European Journal of Pharmaceutical Sciences最新文献

{"title":"Individualized dosing strategies in breast cancer chemotherapy: Evidence for therapeutic drug monitoring-guided docetaxel treatment","authors":"Ya-Min Liu ,&nbsp;Wei Huang ,&nbsp;Yong-Zhe Tang ,&nbsp;Hai Zhang ,&nbsp;Sheng-Ying Qin ,&nbsp;Jin Zhang ,&nbsp;Jun-Wei Fan ,&nbsp;Rui-Zhuo Ouyang ,&nbsp;Hai-Ou Yang ,&nbsp;Xiao-Qing Zhang","doi":"10.1016/j.ejps.2025.107407","DOIUrl":"10.1016/j.ejps.2025.107407","url":null,"abstract":"<div><h3>Background</h3><div>Docetaxel is a first-line chemotherapy drug for breast cancer and is traditionally dosed based on body surface area (BSA). However, this method often leads to significant inter-patient variability and a high incidence of adverse drug reactions (ADRs). Therapeutic drug monitoring (TDM) offers a personalized dosing approach that may improve drug safety and efficacy. This study aimed to evaluate the clinical and pharmacoeconomic benefits of TDM-guided dosing compared to traditional BSA-based dosing in breast cancer patients receiving docetaxel-based chemotherapy.</div></div><div><h3>Methods</h3><div>A randomized controlled study was conducted at the Department of Breast Surgery, IPMCH, from October 2022 to July 2024. A total of 208 breast cancer patients were enrolled and randomly assigned to two groups: the BSA group (<em>n</em> = 104) and the TDM-guided pharmacokinetics (PK) group (<em>n</em> = 104). Adverse drug reactions—including hematological, gastrointestinal, skin, neurotoxic, and cardiotoxic events—were monitored and compared between groups. Liver function markers (ALT, AST, ALP) and pharmacoeconomic data (treatment-related costs) were also assessed. Statistical analyses included univariate and interaction models to evaluate the impact of dosing strategy on ADRs and costs.</div></div><div><h3>Results</h3><div>Patients in the TDM-guided PK group exhibited significantly lower levels of ALT, AST, and ALP, indicating reduced hepatic toxicity. Gastrointestinal ADRs—including nausea, diarrhea, and constipation—were less frequent and less severe in the PK group compared to the BSA group. Overall, the incidence and severity of ADRs were markedly reduced in the PK group. Pharmacoeconomic analysis demonstrated consistently lower treatment-related costs in the PK group. Both univariate and interaction analyses confirmed the clinical and economic benefits of TDM-guided dosing.</div></div><div><h3>Conclusion</h3><div>TDM-guided docetaxel dosing significantly reduced ADRs and improved cost efficiency in breast cancer chemotherapy. These findings support the implementation of TDM as a superior strategy to traditional BSA-based dosing, with potential to enhance both patient safety and healthcare resource utilization.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107407"},"PeriodicalIF":4.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741614","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":"Pharmacokinetic profile of dexamethasone in urine and plasma after single and multiple oral administration: Relevance to doping controls","authors":"Sergi Coll ,&nbsp;Claudia Bressan ,&nbsp;Núria Monfort ,&nbsp;Ana Aldea-Perona ,&nbsp;Marcel·lí Carbó ,&nbsp;Rosa Ventura","doi":"10.1016/j.ejps.2025.107405","DOIUrl":"10.1016/j.ejps.2025.107405","url":null,"abstract":"<div><div>Dexamethasone (DEX) is prohibited in sports competitions when administered by all injectable, oral or rectal routes, and is permitted at all times when administered by all other routes. The present work aimed to assess the urinary excretion profile of DEX after single and multiple oral administrations to verify the suitability of the new minimum reporting level (MRL) of 60 ng/mL established by the World Anti-Doping Agency to distinguish allowed and prohibited administrations. Moreover, the minimum washout period of three days established for out-of-competition treatments with oral glucocorticoids will be evaluated.</div><div>DEX was administered to healthy volunteers using two different oral treatments: single administration (4 mg, <em>n</em> = 8 male volunteers) and multiple administrations (2 mg/12 h for 5 days, <em>n</em> = 8 male volunteers). Urine and plasma samples collected before and after administration were analysed using liquid chromatography-tandem mass spectrometry. DEX and 6β‑hydroxy-DEX, were the predominant compounds detected in urine, with peak urinary excretion observed within the first 4 h post-dose. DEX concentrations exceeded the new MRL mainly within 12 h after a single dose, with one volunteer showing levels above this threshold up to 24–36 h. In the multiple-dose study, most of the DEX concentrations remained above 60 ng/mL after the second dose and throughout the dosing period and declined quickly after the final dose. Plasma DEX kinetics was defined by an open bicompartmental model with a first order oral absorption. DEX was detectable up to 48 h post-administration. In the multiple dose study, the steady-state concentrations were reached soon after the first dose, and DEX showed no evidence of accumulation. CORT levels decreased rapidly after both single and multiple administrations due to suppression of the hypothalamic-pituitary-adrenal axis. Recovery times varied among volunteers.