European Journal of Pharmaceutical Sciences最新文献

{"title":"Simulating extractables and leachables in biopharmaceutical manufacturing to support safety assessment","authors":"Maximilian Bossong ,&nbsp;Armin Hauk ,&nbsp;Ina Pahl ,&nbsp;Roberto Menzel ,&nbsp;Peter Langguth","doi":"10.1016/j.ejps.2025.107262","DOIUrl":"10.1016/j.ejps.2025.107262","url":null,"abstract":"<div><div>The use of single-use systems in the manufacturing of biopharmaceuticals raises concerns about the accumulation of process equipment-related leachables in their production and purification processes. However, this risk is mitigated by effective sinks in the manufacturing processes and dilution of product flow, for example, in tangential-flow-filtration. This paper presents a modeling approach that combines the release and adsorption of compounds with dynamic process conditions of biopharmaceutical processes. These calculations help assess process criticality by identifying sources but also low-risk processes and components regarding extractables and leachables accumulation. This approach can significantly reduce the necessity for resource-intensive practical testing, such as leachable studies, which may be impractical from an analytical perspective due to the complex matrices in biopharmaceutical process streams.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107262"},"PeriodicalIF":4.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032923","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":"Platinum-group metal half-sandwich complexes with C-glucopyranosyl 1,2,3-triazoles and isoxazoles as ligands: synthesis and evaluation as antineoplastic and antimicrobial agents","authors":"Rahaf Akel ,&nbsp;Alshimaa I. Zaki ,&nbsp;Éva Kerekes ,&nbsp;István Kacsir ,&nbsp;György Attila Kiss ,&nbsp;Csongor Freytag ,&nbsp;Evelin Szoták ,&nbsp;Dóra Boros-Pál ,&nbsp;Eszter Anna Janka ,&nbsp;Gábor Kardos ,&nbsp;Peter Bai ,&nbsp;László Somsák ,&nbsp;Sándor Kun ,&nbsp;Adrienn Sipos ,&nbsp;Éva Bokor","doi":"10.1016/j.ejps.2025.107259","DOIUrl":"10.1016/j.ejps.2025.107259","url":null,"abstract":"<div><div>Half-sandwich complexes of platinum-group metals are a widely studied subgroup of organometallic compounds with promising anticancer and antimicrobial properties. Recently, we have published a set of polyhapto arene/arenyl Ru(II), Os(II), Ir(III) and Rh(III) complexes with hetaryl-substituted 1-<em>N</em>-glucopyranosyl-1,2,3-triazole and <em>C</em>-glycopyranosyl-1,3,4- and -1,2,4-oxadiazole-type N,N-bidentate ligands, several of which exhibited (sub)micromolar antineoplastic and bacteriostatic potencies. The structure-activity relationships of these series indicated that the nature of the azole ring and its way of connection to the pyranoid sugar unit played crucial roles in the biological activity of such complexes. In order to further study the influence of the five-membered heteroaromatic moiety, in this work we have synthesised new complexes with <em>O</em>-protected 4-<em>C</em>-(β-<span>d</span>-glucopyranosyl)-1-(pyridin-2-yl)-1,2,3-triazoles and 5-<em>C</em>-(β-<span>d</span>-glucopyranosyl)-3-(pyridin-2-yl)-isoxazoles as N,N-chelating ligands of η⁶-<em>p</em>-cym-Ru(II)/Os(II) and η⁵-Cp*-Ir(III)/Rh(III) complexes and have studied their cytostatic and antibacterial properties. All but the Rh(III)-derived complexes exerted cytostasis on a plethora of neoplasia cell models. The Ru(II)- and Os(II)-based complexes had the best IC₅₀ values. The isoxazole-containing compounds outperformed the triazole-containing ones in terms of their cytostatic properties with submicromolar IC₅₀ values. A subset of the complexes with Ru(II) and Ir(III) ions had bacteriostatic properties with low micromolar MIC values.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"215 ","pages":"Article 107259"},"PeriodicalIF":4.