European Journal of Pharmaceutical Sciences最新文献

{"title":"A dual-strategy nanocomposite hydrogel platform of nanosuspensions and deformable liposomes for enhanced curcumin delivery against skin cancer cells","authors":"Khin Cho Aye ,&nbsp;Supusson Pengnam ,&nbsp;Boonnada Pamornpathomkul ,&nbsp;Thapakorn Charoenying ,&nbsp;Prasopchai Patrojanasophon ,&nbsp;Praneet Opanasopit ,&nbsp;Chaiyakarn Pornpitchanarong","doi":"10.1016/j.ejps.2025.107373","DOIUrl":"10.1016/j.ejps.2025.107373","url":null,"abstract":"<div><div>Patient outcomes in skin cancer are compromised by invasive treatments, demanding a paradigm shift toward effective, non-invasive strategies. This study aimed to develop dual-strategy nanocomposite hydrogel platforms for enhanced, localized delivery of curcumin against skin cancer cells. Two distinct nanocarriers, curcumin nanosuspensions (CUR-Ns) and curcumin liposomes (CUR-Lip), were engineered and embedded within a bioadhesive Gantrez™/gelatin hydrogel. Anticancer activity, cellular uptake, and apoptosis induction were assessed in A431 skin cancer cell line. Nanocomposite hydrogels were fabricated by EDC/NHS crosslinking, with nanocurcumin pre-mixed in gelatin to ensure uniform dispersion. <em>Ex vivo</em> skin permeation was evaluated using Franz diffusion cells with neonatal porcine skin. Both formulations demonstrated potent anticancer activity against A431 cells, with CUR-Lip (IC₅₀ = 9.32 µg/mL) and CUR-Ns (IC₅₀ = 13.43 µg/mL) dramatically outperforming free CUR (IC₅₀ = 44.73 µg/mL) while maintaining excellent biocompatibility. Physicochemical characterizations of the hydrogel demonstrated high moisture content, fluid absorbency, and adequate mechanical strength. These favorable properties facilitated effective delivery. Crucially, the nanocarriers displayed unique therapeutic kinetics. CUR-Ns provided a rapid onset of action, characterized by faster initial skin permeation. In contrast, CUR-Lip offered superior sustained efficacy, showing greater cytotoxicity, and achieving significantly higher cumulative skin deposition, with a transdermal flux of 105.52 ng/cm²/h. The hydrogel platform successfully preserved these distinct permeation profiles, confirming its utility as a versatile delivery vehicle. This dual-strategy approach enables tailored curcumin delivery offering either rapid or sustained release and represented a significant advancement in developing non-invasive therapies for skin cancer.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107373"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488149","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":"ASGPR-targeted micelles co-delivering lenvatinib and COP1 siRNA for hepatocellular carcinoma via dual-targeting","authors":"Kailibinuer Aobuliaisan ,&nbsp;Qian Li ,&nbsp;Chengcheng Deng,&nbsp;Feng Yang,&nbsp;Zhi Xie,&nbsp;Wenyan Jia,&nbsp;Dongfeng Yin","doi":"10.1016/j.ejps.2025.107308","DOIUrl":"10.1016/j.ejps.2025.107308","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) therapy faces significant challenges including poor drug bioavailability and limited gene delivery efficiency. This study developed N-acetylgalactosamine (GalNAc)-functionalized polymeric micelles co-loaded with Lenvatinib (LFT) and small interfering RNA (siRNA) targeting E3 ligase COP1 (RFWD2) (GalNAc@LFT/siRNA-MMs) for the co-delivering of LFT and COP1 siRNA. This combinatory strategy aims to enhance HCC treatment by simultaneously enabling chemotherapy and gene silencing. The nanoplatform was constructed using low-molecular-weight polyethyleneimine (PEI) cross-linked with Pluronic copolymers and surface-modified with GalNAc for asialoglycoprotein receptor (ASGPR)-mediated targeting. Physicochemical characterization revealed spherical nanoparticles (∼187 nm; PDI ∼0.41) with sustained drug release properties. In vitro studies demonstrated preferential uptake in ASGPR-positive HCC cells with enhanced cytotoxicity through apoptosis induction and S-phase cell cycle arrest. COP1 silencing was confirmed at both mRNA and protein levels, sensitizing HCC cells to LFT treatment. In an orthotopic HCC model (<em>n</em> = 5 mice/group), GalNAc@LFT/siRNA-MMs exhibited superior tumor targeting and remarkable antitumor efficacy (73% tumor reduction versus 31% with free LFT). Immunohistochemical (IHC) analysis revealed comprehensive tumor suppression through reduced proliferation (Ki-67), inhibited angiogenesis (CD31), and enhanced apoptosis (Caspase-3), while maintaining excellent biocompatibility. This rationally designed co-delivery system overcomes key limitations of conventional HCC therapy by integrating targeted delivery with combined therapeutic actions, offering a promising approach for improving treatment outcomes in this challenging malignancy.