European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Factors affecting flash nanoprecipitation of Pharmaceuticals: Principles and applications","authors":"Wisdom Awuku,&nbsp;Bi-Botti Celestin Youan","doi":"10.1016/j.ejpb.2026.114984","DOIUrl":"10.1016/j.ejpb.2026.114984","url":null,"abstract":"<div><div>Flash nanoprecipitation (FNP) has emerged as a transformative technique in the preparation of nanoparticles for targeted drug delivery. Traditional drug delivery systems often struggle with challenges such as poor solubility, limited bioavailability, and suboptimal targeting. FNP addresses these limitations through a one-step, scalable process that produces nanoparticles with tunable size, composition, morphology, and surface characteristics. This review explores the principles of FNP, focusing on its application in encapsulating bioactive agents, achieving controlled release, and enhancing bioavailability. Unlike conventional emulsification or antisolvent precipitation methods, FNP utilizes rapid mixing under kinetically controlled conditions to achieve high reproducibility and uniform particle distribution. The technique has been successfully employed for various pharmaceutical applications, including the delivery of small molecules, biologics, and nucleic acids. Beyond laboratory research, FNP has been adopted in industrial and clinical settings—for instance, in the scalable production of lipid nanoparticles (LNPs) for mRNA-based vaccines and other nucleic acid therapeutics—demonstrating its translational potential. Furthermore, its adaptability extends to theranostic and imaging applications. The review highlights critical formulation variables and process parameters, such as polymer type and its glass transition temperature, solvent selection, and Reynolds number, which influence key characteristics such as nanoparticle stability and performance. By synthesizing recent advances, this paper provides a comprehensive overview of how FNP is already transforming drug delivery, highlighting its current impact, and future research directions.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"221 ","pages":"Article 114984"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942989","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":"Rifampicin-containing interpenetrating hydrogel networks (IHNs) based on poly(methacrylates) and Poloxamers, and their potential as short-duration use antimicrobial medical device biomaterials","authors":"David S. Jones,&nbsp;M. Westwood,&nbsp;S. Li,&nbsp;Gavin P. Andrews","doi":"10.1016/j.ejpb.2026.114987","DOIUrl":"10.1016/j.ejpb.2026.114987","url":null,"abstract":"<div><div>This study describes the surface, mechanical, swelling, microbial anti-adherence and drug release properties of rifampicin-containing interpenetrating hydrogel networks (IHNs) composed of either poly(hydroxyethylmethacrylate, p(HEMA)) or poly(methacrylic acid, p(MAA)) and Poloxamer block copolymers (grades F127, P123 and L121), prepared using free radical polymerisation and designed as coatings for urinary medical devices. The swelling and mechanical properties of the IHNs were affected by the polymethacrylate type, Poloxamer grade and concentration. Incorporation of Poloxamers decreased the crosslink density and increased the pore size of the hydrogels at pH 7.2 (calculated from swelling data), leading to enhanced IHN swelling and reduced ultimate tensile strength and Young’s <em>Modulus</em>. The static contact angles of the IHNs depended on the type of polymethacrylate but not on the Poloxamer grade/concentration. In particular, the contact angles of p(HEMA) IHNs were greater than for p(MAA) IHNs. The contact angles of p(MAA) IHNs at pH 4 were greater than those at pH 7.2. ATR-FTIR confirmed the presence of PEO at the surface of p(MAA)/F127 IHNs. Drug loading into (by swelling) and subsequent release at pH 7.2 buffer depended on polymethacrylate type, grade and concentration of Poloxamers. Rifampicin release from p(MAA) IHNs was significantly greater than from comparator p(HEMA) IHNs, due to both the greater loading of rifampicin and the increased pore size of these hydrogels. The mass of rifampicin loaded into the hydrogels was greater for p(MAA) IHNs Release of rifampicin from p(MAA) hydrogels at pH 4 (pre-swollen in rifampicin solutions at pH 7.2) involved burst release (dependent on and reduced by increasing concentration of Poloxamer), followed by slow, controlled release, again affected by Poloxamer concentration. p(HEMA) p(HEMA) IHNs significantly decreased microbial adherence, with the inclusion of rifampicin inhibiting microbial adherence at 4 h (for selected IHNs) and 24 h. Microbial adherence to rifampicin-containing p(MAA) IHNs following a 4-hour contact time was inhibited; however, given the rapid drug release, prolonged anti-adherence is unlikely. Conversely, the ability of Poloxamers to enhance and offer both greater control of rifampicin release from p(HEMA) IHNs and the more prolonged anti-adherence effects make these platforms more suitable for urinary application.