2.1sec, viscosity of 13,857 ± 172.75 mPa·s (37 ± 0.5 °C) and sustained release (69.21 ± 2.38 % in 12 hrs). MTT assay indicated the reduced cytotoxicity of NPs. Pharmacokinetics revealed significantly (P &lt; 0.0001) higher vaginal EFZ levels (C_max: 18,309 ± 475 ng/mL) than that noted in plasma (C_max: 59.7 ± 6 ng/mL), with 3-fold higher concentration in lower uterus (110.41 ± 7.98 ng/mL) as compared to upper (33.26 ± 3.82 ng/mL) and middle (25.23 ± 9.65 ng/mL) uterus, that exceeded the IC₅₀ of EFZ (∼0.442–0.82 ng/mL). Histopathology confirmed biocompatibility, and safety of intravaginal formulations. This study demonstrates strong translational potential of the nanoparticle-in-gel platform that enables localized, sustained delivery of EFZ for intravaginal HIV PrEP. The favourable pharmacokinetics, safety profile, and bioadhesive properties of the drug delivery platform highlight its promise for clinical advancement in female-controlled HIV prevention strategies.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126262"},"PeriodicalIF":5.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258194","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":"Lyophilized Listeria monocytogenes vaccines for storage at non-ultra-low temperatures and cancer therapy.","authors":"Wyatt Paulishak, Larry Isenhower, Shadan Modaresahmadi, Sahelosadat Hajimirzaei, Jackson Shoultz, Laurence M Wood","doi":"10.1016/j.ijpharm.2025.126239","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.126239","url":null,"abstract":"<p><p>Lyophilization is a common method of preparing bacteria for storage with lyoprotectant and buffer greatly impacting viability. Listeria monocytogenes (LM) is a Gram-positive intracellular bacterium being investigated preclinically and clinically as an anticancer vaccine platform and is stored at ultra-low temperatures (ULT). ULT storage limits LM therapy accessibility due to a lack of necessary storage equipment in many areas of the world. Here, we show lyophilization of LM maintains viability and efficacy of LM anticancer vaccines in a murine subcutaneous renal cell carcinoma model. Through development of lyophilization media, we found that the choice of lyoprotectant and buffer dramatically impacts LM viability following lyophilization and during storage. Of those tested, the HEPES 2.5 % sucrose medium (3 mM HEPES 2.5 % w/v sucrose) demonstrated the best viability while maintaining the infectivity and antitumor efficacy of LM in a subcutaneous renal cell carcinoma model. The methods described herein are easily adoptable for the preparation of LM and stable storage at non-ultra-low temperatures.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126239"},"PeriodicalIF":5.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274514","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":"Spray freeze-dried doxycycline nanoparticles for macrophage-targeted lung delivery.","authors":"Manar Magdy, Hugh D C Smyth, Azza A Mahmoud, Nermeen A Elkasabgy, Sally A Mohamed, Arifenur Safak, Amr Maged","doi":"10.1016/j.ijpharm.2025.126246","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.126246","url":null,"abstract":"<p><p>Developing inhalable drug delivery systems offers transformative potential for treating lung diseases by enabling localized, efficient, and sustained therapeutic effects. In this study, doxycycline was encapsulated into lipid nanoparticles (LNPs) composed of different percentage molar ratios of L-α-egg phosphatidylglycerol (EPG) or 1,2-di(cis-9-octadecenoyl)-sn-glycerol 3-phosphate sodium salt (DOPA) with L-α-hydrogenated soybean phosphatidylcholine (HSPC), and cholesterol (CHO), using a microfluidics method to enhance its bioavailability and therapeutic efficacy. LNPs were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), drug content, and in-vitro drug release. LNPs containing DOPA, HSPC, and CHO in a percentage molar ratio of 60:20:20 exhibited a smaller PDI, and the highest drug content (∼95 %), and were subsequently processed into a dry powder inhalation (DPI) formulation via spray freeze-drying (SFD) using mannitol, mannose, and leucine, exhibiting suitability for pulmonary administration. Next-generation impactor (NGI) aerosol dispersions studies confirmed suitable aerosolization properties for lung targeting with a mass median aerodynamic diameter (MMAD) adequate for deposition in the lower respiratory tract. The DPI formulation also exhibited efficient cellular uptake and targeting of J774.A1 macrophage cells, resulting in superior antimicrobial efficacy within macrophages. This formulation provides a promising inhalable drug delivery system for doxycycline loaded LNPs for targeting alveolar macrophages to boost antimicrobial activity against critical lung infection.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126246"},"PeriodicalIF":5.