</div><div>The MRL of 60 ng/mL proved appropriate for distinguishing permitted from prohibited use with a 3-day washout, though further studies on non-systemic routes are recommended to refine sensitivity.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107405"},"PeriodicalIF":4.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721647","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":"Update on clinical trials of intra-articular disease-modifying osteoarthritis drugs inducing cartilage regeneration","authors":"Luca Morici ,&nbsp;Ines Nikolic","doi":"10.1016/j.ejps.2025.107403","DOIUrl":"10.1016/j.ejps.2025.107403","url":null,"abstract":"<div><div>Osteoarthritis is the most common degenerative joint disease affecting millions of people in the world and leading to disability. Currently, the only available treatments on the market are symptomatic therapies for pain and inflammation. There are no intra-articular drugs that can restore the cartilage matrix, also known as disease-modifying osteoarthritis drugs (DMOADs). This review focuses on all clinical trials of pro-anabolic DMOADs, which stimulate the regeneration of the cartilage matrix by inducing the differentiation of mesenchymal progenitors into chondrocytes, a process known as chondrogenesis. This review also discussed some pathways of chondrocytes, which boost the transcription of genes involved in the production of extracellular matrix components. Finally, the review also covers some implants in the commercial and clinical phases for cartilage repair.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107403"},"PeriodicalIF":4.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721731","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":"Mechanistic insights into semi-solid extrusion 3D printing of indomethacin-nicotinamide cocrystal-loaded oral fast-dissolving films","authors":"Maha F. Emam ,&nbsp;Elina Harju ,&nbsp;Atte Junnila ,&nbsp;Kirsi Mikkonen ,&nbsp;Teemu Tomberg ,&nbsp;Clare Strachan ,&nbsp;Anssi-Pekka Karttunen ,&nbsp;Leena Peltonen","doi":"10.1016/j.ejps.2025.107404","DOIUrl":"10.1016/j.ejps.2025.107404","url":null,"abstract":"<div><div>The growing demand for personalized medicine requires adaptable dosage forms capable of addressing challenges associated with poorly soluble drugs. Cocrystals offer a powerful strategy to enhance solubility, while semi-solid extrusion (SSE) 3D printing enables flexible, patient-tailored manufacturing. This study establishes a systematic framework for developing oral fast-dissolving films (OFDFs) incorporating indomethacin–nicotinamide (IND–NIC) cocrystals using SSE 3D printing. Critical Material Attributes (CMAs), HPMC–glycerol base, sodium starch glycolate (SSG), and varying cocrystal loadings, were systematically adjusted to evaluate their influence on key ink and film Critical Quality Attributes (CQAs).</div><div>All inks displayed desirable shear-thinning behaviour, with IND–NIC cocrystals and SSG synergistically reinforcing the structural network for reliable extrusion and shape fidelity. Solid-state analyses (XRPD, DSC, PLM, Raman microscopy) confirmed preservation of the cocrystal form throughout ink preparation, printing, and short-term storage. The 3D printed OFDFs exhibited uniform thickness, weight, and drug content with minimal variability across batches, and displayed humidity-dependent mechanical behaviour that varied with cocrystal loading.</div><div>All formulations achieved rapid drug release, exceeding 80 % IND dissolution within 30 min. Dissolution profiles were consistent across cocrystal loadings and remained statistically equivalent for films printed from inks stored for up to 2 days, as well as for the 3-day redispersed ink, confirming that the structural reinforcement required for printability does not compromise rapid release performance.</div><div>Overall, this work provides mechanistic insight into the formulation–process–performance relationships governing SSE 3D printing of cocrystal-loaded OFDFs and highlights the potential of this green, low-temperature platform for decentralized, patient-centric manufacturing of fast-dissolving dosage forms.