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"221 ","pages":"Article 114987"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948505","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 refined coadministration regime to mitigate immunological clearance of biomedical nanoparticles","authors":"Kathrin Schorr,&nbsp;Johannes Konrad,&nbsp;Jan Birringer,&nbsp;Carsten Damm,&nbsp;Miriam Breunig,&nbsp;Achim Goepferich","doi":"10.1016/j.ejpb.2026.114989","DOIUrl":"10.1016/j.ejpb.2026.114989","url":null,"abstract":"<div><div>Nanoparticles are frequently designed as carriers to mediate the active transport of their cargo to the site of action, thereby serving as effector particles. However, after their in vivo administration, they become quickly recognized by immune cells and are cleared from the systemic circulation. This significantly impairs the nanoparticles’ targeting efficiency and shifts the target/off-target ratio toward metabolizing organs. As engineering-driven strategies, such as the PEGylation of their surface, require major modifications of the nanoparticles’ structure and do not appear to achieve the desired level of effectiveness, synergistic approaches are attracting increasing attention. They rely on the transient blockade of the immune system through endocytosis inhibitors or decoy nanomaterials. In the present study, we introduce a further development of these synergistic approaches by loading lipid nanocapsules (LNCs) as decoy nanoparticles with the endocytosis inhibitor chloroquine. Two principal advantages can be ascribed to this refined synergistic approach: First, encapsulation of the endocytosis inhibitor paves the way for pioneering subcutaneous application as a novel route of administration for the effector nanoparticles, as phagocytic cells within the lymphatic system can be selectively targeted. Second, the established co-administration regime constitutes a transferable concept across diverse settings without the need for structural modifications of the respective effector nanoparticles. Here, we report the successful in vitro establishment of this refined coadministration regime. Preincubation with chloroquine-loaded LNCs led to a statistically significant uptake inhibition of model effector nanoparticles into macrophages. Moreover, we investigated, for the first time, the incorporation of 1,2-Dioleoyl-<em>sn</em>-glycero-3-phosphoserine as a macrophage-specific targeting structure into the decoy LNCs’ envelope and its effect on the phagocytosis activity of macrophages.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"221 ","pages":"Article 114989"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009357","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":"The THP-1 cell line as a model for the assessment of monoclonal antibodies aggregates’ immunological effects","authors":"Maria Lteif ,&nbsp;Sara Abratanska ,&nbsp;Isabelle Turbica ,&nbsp;Marc Pallardy","doi":"10.1016/j.ejpb.2026.114990","DOIUrl":"10.1016/j.ejpb.2026.114990","url":null,"abstract":"<div><div>Immunogenicity is a major challenge to the development of biotherapeutics, and it is now well admitted that aggregation of therapeutic antibodies contributes to inducing an immunogenic response. The aim of this work was to investigate the THP-1 cell line as a model to evaluate antibodies (Ab) aggregates’ immunological effects, by studying internalization and cell activation. We generated aggregates by submitting infliximab (IFX), an immunogenic anti–TNF-α chimeric Ab, to a heat stress for various time of incubation. Of importance, some IFX aggregates, that were generated in mild conditions, altered THP-1 phenotype. Our results also showed that IFX aggregates are more internalized by THP-1 compared to the native antibody. Larger IFX aggregates, in particular, were able to modify THP-1 cells phenotype through the activation of the FcγRIIa-Syk pathway and to activate Syk in a Src-dependent manner. ERK kinase was also activated. Taken together, our results highlight the possibility of using the THP-1 cell line to assess the biological effects of Abs aggregates by measuring membrane markers and internalization.