European Journal of Pharmaceutical Sciences最新文献

{"title":"Population pharmacokinetics of mycophenolic acid and Bayesian estimator in lung transplant adults recipients in the early post-transplant period","authors":"Juliette Kauv ,&nbsp;Séverine Feuillet ,&nbsp;Aurélie Barrail-Tran ,&nbsp;Alexandra Delemos ,&nbsp;Tiphaine Legrand ,&nbsp;Céline Verstuyft ,&nbsp;Jérome Le Pavec ,&nbsp;Emmanuelle Comets ,&nbsp;Valérie Furlan","doi":"10.1016/j.ejps.2025.107290","DOIUrl":"10.1016/j.ejps.2025.107290","url":null,"abstract":"<div><div>Mycophenolic acid (MPA), administered as its prodrug Mycophenolate mofetil (MMF), is widely used to prevent rejection after organ solid transplantation. Few population pharmacokinetic studies of MPA in lung transplantation are available, so the present study was designed to describe the population pharmacokinetics (PK) of MPA and develop a maximum a posteriori Bayesian estimator of MPA area under the curve (AUC0-12h) in lung transplant (LT) recipients in the early post-transplant period.</div><div>We conducted a single-center retrospective study in the Plessis-Robinson hospital (France), including LT recipients receiving MMF in whom at least one concentration-time profile was available during the first 3 months post-transplantation. MPA was measured before intake and 0.5, 1, 2, 4 ± 6 hours post-administration. Patients were divided into an index group (N=72) and a validation group (N=46). A population PK model and a Bayesian estimator with three sampling times were built with the index dataset and externally evaluated with the validation dataset. Analyses were performed using nonlinear mixed-effects models with Monolix® software.</div><div>The PK model was built using 97 MPA profiles in the index dataset. MPA PK was best described using a two-compartment model with a lag time and first-order absorption and elimination. The significant covariates on the MPA apparent clearance were creatinine, body weight and ciclosporin co-administration and the posttransplantation time on the apparent volume of the central compartment. The model was successfully evaluated in the 60 MPA profiles from the validation dataset. The best Bayesian estimator included samples just before intake, 1 and 4 hours post-administration. The prediction of AUC was unbiased in both datasets and had a precision around 20 %. This is the first Bayesian estimator allowing the prediction of AUC in LT patients without cystic fibrosis in the early post-transplant period, providing a tool to improve the therapeutic drug monitoring of MPA.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107290"},"PeriodicalIF":4.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transport protein interaction and target pathway analysis of a hybrid antifungal compound synthesized by linking triazolothiadiazine ring system with the pyridine ring","authors":"Tanveer A. Wani ,&nbsp;Mohammed S. Alsalhi ,&nbsp;Ahmed H. Bakheit ,&nbsp;Abdulrahman A. Al-Majed ,&nbsp;Mashooq A. Bhat ,&nbsp;Halah S. Almutairi ,&nbsp;Humidah Alanazi ,&nbsp;Seema Zargar","doi":"10.1016/j.ejps.2025.107289","DOIUrl":"10.1016/j.ejps.2025.107289","url":null,"abstract":"<div><div>The present manuscript explores the serum albumin interaction and target pathway analysis of a newly developed antifungal agent, 7-[2-(4-chlorophenyl) hydrazinylidene]-6-methyl-3-(pyridin-4-yl)-7H-[1, 2, 4]triazolo[3,4-b][1, 3, 4]thiadiazine (5E). Candida species are among the leading causes of systemic fungal infections, highlighting a need for new effective antifungal therapies because of drug resistance and associated side effects with existing treatment regimens. The synthesized compound (5E) demonstrated superior antifungal characteristics in comparison to ketaconazole, suggesting potential for more effective therapeutic options. Serum albumins in plasma binds and carries molecules, including drugs. Spectroscopic techniques, computational methods and target pathway analysis were employed for studying BSA-5E interactions. The compound 5E quenched BSA fluorescence via static quenching. The 5E primarily interacts with the IIA and IIIA subdomains of BSA which was aided by hydrogen binding. The target prediction tool of SwissADME predicted kinases, particularly CDK5R1, CDK5, PLK1, FLT1, KDR, and NTRK1, to be the most significant targets of 5E, followed by enzymes including lyases and oxidoreductases. GeneMANIA analysis identified key kinase-regulating lyases and oxidoreductase for carrying out antifungal action. The associated miRNAs were depicted by MIENTURNET providing insights into its pharmacokinetics and therapeutic potential at molecular level. Molecular docking aided to comprehend the BSA-5E interaction at protein level.