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274530","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":"Direct compression peptide tablets: insights into the importance of permeation enhancer processibility and peptide stability.","authors":"A Fagan, L M Bateman, M O'Mahony, A M Crean, J P O'Shea","doi":"10.1016/j.ijpharm.2025.126257","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.126257","url":null,"abstract":"<p><p>Much of the remarkable advancements in oral peptide delivery have been achieved through the use of chemical permeation enhancers, such as sodium caprate (C10) and salcaprozate sodium (SNAC). However, co-formulation of peptides with permeation enhancers in an oral product introduces several processing and formulation challenges which require further investigation. This investigation sought to rationalise the development of direct compression insulin compacts, using C10 and SNAC as model permeation enhancers, respectively. The physical and mechanical properties of C10 and SNAC were first assessed to evaluate their suitability for processing via direct compression. Overall, C10 displayed passable flow character, however, poor tabletability, compactibility and compressibility profiles were obtained. SNAC, on the other hand, exhibited superior compaction properties, though its flow character was poor. Improvement in the compaction properties of both materials were observed on addition of commonly used direct compression excipients microcrystalline cellulose (MCC) and polyvinylpyrrolidone (PVP) K30, and formulations consisting of 72 % C10/ SNAC, 20 % MCC, 5 % PVP and 3 % insulin were selected for production of direct compression compacts at compaction pressures of 100 and 200 MPa. The compacts produced exhibited complete release within 30 min, and this release behaviour was not significantly affected by the compaction pressure used. Furthermore, the stability of insulin after compaction at 200 MPa, and on storage of the compacts at 40 °C/ 75 % RH for 1 month was assessed. Insulin displayed excellent physical stability to mechanical stress, where no evidence of unfolding or aggregation was identified. Moreover, on storage of the formulations at accelerated stability conditions for 1 month, a significant reduction in overall deamidation and aggregation tendency was observed on blending of insulin within the direct compression formulations in comparison to raw insulin material stored under the same conditions, independent of the permeation enhancer used. These results offer a key insight into the influence that formulation components have on the manufacturability of direct compression peptide formulations and the stability of the peptide during compaction and storage.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126257"},"PeriodicalIF":5.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274417","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":"Innovative scaffold design in biomedical: a comprehensive review of biomaterial integration and 3D printing techniques with emphasis on fused filament fabrication.","authors":"Aman Kumar, Cheshta, Avinash, Tasaduq Hussain Mir, M Mursaleen, M A Shah","doi":"10.1016/j.ijpharm.2025.126250","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.126250","url":null,"abstract":"<p><p>This review study looks at the design of Fused Filament Fabrication (FFF) scaffolds for tissue engineering, emphasizing their significance as supporting structures for tissue regeneration. Scaffolds are seeded with cells or other materials and implanted to promote tissue growth in tissue engineering. The study focuses on how sophisticated scaffolds with precise mechanical properties and improved cell compatibility can be fabricated using advanced additive manufacturing (AM) techniques such stereolithography (SLA), selective laser sintering (SLS), low-temperature deposition like digital layer processing (DLP), and FFF. These developments have a major positive impact on the healthcare industry since 3D printing allows for the customisation of medical devices including implants, surgical equipment, and prosthetics, which lowers recuperation periods and enhances therapeutic results. This research examines the integration of different biomaterials and techniques to enhance the mechanical characteristics and porosity of scaffolds, with a specific focus on the usage of FFF in biomedical applications. This paper offers insights into how FFF can be used to create efficient tissue engineering solutions, which is a useful tool for improving scaffold design in biomedical research and applications.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126250"},"PeriodicalIF":5.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274509","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":"Dual-drug thermosensitive hydrogel-based microneedles for synchronized transdermal delivery of paeoniflorin and glycyrrhizic acid.","authors":"Yuwei Shi, Xianwei Zhu, Yingying Yu, Wei Jiao, Chen Chen, Xiaocen Wei, Lei Shi, Yuxia Ma, Mengzhen Xing, Yuning Ma, Yunhua Gao","doi":"10.1016/j.ijpharm.2025.126237","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.126237","url":null,"abstract":"<p><p>Efficient and synchronized co-delivery of active pharmaceutical ingredients (APIs) from classical Traditional Chinese Medicine (TCM) formulae is crucial for exerting their synergistic therapeutic effects. However, constructing dual-drug-loaded systems capable of controllably delivering APIs with divergent polarities remains challenging due to differences in molecular weight and solubility among constituents. In this study, paconiflorin (PAE) and glycyrrhizic acid (GLA)-active ingredients derived from the renowned TCM formula Shaoyao Gancao Decoction-were selected as model compounds. To address the co-loading