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"221 ","pages":"Article 114990"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002875","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":"Facile Formulation of an Oral Nanovesicular Carrier Co-Encapsulating Simvastatin and Ezetimibe for Enhanced Lipid-Lowering Effect","authors":"Abdelrahman A. Elfarouny,&nbsp;Yusuf A. Haggag,&nbsp;Ebtessam A. Essa,&nbsp;Sanaa A. El-Gizawy","doi":"10.1016/j.ejpb.2026.115003","DOIUrl":"10.1016/j.ejpb.2026.115003","url":null,"abstract":"<div><div>Simvastatin/Ezetimibe (SIM/EZE) is a widely prescribed hypolipidemic drug combination that provides substantial cardiovascular protection, particularly in high-risk patients. However, its poor dissolution and extensive first-pass metabolism limit gastrointestinal bioavailability, necessitating higher doses and thereby increasing the risk of adverse effects. In this study, we report a facile, robust, and easily scalable cholesterol–surfactant based nanocarrier system to enhance the oral delivery of SIM/EZE. Nanoparticles were prepared using Span 60 or Tween 80 in combination with cholesterol and optimized <em>via</em> a 2³ factorial experimental design. The effects of surfactant type, surfactant-to-cholesterol ratio, and sonication time on formulation characteristics were systematically investigated. The optimized formulation, prepared with 1200 mg Span 60, 300 mg cholesterol, 40 mg SIM, and 10 mg EZE and sonicated for 40 min, exhibited spherical morphology, a small particle size (109.6 nm), a zeta potential of (−37.91 mV), and high encapsulation efficiency (97.39 % for SIM and 88.79 % for EZE). Stability testing confirmed the absence of degradation under physiological conditions and showed no significant changes over three months of storage. In vivo evaluation in a hyperlipidemic rat model demonstrated that the optimized formulation significantly reduced total cholesterol levels compared with both the marketed product (Inegy™) and the drug suspension, indicating enhanced oral absorption. These findings highlight the potential of this nanoparticle system as an effective platform to improve the therapeutic efficacy of the SIM/EZE fixed-dose combination.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"221 ","pages":"Article 115003"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017865","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":"Preparation, Characterization, Pharmacokinetics, and Anti-Idiopathic pulmonary fibrosis activity of Bisdemethoxycurcumin liposomes","authors":"Ke Wang ,&nbsp;Qilong Wang ,&nbsp;Michael Adu-Frimpong ,&nbsp;Hui Ding","doi":"10.1016/j.ejpb.2026.115006","DOIUrl":"10.1016/j.ejpb.2026.115006","url":null,"abstract":"<div><div>Bisdemethoxycurcumin (BDMC) exhibits anti-inflammatory, antioxidant, and antitumor properties. Nonetheless, there is currently no published evidence regarding its efficacy in the management of idiopathic pulmonary fibrosis (IPF). Low solubility in water and reduced bioavailability of BDMC upon oral administration limit its application in the clinics. This study aimed to prepare D-α-tocopherol polyethylene glycol (PEG)-1000-succinate (TPGS)- and 1, 2-distearoyl-<em>sn</em>-glycero-3-phospho-ethanolamine (DSPE)-PEG-modified BDMC-loaded liposomes (BDMC-TPGS-DSPE-PEG-L) using the thin-film dispersion technique. Regarding formulation optimization, we employed single-factor experiments combined with Box–Behnken design (BBD). The physicochemical properties, in vitro release characteristics, and pharmacokinetic profiles of the prepared liposomes were systematically characterized. Furthermore, the anti-fibrotic activity of BDMC-TPGS-DSPE-PEG-L was evaluated in bleomycin (BLM)-induced A549 cells via MTT assay, senescence-associated β-galactosidase (SA-β-Gal) staining, and immunohistochemical analysis of Collagen-I. The optimal formulation showed favorable characteristics, namely particle size (PS), polydispersed index (PDI), zeta potential, encapsulation efficiency (EE%) and drug loading (DL) to be 232.36 ± 3.75 nm, 0.249 ± 0.016, −28.71 ± 0.976 mV, 95.98 ± 0.02%, and 6.84 ± 0.002%, respectively. The liposomal formulation significantly enhanced BDMC oral bioavailability by 1.6-fold compared to free BDMC. The results of the MTT assay confirmed that the cell inhibition rate of the liposome group decreased in a concentration-dependent manner, which was significantly lower compared to free drug group at the same concentration (P &lt; 0.05). Moreover, microscopic observation showed that high-concentration liposome group significantly reduced senescence-associated β-galactosidase (SA-β-Gal) activity and type I collagen (Collagen-I) expression compared to free BDMC. Altogether, BDMC-liposomes could effectively improve the solubility and bioavailability of BDMC, thereby providing a novel therapeutic option for IPF.