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107404"},"PeriodicalIF":4.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721582","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":"The relationship between PDE4 and AQP5 in lung tissue under inflammatory conditions: An experimental study","authors":"Ayse Bozkurt ,&nbsp;Zafer Bayraktutan ,&nbsp;Erdem Toktay ,&nbsp;Adem Kara ,&nbsp;Zekai Halici ,&nbsp;Elif Cadirci","doi":"10.1016/j.ejps.2025.107400","DOIUrl":"10.1016/j.ejps.2025.107400","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to examine the relationship between Phosphodiesterase 4 (PDE4) and Aquaporin-5 (AQP5) under Lipopolysaccharide (LPS) induced-inflammatory condition.</div></div><div><h3>Methods</h3><div>Inflammatory Acute lung injury (ALI) was induced by intratracheal LPS (5 mg/kg) administration. Rolipram (intraperitoneal) was used as PDE4 inhibiting agent at three different doses (1, 3 and 5 mg/kg) in rat groups. 24 h after LPS administration lung tissues obtained and following analyses performed. AQP5, Phosphodiesterase 4D (PDE4D), Cyclic adenosine monophosphate (cAMP) levels were evaluated for determination of the relationship between these parameters. Also Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), Nuclear factor kappa B (NF-κB), Mitogen-activated protein kinase (MAPK) levels were evaluated as ALI markers.</div></div><div><h3>Results</h3><div>LPS-induced ALI resulted in increased PDE4 enzyme and inflammatory marker levels (IL-6, TNF-α, NF-κB and MAPK) and decreased AQP5 and cAMP levels. Inhibition of PDE4 enzyme to increase cAMP levels by Rolipram resulted in increased AQP5 expression and decreased inflammatory condition and in lung tissues. These results were supported by histopathological and immunhistochemical results.</div></div><div><h3>Conclusion</h3><div>The fact that this study observed a decreases PDE4 expression and increases in AQP5 expression upon Rolipram administration might indicate a close relationship of these two parameters in inflammatory lung disease.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107400"},"PeriodicalIF":4.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721652","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":"Protective effects of SA-31 in a psychostimulant-induced neurotoxicity model using SH-SY5Y cells","authors":"Charles E. Amankwa ,&nbsp;Biddut DebNath ,&nbsp;Arlene Abraham ,&nbsp;Olivia Young ,&nbsp;Sudershan R Gondi ,&nbsp;Michael J Forster ,&nbsp;Ritu A. Shetty ,&nbsp;Suchismita Acharya","doi":"10.1016/j.ejps.2025.107399","DOIUrl":"10.1016/j.ejps.2025.107399","url":null,"abstract":"<div><h3>Background</h3><div>Cocaine- and methamphetamine (METH)-induced mitochondrial dysfunction and oxidative stress are key contributors to the neuropathology of psychostimulant addiction. These effects are often accompanied by epigenetic alterations, mitochondrial damage, and the accumulation of reactive oxygen species (ROS). Methionine synthase (MS) plays a critical role in epigenetic regulation and neuronal survival and may offer neuroprotection against psychostimulant-induced toxicity. We hypothesize that SA-31, a novel thiourea-based analog of TEMPOL, will attenuate cocaine or METH induced decrease in antioxidant, anti-inflammatory, and MS activities in neuronal cells.</div></div><div><h3>Methods</h3><div>SA-31 was synthesized and characterized via ¹H NMR and mass spectrometry. Human SH-SY5Y dopaminergic neural cells were exposed to tert‑butyl hydrogen peroxide (TBHP), cocaine hydrochloride, or methamphetamine (METH), with or without co-treatment with SA-31 for 24 h. Cell viability was measured using MTT assays. MS activity, IL-1β, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase levels were assessed via ELISA. Mitochondrial function was evaluated using Seahorse-based oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) assays.</div></div><div><h3>Results</h3><div>SA-31 (10–100 µM) significantly protected cells from TBHP-, cocaine-, and METH-induced cytotoxicity. TBHP and METH reduced MS activity, which was significantly restored by SA-31. The compound also reversed cocaine-induced reductions in SOD, GPx, and catalase and lowered pro-inflammatory IL-1β levels. Additionally, SA-31 (1–100 µM) enhanced mitochondrial respiration and glycolytic activity.