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107289"},"PeriodicalIF":4.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Michaelis-Menten: A modified enzyme kinetics equation improves drug metabolism prediction in bottom-Up PBPK modeling","authors":"Junghyun Lee ,&nbsp;Yun Min Song ,&nbsp;Hwi-yeol Yun ,&nbsp;Suein Choi ,&nbsp;Jae Kyoung Kim","doi":"10.1016/j.ejps.2025.107286","DOIUrl":"10.1016/j.ejps.2025.107286","url":null,"abstract":"<div><div>Physiologically based pharmacokinetic (PBPK) models are widely used methodology that dynamically integrates diverse biological parameters to predict pharmacokinetic profiles of drugs and their metabolites. Traditionally, PBPK models rely on the Michaelis-Menten (MM) equation to describe enzymatic rate processes such as transport, metabolism, and secretion in terms of intrinsic clearance. However, the MM equation assumes that enzyme concentrations (<span><math><msub><mi>E</mi><mi>T</mi></msub></math></span>) are substantially lower than the MM constant (<span><math><msub><mi>K</mi><mi>M</mi></msub></math></span>). This condition is often violated in vivo, resulting in inaccuracies in predicting clearance and drug-drug interactions. To address these inaccuracies, current PBPK approaches employ parameter optimization using phase I clinical trial data. However, this conflicts with the bottom-up paradigm of predicting human pharmacokinetics from preclinical data prior to human trials. Here, we resolve this conflict by implementing a modified metabolic rate equation within the PBPK modeling framework. Unlike the MM equation, the modified equation remains valid even when <span><math><msub><mi>E</mi><mi>T</mi></msub></math></span> is comparable to <span><math><msub><mi>K</mi><mi>M</mi></msub></math></span>, thereby improving prediction accuracy in static models. Our results demonstrate that using the modified equation outperforms the conventional MM-based method even in dynamic PBPK modeling, particularly in scenarios where the MM equation's assumptions are invalid. Based on these findings, we propose expanded guidelines to broaden the applicability of PBPK modeling using the modified equation. This advancement offers a significant contribution to pharmacokinetic research and enhances the utility of PBPK models in drug development.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107286"},"PeriodicalIF":4.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and in vitro evaluation of polyethylene glycol-treprostinil conjugates for sustained local delivery in pulmonary arterial hypertension","authors":"Giuditta Leone ,&nbsp;Bernard Ucakar ,&nbsp;Frédéric Perros ,&nbsp;Raphaël Frédérick ,&nbsp;Rita Vanbever","doi":"10.1016/j.ejps.2025.107287","DOIUrl":"10.1016/j.ejps.2025.107287","url":null,"abstract":"<div><div>Treprostinil (TRE) is a prostacyclin analogue approved for the treatment of pulmonary arterial hypertension (PAH). Despite its effectiveness, TRE has a short half-life, necessitating frequent or continuous administration to maintain therapeutic levels while minimizing adverse effects. To improve pharmacokinetics and pulmonary targeting of TRE, we designed a series of polyethylene glycol (PEG) ester conjugates for inhalation. The increase in molecular size achieved through polymer conjugation prevents the passive diffusion of TRE across the alveolar-capillary barrier, a common drawback of small, lipophilic drugs delivered to the lungs. The ester bond between TRE and PEG enables a gradual release of the active compound within the alveolar space. TRE was chemically modified with seven different alkyne-bearing linkers and subsequently conjugated to PEG-azide 6 kDa via click chemistry. These linkers were strategically designed to modulate the chemical environment around the cleavable ester bond, allowing for the systematic evaluation of the steric and electronic effects on the stability of the PEG-TRE conjugates. Drug release studies in bronchoalveolar lavage from healthy rats demonstrated that sterically hindered and electronically stabilized linkers significantly slowed the release of TRE. Moreover, conjugate stability was dependent on the enzymes availability, with a higher conjugate-enzyme ratio leading to slower release, suggesting enzyme saturation as a potential mechanism for controlled drug release. Overall, these findings demonstrate a tunable strategy for releasing drugs from polymer-drug conjugates in biological media.