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107308"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228547","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":"Effect of amino acids on the compaction behavior and stability of spray-dried trypsin/lactose powder","authors":"Chengqian Zhang ,&nbsp;Göran Frenning ,&nbsp;Marco van de Weert ,&nbsp;Simon Bjerregaard ,&nbsp;Jukka Rantanen ,&nbsp;Mingshi Yang","doi":"10.1016/j.ejps.2025.107358","DOIUrl":"10.1016/j.ejps.2025.107358","url":null,"abstract":"<div><div>Amino acids (AAs) have been employed as excipients in spray-dried (SD) protein formulations due to their stabilizing effects and particle engineering abilities. However, the research focusing on the influence of AAs on the tabletability of SD protein powders is still limited. The aim of this study was to investigate the effects of five diverse AAs, arginine hydrochloride (Arg·HCl), leucine (Leu), glycine (Gly), tryptophan (Trp) and sodium aspartate (Asp·Na), on the compaction behavior and stability of SD trypsin/lactose powders. The SD powders were characterized in terms of morphology, bulk powder properties, residual moisture content, and solid-state structure. Subsequently, the resulting powder compacts were characterized with respect to compressibility, compactability, and tabletability. Lastly, the conformational stability and enzymatic activity of trypsin in different SD formulations after compaction were assessed. The results showed that the SD trypsin/lactose/Arg·HCl powder exhibited the poorest tabletability. Moreover, SD trypsin/lactose/Leu powder showed relatively poor tabletability, while SD trypsin/lactose/Trp powder showed a moderate tabletability. On the other hand, SD trypsin/lactose/Gly powder displayed the best compressibility, and the SD trypsin/lactose/Asp·Na tablets exhibited the highest tensile strengths at high compaction pressures. However, an altered conformation and reduced enzymatic activity of trypsin were observed in the SD trypsin/lactose/Asp·Na formulation upon compaction. In conclusion, the addition of five different AAs to the SD trypsin/lactose powder system resulted in distinct compaction behaviors and stabilizing effects, which can be attributed to the intrinsic properties of the original SD particles, such as hygroscopicity, morphology, and potential AAs' surface distribution.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107358"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430644","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 influence of dapagliflozin on diabetic ocular complications: An observational cohort study","authors":"Jo-Hsin Chen ,&nbsp;Fei-Hung Hung ,&nbsp;Yu-Ting Wang ,&nbsp;Jin-Hua Chen ,&nbsp;Shu-Fen Liao ,&nbsp;Chun-Mei Hsueh ,&nbsp;Jong-Shiuan Yeh ,&nbsp;Gregory Y.H. Lip","doi":"10.1016/j.ejps.2025.107382","DOIUrl":"10.1016/j.ejps.2025.107382","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to evaluate the risk of developing ocular outcomes, including diabetic retinopathy (DR), open-angle glaucoma (OAG), and visual loss, in patients with type 2 diabetes mellitus (T2DM) treated with dapagliflozin, a sodium glucose cotransporter 2 inhibitor (SGLT2i), compared to those receiving other hypoglycemic agents.</div></div><div><h3>Methods</h3><div>This was an observational, retrospective, multi-center cohort study using data from the Taipei Medical University Clinical Research Database (2016–2020). Participants included 18,854 newly diagnosed T2DM patients with an estimated glomerular filtration rate above 45 ml/min/m². After excluding those with a history of DR, OAG, or visual loss, 1400 dapagliflozin users and 1400 non-SGLT2i users were matched using 1:1 propensity score matching. The primary outcome was the composite incidence of DR, OAG, or visual loss.</div></div><div><h3>Results</h3><div>After 1-year follow-up, dapagliflozin users had a significantly lower incidence of DR, OAG, or visual loss (2.78 % vs. 5.35 %; adjusted hazard ratio [aHR], 0.53; 95 % CI, 0.36–0.79, <em>p</em> = 0.002). At the 2-year follow-up, the incidence was 3.85 % in dapagliflozin users compared to 6.35 % in non-SGLT2i users (aHR, 0.63; 95 % CI, 0.44–0.88, <em>p</em> = 0.007).</div></div><div><h3>Conclusions</h3><div>Dapagliflozin was associated with a significantly lower incidence of DR, OAG, or visual loss in newly diagnosed T2DM patients within five years, suggesting its potential benefit in preventing ocular complications.