</div></div><div><h3>Conclusion</h3><div>These findings suggest that SA-31 confers neuroprotection by enhancing MS activity, upregulating antioxidant defenses, and improving mitochondrial function. Further studies in rodent models of addiction are planned to evaluate its therapeutic potential for psychostimulant use disorders and related neurodegenerative conditions.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107399"},"PeriodicalIF":4.7,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713845","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":"High-throughput screening of amorphous solid dispersions: a systematic approach to enhance bioaccessibility of a poorly soluble drug","authors":"Malte Bøgh Senniksen ,&nbsp;Justus Johann Lange ,&nbsp;Wiebke Saal ,&nbsp;Patrick O’Dwyer ,&nbsp;Martin Kuentz ,&nbsp;Brendan T. Griffin ,&nbsp;Susanne Page ,&nbsp;Jennifer Dressman ,&nbsp;Nicole Wyttenbach","doi":"10.1016/j.ejps.2025.107401","DOIUrl":"10.1016/j.ejps.2025.107401","url":null,"abstract":"<div><div>Poor aqueous solubility and thereby poor and/or variable bioavailability of drug candidates is frequently overcome by developing enabling formulations such as amorphous solid dispersions (ASDs). This study proposes a systematic, miniaturized approach to evaluate the ASD developability of an active pharmaceutical ingredient (API) based on i) assessment of glass forming ability ii) assessment of the supersaturation potential of the neat API by supersaturation/permeation testing, iii) selection of an appropriate ASD carrier system using high-throughput dissolution screening of ASD films and iv) performing high-throughput dissolution/permeation testing of ASD films. The model drug candidate, RO6897779, exhibited good glass forming ability. Eight pharmaceutical polymers (CAP, Eudragit® E, Eudragit® L100, HPMC 100LV, HPMCAS-M, PVP K25, PVP VA64, and Soluplus®) were screened as ASD carriers by high-throughput dissolution testing at drug loads of 20, 30 and 40 % [w/w]. Due to poor performance of the binary systems, ternary ASDs containing Soluplus® were prepared at surfactant loads of 4, 6 and 8 % [w/w] and subsequently, high-throughput dissolution/permeation studies were conducted on selected compositions. The composition containing RO6897779 at a drug load of 20 % in Soluplus®[w/w] with the addition of 6 % [w/w] SDS yielded the best performance, but was inferior to the permeation of supersaturated neat RO6897779. Further studies should be conducted to assess the ability of this four-step, miniaturized approach to predict optimal ASD formulations over a broad range of API physicochemical properties.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107401"},"PeriodicalIF":4.7,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707092","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":"Longitudinal monitoring of nanofibrillar cellulose hydrogel medical implants in mice using positron emission tomography","authors":"Xiaoqing Zhuang ,&nbsp;Jenni Virta ,&nbsp;Heidi Liljenbäck ,&nbsp;Lauri Paasonen ,&nbsp;Anu J. Airaksinen ,&nbsp;Anne Roivainen ,&nbsp;Xiang-Guo Li","doi":"10.1016/j.ejps.2025.107402","DOIUrl":"10.1016/j.ejps.2025.107402","url":null,"abstract":"<div><div>Nanofibrillar cellulose (NFC) hydrogel has emerged as a promising implantable material for therapeutic applications. In this study, the relatively longer-lived positron-emitting radionuclide zirconium-89 was chelated to the octadentate deferoxamine (DFO*)-conjugated NFC hydrogel ([⁸⁹Zr]Zr-DFO*-NFC) to enable longitudinal monitoring of its <em>in vivo</em> fate using positron emission tomography techniques. Following subcutaneous implantation in healthy mice, [⁸⁹Zr]Zr-DFO*-NFC retained radioactivity at the implant site for at least 14 days, with minimal signal detected in the kidneys, urinary bladder, and overlying skin. In contrast, mice receiving a control formulation of [⁸⁹Zr]Zr-oxalate mixed with NFC hydrogel showed progressive accumulation of radioactivity in the bones, consistent with known [⁸⁹Zr]Zr-oxalate distribution patterns, and only limited retention at the implant site by Day 7. These findings demonstrate that [⁸⁹Zr]Zr-DFO*-NFC hydrogel implants exhibit high <em>in vivo</em> stability with negligible systemic release following subcutaneous implantation, supporting their potential use as safe and traceable biomaterial platforms.