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107287"},"PeriodicalIF":4.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional hydrogel for the treatment of atopic dermatitis: current advances and translational challenges","authors":"Li Wan ,&nbsp;Miaohui Wang ,&nbsp;Yuqian Song ,&nbsp;Genong Sun ,&nbsp;Ruihan Zhang ,&nbsp;Zhuoya Chen ,&nbsp;Yibing Zhou ,&nbsp;Keqiang Ma ,&nbsp;Rui Zheng ,&nbsp;Martin Gluchman ,&nbsp;Jing Li ,&nbsp;Chenyu Zhao","doi":"10.1016/j.ejps.2025.107288","DOIUrl":"10.1016/j.ejps.2025.107288","url":null,"abstract":"<div><div>Atopic dermatitis (AD), the most common chronic inflammatory skin disease, is characterized by intense pruritus and varying degrees of cutaneous inflammation. Current therapeutic modalities (such as topical corticosteroids and biologics) can control symptoms in the short term, but limitations including extremely low bioavailability and significant side effects substantially restrict their clinical efficacy in AD management. Therefore, more precise and safer local management strategies for AD represent the most promising direction for future development. As a biomaterial with a three-dimensional network structure combining biomimetic properties and sustained drug delivery capability, hydrogel emerges as an optimal carrier choice. Multiple clinical trials have demonstrated that Desonide hydrogel provides substantial benefits to patients, making the design of multifunctional hydrogel dressings a research hotspot in recent years. This review first summarizes the feasible options for drug loading in hydrogels, then focuses on the advantages and disadvantages of different hydrogel types and drug delivery methods, and finally addresses the challenges and solutions for translating innovative hydrogels into clinical practice. Aimed at integrating perspectives from materials science, dermatology, and translational medicine, this review establishes a theoretical framework for the rational design of innovative hydrogels in local AD therapy.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107288"},"PeriodicalIF":4.7,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing amorphous multidrug formulations: A particle engineering approach through spray drying","authors":"Mira El Sayed ,&nbsp;Amjad Alhalaweh ,&nbsp;Arash Asdagh ,&nbsp;Lucia Kovac ,&nbsp;Christel A.S. Bergström","doi":"10.1016/j.ejps.2025.107285","DOIUrl":"10.1016/j.ejps.2025.107285","url":null,"abstract":"<div><div>Despite advances in the field of multidrug formulations, developing and manufacturing them still poses substantial challenges, particularly for drugs with low aqueous solubility. Here, this critical issue was addressed by engineering amorphous multidrug formulations with optimized performance at the site of absorption using the spray drying technique. Formulations containing atazanavir and ritonavir, alone or in combination, were produced by spray drying. Excipient content in aqueous solution was optimized to generate a stable feed suspension of amorphous particles with controlled particle size. The powder formulations were characterized by powder X-ray diffraction (PXRD), thermal analysis, laser diffraction, and scanning electron microscopy (SEM). The drug content was assayed, and a dissolution study was performed. Dynamic light scattering was used to measure particle size of the colloidal phase in the feed suspension and after dissolution of powder. A stability study was conducted at 25 °C/60 % RH and 40 °C/75 % RH condition for 4 weeks. DSC and PXRD confirmed the formulations to be amorphous. Drug content in the spray-dried formulations ranged from 98 to 108 %. Laser diffraction measured the particles to be from 5–10 µm and SEM showed they had wrinkled and irregularly shaped surfaces. The particle size of the colloidal phase formed upon dissolution of combination formulation was stable at 900 nm over 120 min. The formulations remained amorphous under both studied conditions throughout the stability study period. These findings highlight the potential of particle engineering, where a mechanistically informed selection of excipients is combined with an appropriate spray-drying process, to achieve highly stable and robust amorphous multidrug formulations —critical for ensuring effective drug performance and patient treatment.