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023019","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":"Single-step, chloroform-free extraction of lysophosphatidylcholine from plasma for cancer biomarker analysis","authors":"Rebecca Vieth ,&nbsp;Marilena Wittmaack ,&nbsp;Birthe Gericke ,&nbsp;Gert Fricker ,&nbsp;Ulrich Massing","doi":"10.1016/j.ejps.2025.107258","DOIUrl":"10.1016/j.ejps.2025.107258","url":null,"abstract":"<div><div>Lysophosphatidylcholine (LPC) has been the subject of research for many years, but its role in lipid turnover is still not fully understood, neither its role in cancer development and progression. A crucial aspect in LPC research is its efficient and fast extraction from plasma and tissues to use LPC as a biomarker in clinical settings. The extraction methods commonly in use like Bligh &amp; Dyer require the use of toxic halogenated solvents and are time consuming due to multiple extraction steps and subsequent solvent evaporation. In this study, a new, salt-assisted one-step extraction protocol, which avoids halogenated solvents, is presented. Saturated ammonium acetate solution was used as a salt component and acetonitrile:isopropanol (2.5:1 v/v) as eluent. The new extraction is characterized by its simplicity, robustness and short total process time of 18 minutes. For validation according to the ICH M10 guideline for bioanalytical method validation, LPC species extracted from plasma were quantified by LC-MS/MS, using LPC 19:0 as internal standard. In addition to these advantages, the new extraction procedure showed a slightly but statistically significant better recovery compared to Bligh &amp; Dyer (93.2 % vs. 87.5 %; <em>p</em> &lt; 0.05; <em>n</em> = 5), as shown by a <em>t</em>-test. The applicability of the new method was demonstrated in a pilot study, in which the plasma of 15 healthy volunteers was analyzed for its content of various LPC species.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107258"},"PeriodicalIF":4.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008113","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":"Comparing Round Window Membrane Permeability Enhancers: An Animal Study.","authors":"Jae Sang Han, Ye Lin Kim, Kyusun Park, Ji Hyung Lim, Hong-Lim Kim, So Young Park, Shi Nae Park","doi":"10.1016/j.ejps.2025.107256","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107256","url":null,"abstract":"<p><p>Intratympanic (IT) delivery of dexamethasone (DEX) is widely used for treating inner ear disorders; however, its therapeutic efficacy is limited by poor permeability of the round window membrane (RWM). This study aimed to evaluate and compare the efficacy and safety of three pharmacological agents-histamine (HIS), 3% hypertonic saline (3% HS), and sodium caprate (SC)-as adjuvants for enhancing RWM permeability and improving IT-DEX delivery in a murine model. Following IT administration of each permeability enhancer followed by DEX injection, perilymph DEX concentrations were measured using ultra-high-performance liquid chromatography, and DEX receptor expression in the organ of Corti was assessed by immunofluorescence. Structural changes in the RWM were examined by transmission electron microscopy, and auditory function was evaluated using auditory brainstem response (ABR) testing. All three enhancers significantly increased perilymph DEX concentrations compared to controls, with 3% HS demonstrating the highest levels. 3% HS also induced the greatest DEX receptor expression and caused only transient RWM structural alterations without permanent damage. Despite enhanced drug delivery, no statistically significant differences in ABR threshold recovery were observed among treatment groups. These findings demonstrate that 3% HS is the most effective adjuvant among those tested for IT drug delivery, although enhanced inner ear drug penetration does not necessarily translate to improved functional recovery in this model.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107256"},"PeriodicalIF":4.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014141","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":"Platinum-group metal half-sandwich complexes of sugar-isoxazol(in)e conjugates - synthesis and evaluation of their antineoplastic and antimicrobial activities.","authors":"Rahaf Akel, István Kacsir, Éva Kerekes, Csongor Freytag, Evelin Szoták, Dóra Boros-Pál, Eszter Anna Janka, Attila Bényei, Gábor Kardos, Éva Bokor, László Somsák, Péter Bai, Adrienn Sipos, Sándor Kun","doi":"10.1016/j.ejps.2025.107260","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107260","url":null,"abstract":"<p><p>Platinum-group metal half-sandwich complexes are considered to be potential replacements