and synchronized delivery of hydrophilic PAE and hydrophobic GLA, we developed a β-glycerophosphate disodium salt (β-GP)/hydroxypropyl cellulose (HPC) hydrogel. This hydrogel uniquely combined skin-triggered sol-gel transition with electrostatically enhanced solubility for GLA, and was subsequently fabricated into a microneedles (MNs) formulation. Confocal laser scanning microscopy confirmed uniform distribution of both drugs within the MNs, despite their contrasting polarities. In vitro transdermal studies revealed that the MNs significantly outperformed the hydrogel in terms of delivery efficiency. Release kinetics followed the Higuchi model, with cumulative release rates at 72 h reaching 38.84 ± 0.52 % for PAE and 44.26 ± 4.38 % for GLA, indicating synchronized release. This platform represents an innovative strategy for achieving the synchronized, efficient, and sustained delivery, holding significant promise for advancing the development of TCM formulations.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126237"},"PeriodicalIF":5.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274463","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":"Ibrutinib-loaded lipid nanocarriers exhibit antitumor effect in a human ex vivo skin model of melanoma.","authors":"Maria Victoria Souto-Silva, Naomi Souza Rodrigues, Lucas F F Albuquerque, Jankerle Neves Boeloni, Eliza Carla Barroso Duarte, Mayra Oliveira-Mendes, Carolina Souto-Rocha, Stefhani Barcelos, Emãnuella Melgaço Garcez, Amandda Evelin Silva-Carvalho, Florêncio Figueiredo Cavalcanti Neto, Guilherme M Gelfuso, Felipe Saldanha-Araujo, Juliana Lott Carvalho","doi":"10.1016/j.ijpharm.2025.126249","DOIUrl":"10.1016/j.ijpharm.2025.126249","url":null,"abstract":"<p><p>Cutaneous melanoma is an aggressive skin cancer with high metastatic potential and frequent resistance to apoptosis-inducing therapies. Ibrutinib (IBR), a Bruton's tyrosine kinase inhibitor, has demonstrated antitumor potential, yet its topical application is not well established. This study evaluated the cytotoxic, antiproliferative, and skin permeation effects of free IBR and IBR-loaded nanostructured lipid carriers (IBR + NLC) using human melanoma cells (SK-MEL-28) and ex vivo human skin models. NLC + IBR presented enhanced toxicity towards melanoma cells by promoting necroptosis, as evidenced by the absence of caspase-3/7 activation, increased expression of RIPK1 and RIPK3, elevated LDH release, and plasma membrane disruption. In addition, mitochondrial depolarization was observed, likely as a consequence of necroptotic signaling and associated cellular stress. NLC + IBR significantly enhanced reactive oxygen species production, induced cell cycle arrest in the sub-G1 phase, and reduced CDK1 and CDK2 gene expression. Clonogenic and migration assays confirmed complete suppression of tumor cell colony formation and reduced migratory capacity following NLC + IBR treatment. Skin permeation studies revealed that NLC + IBR enabled deeper drug skin penetration, with reduced retention in the stratum corneum and higher accumulation in the viable skin layers, the primary therapeutic target in cutaneous melanoma. Finally, using an ex vivo human skin model of melanoma, NLC + IBR promoted melanoma cell necrosis, while maintaining a favorable topical safety profile with no significant irritation. These findings suggest that NLC + IBR topical application is a promising strategy for localized treatment of cutaneous melanoma, particularly in early-stage or adjuvant contexts.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126249"},"PeriodicalIF":5.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274555","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 novel peptide excipient stabilizes DaxibotulinumtoxinA.","authors":"Shaoqiu Zhuo, G Reza Malmirchegini, Conor J Gallagher","doi":"10.1016/j.ijpharm.2025.126238","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.126238","url":null,"abstract":"<p><p>Surface adsorption of proteins in bulk drug product formulations and loss of protein structural integrity during manufacturing processes can diminish drug potency. In formulations containing low biologic drug substance, such as botulinum toxin type A (BoNTA) products, loss of active protein is a major concern. To mitigate the risk of activity loss, most commercial BoNTA products contain an abundance of human serum albumin (HSA, 125-1000 µg/vial) to prevent adsorption of BoNTA to container surfaces by competing for nonspecific binding sites. The stabilizing ability of HSA is well established; however, there are notable potential safety concerns surrounding its use as an excipient. Our data suggests that at pH 5.5, in the presence of increasing concentrations of HSA the 150 kDa BoNTA core neurotoxin (RTT150) may form aggregate complexes with HSA when heated to 45-50 °C, in a dose-dependent manner. A new BoNTA product has recently been approved with a unique formulation which uses a proprietary synthetic cationic peptide (RTP004) to replace HSA as a stabilizer. Here, we show that RTP004 binds to the core neurotoxin and enhances its thermostability. In combination with polysorbate 20 (PS20), RTP004 efficiently and completely prevents surface adsorption of the 150 kDa core neurotoxin and stabilizes the biologic drug substance during manufacturing processes, even at concentrations 10- to 100-fold less than those used for HSA in commercial BoNTA products. Thus, the combination of RTP004 and PS20 forms the basis for a novel and effective BoNTA formulation, removing the need for HSA and thereby avoiding its theoretical safety risks and documented limitations.