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"221 ","pages":"Article 115006"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137317","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":"Computational analysis of the impact of urine volume on magnetic nanoparticle hyperthermia in the treatment of non-muscle-invasive bladder cancer","authors":"Sahar Marami ,&nbsp;Mohammad Hossein Tavakoli ,&nbsp;Abdolazim Sedighi Pashaki ,&nbsp;Safoora Nikzad","doi":"10.1016/j.ejpb.2026.114992","DOIUrl":"10.1016/j.ejpb.2026.114992","url":null,"abstract":"<div><div>Magnetic nanoparticle hyperthermia (MNP-HT) has emerged as a promising non-invasive technique for targeted cancer therapy. This study presents a comprehensive computational analysis of the influence of urine volume on the efficacy of MNP-HT for the treatment of T1 non-muscle-invasive bladder cancer (NMIBC). A two-dimensional axisymmetric finite element model was developed, coupling solid tissue heat transfer with intravesical fluid dynamics. Magnetite (Fe₃O₄) nanoparticles with a mean diameter of 19 nm were excited using an alternating magnetic field at a frequency of 100 kHz. Four clinically relevant urine volumes (60, 120, 240, and 400 mL) were simulated to evaluate their effects on magnetic field distribution, nanoparticle power dissipation, convective heat transfer, and temperature distributions in both tumor and surrounding healthy tissues. Tissue heating was modeled using the Pennes bioheat equation, while urine flow and thermal transport were governed by the Navier–Stokes and energy equations. The results demonstrate a clear inverse relationship between urine volume and hyperthermia efficiency. Average tumor temperatures decreased from 41.89 °C at 60 mL to 41.51 °C at 400 mL due to enhanced convective cooling and reduced magnetic field–dependent nanoparticle power dissipation, while healthy tissue temperatures remained within safe therapeutic limits. These findings highlight urine volume as a critical physiological parameter influencing MNP-HT performance. To optimize thermal efficacy, clinical protocols should aim to minimize bladder urine volume before and during treatment through bladder emptying strategies and careful monitoring of bladder refilling.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"221 ","pages":"Article 114992"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988973","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":"Re-purposed phenobarbital-loaded squarticles: A novel approach for the topical management of chemotherapy-induced alopecia“","authors":"Salma A. Fereig ,&nbsp;John Youshia ,&nbsp;Ghada M. El-Zaafarany ,&nbsp;Mona G. Arafa ,&nbsp;Mona M.A. Abdel-Mottaleb","doi":"10.1016/j.ejpb.2026.115005","DOIUrl":"10.1016/j.ejpb.2026.115005","url":null,"abstract":"<div><h3>Background</h3><div>Chemotherapy-induced alopecia (CIA) causes significant psychological distress, prompting the need for effective prophylactic or therapeutic interventions. Phenobarbital, a potential agent for re-purposing towards CIA prophylaxis and/or treatment, activates ABC receptors to expel chemotherapeutic agents from hair follicles. Squarticles, nanostructured lipid carriers enriched with squalene, are emerging nanocarriers that selectively target hair follicles via interaction with physiological sebum.</div></div><div><h3>Methods</h3><div>This study developed phenobarbital-loaded squarticles using a cost-effective high-speed stirring-ultrasonication method. Key formulation variables included total lipid amount (1% or 2%), precirol-to-squalene ratio (0:1, 3:1, 1:1, 1:0), and surfactant concentration (0.25% or 0.5%)</div></div><div><h3>Results</h3><div>The optimized formulation displayed a particle size of 229 ± 16.7 nm and drug entrapment efficiency of 82.72 ± 3.02%. Further characterization of the optimized formula demonstrated controlled drug release following the Higuchi pharmacokinetic model, with ∼ 11% of the drug deposited in hair follicles. Confocal laser scanning examination of skin specimens with DiI-loaded squarticles confirmed follicular targeting. In vivo studies on cyclophosphamide-induced alopecia in mice showed that both phenobarbital-loaded and blank squarticles provided a degree of hair follicle protection, accelerated recovery, and promoted cellular proliferation, as verified by histopathology, SEM imaging, and Ki-67 immunohistochemistry.