of the clinically widely used platins which have several side effects and tend to cause resistance to develop. In our previous works, we used a range of 2-pyridyl-substituted N- and C-glycosyl heterocycles as N,N-chelating ligands to prepare ruthenium(II), osmium(II), iridium(III) and rhodium(III) polyhapto arene/arenyl half-sandwich complexes. Some of these complexes, particularly with the C-glucopyranosyl isoxazole derived ligand in its O-perbenzoylated form, exhibited greater anticancer efficiency than cisplatin and had minimal or negligible effects on non-transformed fibroblasts. Additionally, these cytostatic compounds exhibited micromolar antibacterial activity against multiresistant Gram-positive bacteria. In the present work, novel modes of conjugation between the sugar and the isoxazole moieties have been studied. Specifically, glycosylidene-spiro-isoxazoline and polyhydroxyalkylisoxazole scaffolds were synthesised and utilised in complex formation reactions. The spiro-isoxazolines were obtained in 1,3-dipolar cycloadditions of exo-glycals and nitrile oxides generated from pyridine-2-carbaldoximes. Ring opening of the spiro-isoxazolines under basic or transition-metal-mediated conditions produced polyhydroxyalkylisoxazoles. These compounds were then transformed into their O-peracetylated, O-perbenzoylated and O-unprotected variants, which were used for complex formation with the above-mentioned platinum-group metal ions. The complexes induced cytostasis in cellular models of ovarian cancer and pancreatic adenocarcinoma; the best compounds had submicromolar IC₅₀ values (0.4-0.5 µM). A subset of the cytostatic complexes retained their activity on cisplatin resistant ovarian cancer cells. Furthermore, a reasonable therapeutic index was detected when complexes were assessed on primary human fibroblasts pointing towards a potential applicability of the complexes. Unexpectedly, none of the complexes induced bacteriostasis in Gram-positive bacteria as Staphylococcus aureus or Enterococcus species.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107260"},"PeriodicalIF":4.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014213","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":"Diffusion of macromolecules in extracellular matrix mimetic hydrogels – effect of size and charge","authors":"Julia Parlow ,&nbsp;Eva Pet ,&nbsp;Anna Smirnova ,&nbsp;Enamul Mojumdar ,&nbsp;Helen Sjögren ,&nbsp;Per Hansson","doi":"10.1016/j.ejps.2025.107257","DOIUrl":"10.1016/j.ejps.2025.107257","url":null,"abstract":"<div><div>Subcutaneous (SC) injection is the primary alternative to oral administration for therapeutic proteins and peptides. However, bioavailability and absorption rate are often variable and difficult to predict. Therefore, there is a need for new biorelevant and predictive SC in vitro methods. In this study we systematically investigate the effect of size and charge of a macromolecule on its partitioning and diffusion within extracellular matrix (ECM) mimetic hydrogels in order to gain insight on interactions with the components of the ECM affecting the absorption of a drug after SC injection. Hydrogels consisting of either agarose, cross-linked collagen and hyaluronic acid (HA) or cross-linked HA, were made and equilibrated in solutions of FITC-dextrans of varying sizes (4 to 150 kDa) and model peptides of varying net charge (+2 to +9). Partitioning and diffusion coefficients within gel and solution were determined using confocal laser scanning microscopy and fluorescence recovery after photo bleaching (FRAP), and compared to theoretical models. Generally, the partitioning and diffusivities within the gels decreased with increasing molecular weight, which was in good agreement with models describing the effect of obstruction of the gel network corrected for heterogeneity in the gel structure. The cationic peptides were enriched in the oppositely charged gels and their diffusivities decreased with increasing peptide charge. The experimental results were in semi quantitative agreement with an electrostatic model presented in this work.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107257"},"PeriodicalIF":4.