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107382"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556523","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":"Application of artificial neural network to determine optimum formulation development and in vitro characterization of methylene blue and galantamine loaded polymeric nanoparticles for the treatment of Alzheimer’s disease","authors":"Busra Ozturk ,&nbsp;Huriye Demir ,&nbsp;Mine Silindir-Gunay ,&nbsp;Yagmur Akdag ,&nbsp;Selma Sahin ,&nbsp;Tugba Gulsun","doi":"10.1016/j.ejps.2025.107364","DOIUrl":"10.1016/j.ejps.2025.107364","url":null,"abstract":"<div><div>Alzheimer's disease is a major neurodegenerative disorder characterized by complex pathophysiology and currently lacks a curative treatment. This study aims to develop and characterize methylene blue and galantamine co-loaded PLGA nanoparticles, surface-modified with poloxamer 188 and GSH, to increase blood residence time and improve brain-targeted delivery. The nanoparticles were prepared using the double emulsion solvent evaporation method, and their physicochemical properties were characterized by TEM, FT-IR, DSC, XRD, and ¹³C NMR. Artificial neural network modeling was used to optimize the formulation parameters, including PLGA %, PVA %, and sonication time, for predicting particle size and encapsulation efficiencies of methylene blue and galantamine. Results showed that the optimized nanoparticles had particle sizes &lt;200 nm, appropriate zeta potential, and high encapsulation efficiencies. DSC, FT-IR, XRD, and NMR analyses confirmed the absence of crystalline peaks for methylene blue and galantamine, indicating successful encapsulation. Artificial neural network models demonstrated high predictive accuracy, serving as a valuable tool for formulation optimization. This dual-drug, surface-modified nanoparticle approach offers promising potential for multi-target therapy in Alzheimer's disease.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107364"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458028","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":"A risk-based, QTPP-driven framework for semi-solid extrusion 3d printing of personalized medicines: Integrating hospital compounding and clinical trial regulation","authors":"Maxime Annereau ,&nbsp;Philippe-Henri Secretan ,&nbsp;Bernard Do","doi":"10.1016/j.ejps.2025.107340","DOIUrl":"10.1016/j.ejps.2025.107340","url":null,"abstract":"<div><div>Semi-solid extrusion (SSE) 3D printing enables precise, patient-specific oral medicines, yet its uptake is constrained by fragmented regulatory pathways. This study develops an applied, risk-based framework grounded in empirical data from hospital compounding and early-phase clinical trial implementation, integrating both within a unified regulatory model through the concept of the printable ink as a pharmaceutical intermediate.</div><div>Drawing from three pediatric use cases involving 5 different active pharmaceuticals ingredients (APIs), trimethoprim-sulfamethoxazole (Bactrim®), cyclophosphamide, tamoxifen (OPERA clinical trial) and isoleucine (Maple syrup urine disease) the framework applies quality-by-design principles (ICH Q8–Q11, USP &lt;1220&gt;) to define critical quality attributes (CQAs), critical process parameters (CPPs), and in-process controls (IPCs) suitable for both centralized and point-of-care production. Two complementary tables stratify APIs by risk and map them to actionable quality control strategies, enabling science-based decisions on when IPCs alone suffice versus when full GMP oversight is required.</div><div>This harmonized model supports reproducible, traceable production across decentralized sites, addressing regulatory ambiguity while preserving flexibility for innovation in paediatric and rare disease care.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107340"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344251","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":"Investigating retention time and fluid dynamics of the vehicles in non-invasive topical ocular drug delivery systems","authors":"Zahra Ghaemmaghamian ,&nbsp;Akbar Davoodi ,&nbsp;Carsten Svaneborg ,&nbsp;Anders Højslet Vestergaard ,&nbsp;René Holm","doi":"10.1016/j.ejps.2025.107369","DOIUrl":"10.1016/j.ejps.2025.107369","url":null,"abstract":"<div><div>Efficient topical ocular drug delivery is critical for managing eye diseases, yet non-invasive approaches often suffer from limited retention time and low bioavailability. This study evaluated the retention time and spatial distribution of I-Drop MGD artificial tear, using Anterior segment Optical Coherence Tomography (ASOCT). Twelve healthy volunteers were enrolled, each assessed in both eyes across four visits, yielding a dense, paired dataset with high statistical power and reduced inter-subject variability.</div><div>Baseline assessments showed a strong correlation between the central corneal thickness (CCT) measurements in fellow eyes and minimal variability across visits. Following instillation, CCT increased sharply and then decayed over time, consistent with tear film clearance. Retention time, estimated by exponential fitting, had a mean of 13. 