</div></div><div><h3>Conclusions</h3><div>Both blank and drug-loaded squarticles demonstrated potential as prophylactic/therapeutic agents against CIA.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"221 ","pages":"Article 115005"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050974","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":"Trp2 cationic liposomes doped with manganese adjuvant potently activate dendritic cells to enhance antitumor activity against melanoma in mice","authors":"Chengke Ding,&nbsp;Huiting Li,&nbsp;Pengbo Han,&nbsp;Yan Zhao","doi":"10.1016/j.ejpb.2026.114991","DOIUrl":"10.1016/j.ejpb.2026.114991","url":null,"abstract":"<div><div>Tyrosinase-related protein 2 (Trp2) peptide-based vaccines hold great promise for melanoma immunotherapy, however, their application is often limited by inefficient antigen delivery, inadequate dendritic cell (DC)-mediated immune activation, and an immunosuppressive tumor microenvironment. To address these challenges, we developed an engineered cationic liposome vaccine platform for co-delivering Trp2 and a manganese-based adjuvant (MnJ). The Trp2-DOTAP-Lipo/MnJ system facilitates efficient antigen delivery to antigen-presenting cells via electrostatic interactions between the cationic lipid bilayer and negatively charged cell membranes, significantly enhancing antigen uptake, promoting DC maturation, stimulating the secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and levels of interleukin-6 (IL-6), and increasing cytotoxic T lymphocyte infiltration. Acting as a key amplifier of antigen-specific immunity, MnJ enhances antigen presentation and effector functions, which together with its role in localizing cytokine production, potently enhances anti-tumor immunity while minimizing systemic toxicity. In a murine melanoma model, Trp2-DOTAP-Lipo/MnJ exhibited significantly improved tumor suppression and extended survival. By combining nanocarrier engineering with innate immune activation, this strategy offers a robust combinatory therapeutic approach for melanoma, leveraging efficient antigen delivery and localized immunomodulation to overcome key obstacles in cancer immunotherapy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"221 ","pages":"Article 114991"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976675","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":"Sulfasalazine–quercetin co-amorphous systems: Sustained release behaviors and enhanced pharmacokinetics","authors":"Jia Deng ,&nbsp;Jiangying Li ,&nbsp;Yangwen Peng ,&nbsp;Qian Dai ,&nbsp;Ningbo Pang ,&nbsp;Zhe Wang ,&nbsp;Hailu Zhang ,&nbsp;Xin Chen","doi":"10.1016/j.ejpb.2025.114972","DOIUrl":"10.1016/j.ejpb.2025.114972","url":null,"abstract":"<div><div>Sulfasalazine (SULF) is a well-established therapeutic agent for rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), but its oral absorption is limited by efflux transporters, particularly MRP2 and BCRP. Consequently, high daily doses (1–3 g) and frequent administration (three to four times daily) are required, increasing the risk of adverse effects during long-term therapy. To overcome these limitations, co-amorphous systems (CASs) of SULF with quercetin (QUE) were developed in this study. The CASs were systematically characterized using powder X-ray diffraction (PXRD), polarized light microscopy (PLM), scanning electron microscopy (SEM), and temperature-modulated differential scanning calorimetry (mDSC). The molecular-level formation mechanism was further elucidated via Fourier-transform infrared spectroscopy (FTIR) and molecular dynamics (MD) simulations. All SULF–QUE CASs exhibited glass transition temperatures around 113 °C and demonstrated sustained-release behavior, with markedly lower SULF dissolution (24.5–42.9 %) compared to the crystalline form (89.8 %) after 6 h. This reduction was attributed to the in situ formation of a dense “shell-like” recrystallized QUE surface structure resulting from its incongruent dissolution. Importantly, co-amorphous forms demonstrated enhanced oral bioavailability (1.52–2.80-fold) and prolonged <em>T</em>_max (1.84–5.52-fold) compared to crystalline SULF, fulfilling the original goal of their development. Moreover, these systems exhibited satisfactory physical stability over time. Overall, the SULF–QUE CASs present a promising strategy to optimize the clinical dosage of SULF, reduce side effects, and offer a synergistic therapeutic approach for RA and IBD.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114972"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827148","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}