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107402"},"PeriodicalIF":4.7,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707293","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-functionalized mesoporous silica nanoparticles for topical axitinib delivery to the posterior eye segment","authors":"Li Xu ,&nbsp;Zih-An Chen ,&nbsp;Cheng-Hsun Wu ,&nbsp;Yi-Ping Chen ,&nbsp;Si-Han Wu ,&nbsp;Chung-Yuan Mou ,&nbsp;Ching-Li Tseng ,&nbsp;Yueh Chien ,&nbsp;Hardy Wai-Hong Chan ,&nbsp;Tien-Chun Yang ,&nbsp;Shih-Hwa Chiou","doi":"10.1016/j.ejps.2025.107398","DOIUrl":"10.1016/j.ejps.2025.107398","url":null,"abstract":"<div><div>Topical drug delivery to the posterior eye segment remains a significant challenge due to ocular anatomical barriers, particularly in diseases such as wet age-related macular degeneration (AMD), where treatment typically relies on frequent intravitreal (IVT) injections of anti-angiogenic agents. In this study, we present a non-invasive eye drop formulation of axitinib (AXT), a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, encapsulated within 25-nm dual-functionalized mesoporous silica nanoparticles (AXT@dual-MSNs) engineered for efficient retinal delivery. The nanoparticles feature sulfonate-functionalized mesopores that enhanced AXT loading and solubilization, along with a PEGylated/quaternary ammonium-modified surface that improved colloidal stability and favored intramesopore drug confinement. Following topical administration, AXT@dual-MSNs achieved retinal accumulation via the conjunctiva-sclera-choroid pathway, effectively bypassing the corneal route. A pharmacokinetic analysis confirmed rapid, transscleral delivery of AXT with therapeutically relevant concentrations in the retina. In a laser-induced choroidal neovascularization (CNV) mouse model, a well-established surrogate for wet AMD, AXT@dual-MSN eyedrops significantly suppressed neovascular lesion formation, outperforming free-drug eyedrops and IVT AXT injection. Notably, the formulation exhibited excellent ocular tolerance, with no evidence of local toxicity or contralateral eye exposure. This work introduces a novel nanocarrier system capable of overcoming the longstanding delivery barrier to the posterior eye segment via eyedrops, offering a safe, effective, and clinically translatable alternative to IVT injections. The modular design of AXT@dual-MSNs also holds promise for expanding topical access to other hydrophobic or labile therapeutics targeting retinal diseases.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107398"},"PeriodicalIF":4.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700086","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":"Development and optimization of Soluplus®/Pluronic-based polymeric micelles for bicalutamide delivery: characterization, lyophilization, stability, and cellular studies","authors":"Nihal Tugce Ozaksun ,&nbsp;Tugce Tayyar ,&nbsp;Aysun Ozdemir ,&nbsp;Mustafa Ark ,&nbsp;Tuba Incecayir","doi":"10.1016/j.ejps.2025.107395","DOIUrl":"10.1016/j.ejps.2025.107395","url":null,"abstract":"<div><div>Polymeric micelles are promising nanocarriers for improving the solubility and therapeutic efficacy of poorly water-soluble drugs. In this study, bicalutamide (BIC)-loaded polymeric micelles were developed and optimized using central composite design (CCD) by varying two formulation factors: the Soluplus® percentage (%) and the Pluronic F127/Pluronic F68 ratio (w/w). The selected formulations exhibited favorable physicochemical properties with particle size (PS) below 100 nm, low polydispersity index (PDI) (≤ 0.066), and high encapsulation efficiencies (EE) (up to 90.6 %). Transmission electron microscopy (TEM) confirmed the spherical and monodisperse structure. The micelles exhibited near-neutral zeta potentials. Lyophilization with trehalose did not significantly alter particle size or uniformity<em>. In vitro</em> release studies demonstrated sustained drug release profiles for 72 h, and <em>in vitro</em> solubility measurements revealed a significant increase (∼161 to 335-fold) compared to free BIC. The formulations also remained colloidally stable upon dilution and were physically stable for up to 6 months at 4 °C, 25 °C/60 % Relative Humidity (RH), and 40 °C/75 % RH. Cellular uptake studies in the human prostate cancer (PC-3) cell line confirmed effective internalization of the micelles. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays demonstrated a concentration- and time-dependent cytotoxicity. F7 exhibited superior cytotoxicity among the tested formulations, compared to free BIC, while its blank formulation showed no significant toxicity, indicating favorable biocompatibility. These results suggest that the developed polymeric micelle systems have potential as stable and biocompatible delivery systems for BIC, warranting further investigation.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107395"},"PeriodicalIF":4.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700073","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}