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107285"},"PeriodicalIF":4.7,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective formation of coamorphous systems with enzalutamide: Benzene rings as key structural features","authors":"Argyro Chatziadi,&nbsp;Kateřina Neubergerová,&nbsp;Venkata Krishna Rao Balaga,&nbsp;Dan Trunov,&nbsp;Miroslav Šoóš","doi":"10.1016/j.ejps.2025.107281","DOIUrl":"10.1016/j.ejps.2025.107281","url":null,"abstract":"<div><div>Enzalutamide (ENZ), a non-steroidal antiandrogen used in the treatment of metastatic castration-resistant prostate cancer, exhibits poor aqueous solubility and bioavailability. Coamorphous systems, formed between an active pharmaceutical ingredient (API) and a low-molecular-weight coformer, offer a promising strategy to enhance solubility and dissolution. Here, we systematically screened a range of small organic acids and amino acids as coformers for coamorphous system formation with ENZ. Interestingly, full coamorphous systems formed exclusively with coformers containing a benzene ring, including benzoic acid, salicylic acid, 2-aminobenzoic acid, 2,5-dihydroxybenzoic acid (25H), L-phenylalanine, and L-tryptophan. Crystal structure analysis revealed that ENZ is stabilized in its crystalline state through strong π–π stacking, but these interactions are weakened or disrupted upon amorphization. Coamorphization is facilitated by coformers that can stabilize the amorphous phase through molecular complementarity and favorable packing. FTIR indicated limited new strong interactions, suggesting stabilization mainly via molecular mixing and weak π–π contacts. Thermal analysis confirmed single-phase systems with distinct T_g values, and stability studies revealed that the ENZ–25H system remained amorphous for nearly four months, outperforming others. Dissolution testing demonstrated up to a 3.6-fold increase in intrinsic dissolution rate compared with crystalline ENZ. These results identify aromaticity as a critical structural feature for coamorphous formation with ENZ and provide a rational basis for coformer selection for this drug and, by extension, other aromatic-rich, poorly soluble APIs.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107281"},"PeriodicalIF":4.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approaching drug release performance from mesoporous silica formulations by modeling of chemical potentials","authors":"Andreas Niederquell ,&nbsp;Annika Hofer ,&nbsp;Barbora Vraníková ,&nbsp;Martin Kuentz","doi":"10.1016/j.ejps.2025.107283","DOIUrl":"10.1016/j.ejps.2025.107283","url":null,"abstract":"<div><div>Mesoporous silica are promising bio-enabling carriers for poorly soluble drugs. However, a comprehensive understanding of drug-silica interactions and their impact on drug release remains limited. Apart from urgently needed experimental tools, predictive <em>in silico</em> tools that consider drug-carrier interactions in aqueous media are currently lacking. To address this gap, a novel <em>in silico</em> approach (silica-water partitioning coefficient) was introduced in this study. A series of ten drugs were loaded onto a mesoporous carrier (Parteck® SLC 500), and the products were analyzed using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). In vitro dissolution (USP II) profiles of drug-loaded formulations were analyzed and correlated with a newly introduced silica-water partitioning coefficient derived from chemical potential calculations using the Conductor-like Screening Model for Real Solvents (COSMO-RS). Strong correlations were observed between dissolution parameters, such as the initial release slopes (Pearson r = -0.98; <em>p</em> = &lt; 0.05) and AUC values (Pearson <em>r</em> = -0.79; <em>p</em> &lt; 0.05), and the calculated chemical potential-based partitioning coefficient. This study introduces a predictive method based on COSMO-RS-derived chemical potentials to estimate silica-water partitioning for drugs, thereby predicting their release performance from mesoporous silica formulations. The results demonstrate that these calculated chemical potentials can qualitatively rank the drug release kinetics in aqueous media. Further investigation with additional compounds and carrier types may broaden the applicability of this approach as a mechanistic tool for mesoporous silica formulation development and contribute to narrowing the gap toward future clinical translation.