94 ± 16.32 minutes and a median of 7.7 minutes (3.4–16.78 minutes). Qualitative image analysis revealed that thinner, well-distributed films cleared more slowly than thicker accumulations, suggesting that film morphology influenced drainage dynamics. Although the administration volume was fixed, differences in ocular surface area, due to natural variation in anatomy, appeared to affect the distribution of the formulation and, consequently, retention behavior.</div><div>Statistical analyses further demonstrated that neither blinking rate nor tear film break-up time (TBUT), within physiological ranges, significantly impacted retention time for healthy subjects. Similarly, subjective discomfort levels reported after installation had no measurable effect. Statistical power analysis confirmed that the paired-eye, multi-visit design was robust, requiring as few as four subjects to detect treatment effects with approximately 81 % power based upon the tested eye drops.</div><div>Overall, the findings supported the use of ASOCT for high-resolution, non-invasive assessment of ocular formulation retention and suggested that future design of ophthalmic vehicles should account for film-distribution behavior and rheological properties to optimize performance.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107369"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476821","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":"Assessment of pulmonary delivery efficacy of archaeal tetraether lipids based ICG- and DiR-loaded liposomes for antitumoral photodynamic therapy","authors":"Rashid Munir ,&nbsp;Lisa Schöne ,&nbsp;Aman Ullah,&nbsp;Konrad Engelhardt,&nbsp;Eduard Preis,&nbsp;Jens Schäfer,&nbsp;Muhammad Umair Amin,&nbsp;David Schorr,&nbsp;Ibrahim Awak,&nbsp;Anam Sajjad Khan,&nbsp;Ayesha Ishfaq,&nbsp;Raneem Ahmad,&nbsp;Udo Bakowsky","doi":"10.1016/j.ejps.2025.107362","DOIUrl":"10.1016/j.ejps.2025.107362","url":null,"abstract":"<div><div>Lung cancer remains a leading cause of cancer-related deaths worldwide, highlighting the urgent need for novel therapeutic strategies, whereby pulmonary delivery offers a more promising approach, as it delivers the therapeutic moiety directly to the lungs, reducing systemic toxicity. Among emerging novel treatment strategies, photodynamic therapy (PDT) has emerged as a minimally invasive approach for treating various diseases, including lung cancer. However, the practical application of photosensitizers remains challenging due to their poor stability and limited availability at the targeted site. In this study, archaeal tetraether lipid (TEL)-based liposomes were developed to encapsulate indocyanine green (ICG) and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR), two near-infrared (NIR) fluorescent photosensitizers, for inhalable, lung-targeted PDT. Liposomes were prepared using the thin-film hydration method with a lipid composition of 1,2-dipalmitoyl-sn‑glycero-3-phosphocholine (DPPC), cholesterol (Chol), and hydrolyzed glycerol dialkyl nonitol tetraether (hGDNT) in a molar ratio of 85:10:5 and DPPC, Chol, and polar lipid fraction E (PLFE) in a molar ratio of 85:10:5. Physicochemical characterization demonstrated that both hGDNT- and PLFE-based liposomes were in the nanometer size range with good monodispersity. Compared to hGDNT-liposomes, PLFE-based formulations were generally smaller, more uniform, and exhibited greater surface charge stability. All formulations exhibited excellent colloidal stability for up to two weeks (14 days), maintaining their physicochemical characteristics both during storage and after aerosolization using a vibrating-mesh nebulizer. A spherical nanoscale morphology was revealed by atomic force microscopy (AFM). Alterations in membrane properties induced by the incorporation of the drug were highlighted by phase imaging, confirming successful encapsulation and structural modulation, whereas transmission electron microscopy (TEM) revealed the unilamellarity of the liposomal formulations. PDT assessment on A549 cells revealed that DiR-loaded hGDNT-lipsomes (DiR-hGDNT-LPs) exhibited greater phototoxicity with a 50 % inhibitory concentration (IC₅₀) of 9.65 µg/mL, compared to 16.45 µg/mL for ICG-loaded-hGDNT-liposomes (ICG-hGDNT-LPs) upon NIR irradiation. Confocal laser scanning microscopy analysis demonstrated that DiR-hGDNT-LPs and ICG-hGDNT-LPs were efficiently taken up by A549 cells, with fluorescence predominantly localized in the cytoplasm, indicating effective intracellular retention. Intracellular reactive oxygen species (ROS) generation was confirmed using the 2′,7′-dichlorofluorescin diacetate assay, which exhibited strong light-dependent ROS production upon NIR radiation. These results suggest that TEL liposomes are highly stable, efficient nanocarriers that enhance the therapeutic potential of photosensitizers for non-invasive lung-targeted PDT.