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008126","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":"Dual-action nanotherapy: Temozolomide-loaded, anti-PD-L1 scFv-functionalized lipid nanocarriers for targeted glioblastoma therapy","authors":"Eren Aytekin ,&nbsp;Semer Maksoud ,&nbsp;Bakhos A. Tannous ,&nbsp;Sibel Bozdağ Pehlivan ,&nbsp;Christian E. Badr","doi":"10.1016/j.ejps.2025.107255","DOIUrl":"10.1016/j.ejps.2025.107255","url":null,"abstract":"<div><div>Glioblastoma (GBM) is a highly malignant brain tumor with limited treatment options and poor prognosis.</div><div>GBM exhibits resistance to conventional therapies, including temozolomide (TMZ), radiotherapy, and immunotherapy, partly due to immunosuppressive mechanisms such as programmed death-ligand 1 (PD-L1) overexpression. To address these challenges, we developed TMZ-loaded nanostructured lipid carriers (NLCs) conjugated with anti-PD-L1 single-chain variable fragments (scFv) for dual chemo-immunotherapy.</div><div>The anti-PD-L1 scFv enabled active targeting of PD-L1-expressing tumor cells while mitigating immune evasion, and the NLCs efficiently crossed the blood-brain barrier (BBB), delivering TMZ to the tumor site. In vitro studies confirmed nanoparticle internalization by GL261 glioma cells and specific binding of the conjugated scFv to PD-L1. In vivo studies using the GL261/C57BL/6 mouse model demonstrated that TMZ-NLCs conjugated with anti-PD-L1 scFv (TMZ-NP-scFv) stabilized tumor growth by the third week, unlike other treatment groups. While all therapeutic groups (TMZ solution, TMZ-NP, and anti-PD-L1 scFv alone) significantly improved survival compared to controls, the TMZ-NP-scFv group exhibited the most pronounced survival benefit.</div><div>These results highlight the potential of TMZ-loaded, PD-L1-targeted NLCs as a synergistic strategy to enhance GBM treatment by combining chemotherapy and immune checkpoint blockade.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"213 ","pages":"Article 107255"},"PeriodicalIF":4.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008192","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":"Impact of the mucin barrier on the in vitro membrane permeability of cyclic peptides","authors":"Yuji Sakurai,&nbsp;Kazuhisa Ozeki,&nbsp;Haruka Tsutsui,&nbsp;Terushige Muraoka,&nbsp;Kimio Terao","doi":"10.1016/j.ejps.2025.107254","DOIUrl":"10.1016/j.ejps.2025.107254","url":null,"abstract":"<div><div>This study investigated the role of the mucin layer in cyclic peptide permeability using an <em>in vitro</em> assay system. We evaluated the membrane permeability of 18 cyclic peptides and reference compounds using biosimilar mucin and Caco-2/HT29 cells. The permeability of paracellular markers (FD4 and LY) and digoxin (a low molecular weight compound) remained unaffected by mucin presence when using biosimilar mucin. Conversely, cyclosporin A, a commercially available cyclic peptide drug, showed reduced permeability. In Caco-2/HT29 co-cultured cells compared with Caco-2 cells only, most compounds exhibited increased permeability due to enhanced interstitial permeability, except for cyclosporin A, which showed decreased permeability in the presence of mucin. Similarly, the permeability of LUNA18, a cyclic peptide under development, was reduced by 54.1 and 26.0 % in both Caco-2/HT29 co-cultured and HT29 cells. Furthermore, 12 of 18 cyclic peptides exhibited ≥ 2-fold decrease in membrane permeability in Caco-2/HT29 co-cultured cells. These findings suggest that current permeability evaluation methods, which do not account for the mucin layer, may overestimate the permeability of highly lipophilic cyclic peptides. The mucin layer may serve as a rate-limiting factor in cyclic peptide membrane permeability, highlighting the importance of including mucin layer permeability in cyclic peptide evaluation protocols.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107254"},"PeriodicalIF":4.