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126238"},"PeriodicalIF":5.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274434","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 cholesteric liquid crystal and xerogel of clarithromycin-ascorbic acid with enhanced antimicrobial and antibiofilm activity","authors":"Antonela Bartolilla ,&nbsp;Ariana Zoppi ,&nbsp;Marcela R. Longhi ,&nbsp;Virginia Aiassa","doi":"10.1016/j.ijpharm.2025.126255","DOIUrl":"10.1016/j.ijpharm.2025.126255","url":null,"abstract":"<div><div>Antimicrobial resistance represents a worldwide problem that necessitates the creation of innovative pharmaceutical strategies. In this study, two carrier-free supramolecular systems composed exclusively of clarithromycin (CTY) and ascorbic acid (AA) were developed and characterized: a semi-solid amphotropic cholesteric liquid crystal (CLC) and a xerogel. The CLC gel represents the first report of a spontaneous and stable formation of a cholesteric phase from an antibiotic without additional structuring agents. Rheological studies and polarized light microscopy (PLM) show that the mesophase displayed typical viscoelastic behavior with both lyotropic and thermotropic features and consisted of nanometric particles with moderate uniformity, as confirmed by dynamic light scattering (DLS). The system enhanced the antibacterial activity of CTY. This was reflected in a lower minimum inhibitory concentration (MIC) and in the inhibition of <em>Staphylococcus aureus</em> biofilms, including clinical isolates. These findings highlight its potential use in topical or oral antibiotic formulations. The xerogel showed a lamellar organization, as revealed by the calculation of interplanar distances from the X-ray diffraction pattern and further supported by scanning electron microscopy (SEM). This system offers a novel and simple platform for the formulation of antibiotics.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126255"},"PeriodicalIF":5.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270308","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":"Impact of methotrexate-loaded fattigated albumin nanoparticles and pharmaceutical excipients on real-time reactive oxygen species and cell viability in a microfluidic chip system.","authors":"Sura Saad Abdullah, Eun-Ji Kim, Jeongro Lee, Hy Dinh Nguyen, Beom-Jin Lee","doi":"10.1016/j.ijpharm.2025.126259","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.126259","url":null,"abstract":"<p><p>This study examined the impact of methotrexate (MTX)-loaded albumin-oleic acid nanoparticles (MTX-AONs) and pharmaceutical excipients (PEs) on cell viability and real-time reactive oxygen species (ROS) sensing in breast cancer cells (MCF-7) and human non-tumorigenic breast epithelial cells (MCF-10A). Water-soluble PEs, such as sodium dodecyl sulfate (SLS), D-α-tocopheryl polyethylene glycol 1000 succinate (D-α-TPGS), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), and sodium oleate (SO), were also screened for their ability to improve MTX solubility and influence cellular responses. The self-assembled albumin-oleic acid nanoparticles (AONs) prepared by desolvation, exhibited a mean particle size of 184 ± 2 nm, polydispersity index (PDI) of 0.23 ± 0.01, and zeta potential of -37.07 ± 0.9. MTX loading yielded an encapsulation efficiency of 93 % and loading of 9.3 %, increasing particle size greatly to 306.8 ± 2 nm with minimal changes in PDI (0.15 ± 0.01) and zeta potential (-30.3 ± 0.6). The PEs (1 %, w/w) influenced aqueous MTX solubility (mg/mL), giving in the order: SO (5.89 ± 0.12), SLS (1.52 ± 0.11), HP-β-CD (0.97 ± 0.03) and D-α-TPGS (0.64 ± 0.03) compared with free MTX (0.58 ± 0.04 mg/mL). Under dynamic shear stress, MTX-AONs exhibited enhanced anticancer activity compared with static conditions. Furthermore, MCF-7 cell viability was decreased in a dose-dependent manner, while MCF-10A cells were spared, suggesting better cellular uptake than that of free MTX. Co-treatment with PEs decreases MCF-7 cell viability; however, their effectiveness is not affected by MTX solubility. For example, SLS and D-α-TPGS combined with MTX-AONs showed the strongest effects on the cellular viability of MCF-7 cells in both static and dynamic environments, while maintaining MCF-10A cells. As the drug concentration increased, cell viability decreased accordingly, whereas real-time ROS production increased, indicating a good correlation. Interestingly, the expected lethal dose (LD₅₀) calculated from the half-maximal inhibitory concentration (IC₅₀) correlated with the reported LD₅₀ of MTX. The microfluidic chip system can be utilized to screen the impact of formulation design and PEs in cancer therapy by simultaneously measuring cellular viability and real-time ROS levels to predict clinical relevance.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126259"},"PeriodicalIF":5.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258220","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}