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107362"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451292","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 yeast cell wall incorporation on the mucoadhesion, stability, oral permeability and release profile of alginate/whey protein beads loaded with insulin","authors":"Emmanuelle Lainé ,&nbsp;Valerie Hoffart ,&nbsp;Imen Dhifallah ,&nbsp;Ghislain Garrait ,&nbsp;Eric Beyssac","doi":"10.1016/j.ejps.2025.107385","DOIUrl":"10.1016/j.ejps.2025.107385","url":null,"abstract":"<div><div>This study aimed to evaluate the impact of incorporating yeast cell wall (YCW) into alginate/whey protein (ALG/WP) particles as a strategy to improve oral insulin delivery. Insulin-loaded particles were produced by an extrusion–gelation process with or without YCW, and their physicochemical, mucoadhesive, and permeability properties were assessed <em>in vitro, ex vivo</em>, and <em>in vivo</em>. The inclusion of YCW increased the viscosity of the polymeric solution, resulting in more cohesive particles and a significant reduction in insulin loss during coating. Encapsulation efficiencies ranged from 65 to 99%. However, YCW did not significantly affect particle size or the release mechanism, which remained diffusion-controlled. Although YCW-containing beads exhibited enzyme inhibitory and mucoadhesive properties, insulin protection against enzymatic degradation was similar to that of control beads. YCW moderately enhanced insulin permeability in Caco-2 cell monolayers without cytotoxicity, consistent with a reversible reduction of transepithelial electrical resistance. This effect did not translate into a measurable increase in insulin absorption in ex vivo duodenum or <em>in vivo</em> duodenal administration, indicating that its contribution as an absorption enhancer is limited under physiologically complex conditions.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107385"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573337","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":"Pulmonary delivery of siRNA lipoplexes and lipid nanoparticles using a vibrating mesh nebuliser","authors":"Michael T. Neary ,&nbsp;Lianne M. Mulder ,&nbsp;Ciaran O. Leime ,&nbsp;Ronan MacLoughlin ,&nbsp;Brunella Grassiri ,&nbsp;Łukasz Baranowski ,&nbsp;Piotr S. Kowalski ,&nbsp;Abina M. Crean ,&nbsp;Katie B. Ryan","doi":"10.1016/j.ejps.2025.107386","DOIUrl":"10.1016/j.ejps.2025.107386","url":null,"abstract":"<div><div>Inhalation via nebulisation is a promising method to deliver high concentrations of siRNA to the lung epithelium in a direct and non-invasive manner for the treatment of numerous respiratory-related illnesses. However, nebulisation can be destructive towards siRNA nanocarriers leading to loss of siRNA and a diminished therapeutic outcome. Herein, we sought to explore how the nebulisation process, including adjustments in aerosol droplet size impacts the physicochemical properties of several lipid-based siRNA nanocarrier formulations. These included PEGylated and non-PEGylated cationic DOTAP-based lipoplexes (LPXs) and C12–200 based lipid nanoparticles (LNPs). Two Aerogen® Pro vibrating mesh nebuliser devices with capacities to generate aerosols of differing volumetric mean diameters (VMD) were utilised. The aerosol droplet sizes for the different siRNA formulations were 4.80 to 4.89 µm (High VMD device) and 3.56 to 3.59 µm (Low VMD device) demonstrating that the emitted droplet size distribution was consistent across multiple siRNA nanocarrier types. Further, the formulations exhibited mass median aerodynamic diameters (MMAD) of 4.03 – 4.84 µm (High VMD device) indicating their potential for targeting siRNA lung deposition. Aggregation in both lipoplex formulations and a significant reduction in LNPs’ siRNA encapsulation efficiency were observed. <em>In vitro</em> studies in Firefly luciferase (Fluc) expressing alveolar A549 cells demonstrated that cell viability and Fluc knockdown were generally unaffected by nebulisation. However, Fluc knockdown varied depending on formulation type and was highest for LNPs (93 %) and lowest for the PEGylated LPXs (max 30 %). Overall, this study shows that aerosols with consistent droplet size can be generated but the choice of nanocarrier impacts the stability and delivery efficacy and requires careful consideration for efficient nebulised siRNA delivery.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107386"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582080","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}