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000081","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":"In vitro/in vivo evaluation of 3D bioprinted silk fibroin hydrogels for IBD: A dual mesalazine and TNF-α siRNA approach","authors":"Ayşegül Yıldız ,&nbsp;N.Başaran Mutlu-Ağardan ,&nbsp;Özge Özgenç Çınar ,&nbsp;Ahmet Ceylan ,&nbsp;Recep Uyar ,&nbsp;Begüm Yurdakök Dikmen ,&nbsp;Füsun Acartürk","doi":"10.1016/j.ejps.2025.107252","DOIUrl":"10.1016/j.ejps.2025.107252","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is a chronic, relapsing disease that poses significant challenges in treatment. This study aimed to develop silk fibroin-based mesalazine and chitosan:TNF-α siRNA polyplex-loaded, 3D bioprinted hydrogels for the oral treatment of IBD. For this purpose, bioink formulations composed of silk fibroin, hyaluronic acid, and sodium alginate were optimized. A chitosan:TNF-α siRNA polyplex was also formulated at a 40:1 chitosan-to-siRNA ratio. Hydrogel formulations were fabricated using 3D bioprinting and characterized in terms of compatibility, thermal stability, swelling behavior, degradation, mechanical properties, and mucoadhesion to both healthy and IBD-induced colon tissues. The optimized oral hydrogel (H-M-P12) demonstrated a swelling index of 366±67 % and underwent 31.2 % degradation after 24 h in vitro. Mesalazine and TNF-α siRNA exhibited a sustained release profile from the hydrogels. Cytotoxicity studies confirmed the biocompatibility of the hydrogels and a TNF-α gene silencing efficiency of 46.53 % was obtained. In vivo studies in a Balb/c mouse model of IBD revealed significant improvements in physiological parameters, macroscopic and microscopic morphology, and biochemical markers following treatment with the developed hydrogels. These findings suggest that silk fibroin-based hydrogels incorporating mesalazine and chitosan/TNF-α siRNA polyplex, produced via 3D bioprinting, hold promise as an effective therapeutic approach for IBD.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"213 ","pages":"Article 107252"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000086","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":"Predicting the adsorption behavior of olaparib on zinc oxide nanoparticles for improved pH-responsive drug delivery: experimental and DFT insights","authors":"Arwa Sultan Alqahtani ,&nbsp;Mahboubeh Pishnamazi","doi":"10.1016/j.ejps.2025.107253","DOIUrl":"10.1016/j.ejps.2025.107253","url":null,"abstract":"<div><div>The development of efficient drug delivery systems for hydrophobic anticancer drugs like Olaparib (OLA) remains a critical challenge in cancer therapy. This study presents a comprehensive investigation of OLA-loaded zinc oxide nanoparticles (OLA@ZnO) through integrated experimental and computational approaches to optimize pH-responsive drug delivery. ZnO nanoparticles were synthesized via a sol-gel method and characterized using SEM, XRD, FTIR, and UV–Vis spectroscopy, revealing successful OLA loading through Zn²⁺-carbonyl coordination and π-stacking interactions. The nanocomposites exhibited excellent colloidal stability (zeta potential = 11 mV at pH 7.4) and pH-triggered drug release, with 100 % release in 20 h (physiological pH) versus 90 % in 24 h (acidic pH). Korsmeyer-Peppas modeling confirmed diffusion-dominated release (<em>n</em> = 0.52) at neutral pH and erosion-controlled release (<em>n</em> = 0.69) in acidic conditions. Density functional theory (DFT) calculations revealed strong charge transfer, evidenced by a narrowed HOMO-LUMO gap (4.89 → 3.21 eV) and increased dipole moment (5.7 → 9.13 D). Molecular descriptors highlighted enhanced reactivity (softness = 0.621 eV⁻¹) and pH sensitivity (electrophilicity = 4.54 eV), while reduced density gradient (RDG) analysis visualized key binding interactions (−0.9 eV for Zn²⁺-<em>C</em> = <em>O</em> coordination). Thermodynamic analysis demonstrated spontaneous adsorption (ΔG = −0.77 to −0.89 eV) with exothermic behavior (ΔH = −0.87 to −1.00 eV) and entropy-driven release (ΔS = −0.00034 to −0.00037 eV/K). Size-dependent trends showed that smaller nanoparticles (0.9 nm) enabled rapid release (τ = 1.05 s) for acute therapy, while larger nanoparticles (2.0 nm) provided sustained delivery (τ = 152 s) for chronic treatment. These findings establish a robust structure-property relationship for designing tunable ZnO-based nanocarriers, offering a promising strategy to improve the therapeutic efficacy of OLA and other hydrophobic drugs in targeted cancer therapy.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107253"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000037","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}