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107283"},"PeriodicalIF":4.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D printed mucoadhesive films: Individualized drug dosing for localized drug delivery","authors":"Friederike Brokmann,&nbsp;Sophia Grzam,&nbsp;Jonas Fynn Kandzi,&nbsp;Julius Krause","doi":"10.1016/j.ejps.2025.107284","DOIUrl":"10.1016/j.ejps.2025.107284","url":null,"abstract":"<div><div>Mucoadhesive films enable non-invasive and localized drug delivery. Among various manufacturing methods, this study focuses on fused deposition modeling (FDM) using an advanced two-nozzle 3D printing system. This technique allows the fabrication of two-part films containing spatially separated verum (drug) and placebo segments, enabling flexible and individualized drug dosing within a single dosage form. Caffeine was used as a model drug to produce and compare 3D printed films with those made by solvent casting (SC). Mechanical, optical, and dissolution properties were assessed. While SC films showed higher extensibility and lower tensile strength, 3D printed films—especially the two-part designs—exhibited greater tensile strength but reduced flexibility. Both SC and 3D printed films showed similar mucoadhesive properties, indicating that the manufacturing method does not significantly influence adhesion to mucosal surfaces. Two-nozzle printing approach proved effective in precisely combining verum and placebo regions, offering potential for site-specific drug delivery, such as treatments targeting the esophagus. Additionally, drug loading can be adjusted by varying the ratio between placebo and verum filaments. This work highlights the versatility of multi-material 3D printing for producing mucoadhesive films and paves the way for personalized therapies across different indications.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107284"},"PeriodicalIF":4.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the blood-brain barrier with lipoprotein-mimicking nanoparticles loaded with flurbiprofenaxetil and coated with apolipoprotein E3","authors":"M. Laabs,&nbsp;D. Mulac,&nbsp;K. Langer","doi":"10.1016/j.ejps.2025.107272","DOIUrl":"10.1016/j.ejps.2025.107272","url":null,"abstract":"<div><div>In previous studies, it has been demonstrated that lipoprotein-mimicking nanoparticles with a solid lipid core of cholesteryl oleate, a lecithin coating and adsorptively bound apolipoprotein E₃ (ApoE) may serve as a potential vehicle for drug delivery to the central nervous system. In this study, the impact of drug characteristics, particularly lipophilicity, was evaluated to achieve a stable incorporation of model drugs into these lipid-based nanoparticles (LNPs). This study explored the lipophilicity of flurbiprofen, a potential drug in the treatment of Alzheimer’s disease (AD), and its prodrug flurbiprofenaxetil across varying pH levels. Our findings highlight how flurbiprofen’s lipophilicity was influenced by its protonation state, affecting its incorporation into LNPs and consequently its release behaviour under physiological conditions, while flurbiprofenaxetil showed minimal variations due to its chemical structure. We also investigated the interaction between lipoprotein mimicking nanoparticles and primary porcine brain capillary endothelial cells to improve drug delivery across the blood-brain barrier (BBB). Permeation studies indicated that modification with ApoE enhanced the bidirectional permeability of LNPs across the BBB through receptor-mediated transcytosis. Furthermore, we demonstrated and identified the uptake mechanism involving the low density lipoprotein receptor-related protein 1 (LRP1), allowing these LNPs to be recognized by the same receptors as endogenous lipoproteins. Overall, these findings highlight the potential of ApoE modified LNPs as a promising strategy for targeted drug delivery to the brain.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107272"},"PeriodicalIF":4.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}