European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Intradermal delivery of teriflunomide loaded emulsomes using hollow microneedles for effective minimally invasive psoriasis management","authors":"Mariam Zewail ,&nbsp;Haidy Abbas ,&nbsp;Nesrine El Sayed ,&nbsp;Heba Abd-El-Azim","doi":"10.1016/j.ejpb.2025.114692","DOIUrl":"10.1016/j.ejpb.2025.114692","url":null,"abstract":"<div><div>Conventional topical psoriasis treatments suffer from limited delivery to affected areas along with skin irritation due to high local drug concentration. Herein an attempt to improve the delivery of leflunomide’s active metabolite (teriflunomide (TER)) by improving its solubility through nanoencapsulation in emulsomes (EMLs) besides ensuring effective intradermal delivery using hollow microneedles. Evaluation of colloidal characteristics of EMLs, encapsulation efficiency and drug release were performed. Additionally, the antipsoriatic activity in an imiquimod-induced psoriatic mouse model was evaluated by the measurement of inflammatory mediators’ levels and histopathological assessment of anatomized skin. The particle size of the chosen EMLs formulation was 147.9 nm and the zeta potential value was −21.7. Entrapment efficiency was 97.23 % and EMLs provided sustained drug release for 48 h. No statistically significant differences in the <em>in vivo</em> levels of NF-KB, IL 8, MMP1, GSH, SOD and catalase between the animals treated by TER-EMLs and the negative control cohort were observed. Also, histopathological inspection of dissected skin samples reflected the superiority of TER-EMLs over TER suspension. Collectively, combining nanoencapsulation and hollow microneedles application improved TER properties and ensured effective TER delivery to the affected psoriatic areas.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114692"},"PeriodicalIF":4.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Preparation of thrombin-loaded calcium alginate microspheres with dual-mode imaging and study on their embolic properties in vivo” [Eur. J. Pharm. Biopharm. 189 (2023) 98–108]","authors":"Tingting Han ,&nbsp;Luping Chen ,&nbsp;Fengyuan Gao ,&nbsp;Song Wang ,&nbsp;Jian Li ,&nbsp;Guangwen Fan ,&nbsp;Hailin Cong ,&nbsp;Bing Yu ,&nbsp;Youqing Shen","doi":"10.1016/j.ejpb.2025.114689","DOIUrl":"10.1016/j.ejpb.2025.114689","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114689"},"PeriodicalIF":4.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel long-acting phospholipid phase transition gel with progesterone effectively promoted uterine development","authors":"Bing Qin ,&nbsp;Mengling Yu ,&nbsp;Yong Qin ,&nbsp;Jianfeng Zuo ,&nbsp;Lianwen Qi","doi":"10.1016/j.ejpb.2025.114690","DOIUrl":"10.1016/j.ejpb.2025.114690","url":null,"abstract":"<div><div>Progesterone (PRG), a steroidal hormone, is commonly utilized in the clinical practice of obstetrics and gynecology. The high frequency of PRG injections, however, has brought significant pain and inconvenience to patients. In this study, we developed a long-acting injection leveraging the phase transition mechanism for the long-term treatment in Assisted Reproductive Technology (ART). The components we selected all possess excellent biocompatibility. Pharmacokinetic studies revealed that the PRG-loaded phospholipid phase transition gels (PRG-PPTGs) released the PRG continuously for over 7 days. Notably, pharmacological investigation demonstrated that PRG-PPTGs, when administered weekly, effectively promoted uterine development. Our findings suggested that PRG-PPTGs successfully achieve both the prevention of burst release and the reduction of dosing frequency, highlighting the potential of PPTGs as promising long-acting composite system for hydrophobic drugs.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114690"},"PeriodicalIF":4.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide-based hydrogel co-assembled with antibody-drug for enhanced retinal cell uptake and attenuated experimental autoimmune uveitis","authors":"Mali Dai ,&nbsp;Pengyuan Du ,&nbsp;Yijing Li ,&nbsp;Xiaiting Wang ,&nbsp;Jinrun Chen ,&nbsp;Hui Liu ,&nbsp;Wenqiao Zhang ,&nbsp;Jianhong Zhou ,&nbsp;Xingyi Li ,&nbsp;Yuqin Wang","doi":"10.1016/j.ejpb.2025.114691","DOIUrl":"10.1016/j.ejpb.2025.114691","url":null,"abstract":"<div><div>Effective treatment of chronic posterior ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration requires improvements in targeted drug delivery strategies. This study introduces a novel injectable drug delivery system co-assembled with a peptide-based hydrogel and secukinumab (SEK), an IL-17A neutralising monoclonal antibody, targeting retinal pigmented epithelium (RPE) cells. Compared to a SEK solution, the SEK loaded hydrogel significantly enhanced the protein uptake (3.7 times higher) by RPE cells in an inflammatory state after 24 hours of treatment and increased the drug concentration in retinal tissues during 20 days of treatment. A single intravitreal injection of the SEK loaded hydrogel effectively suppressed inflammation in a uveitis model. It also reduced the immunoreactivity of microglia and T helper 17 cells, preserved the integrity of the blood-retina barrier, mitigated retinal cell apoptosis, and facilitated the recovery of the retinal function. This delivery system comprising an antibody-drug co-assembled with a peptide-based hydrogel shows promising potential for targeting the retina and treating complex chronic posterior ocular diseases.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114691"},"PeriodicalIF":4.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication and characterization of dissolving microneedles combining digital light processing and vacuum compression molding technique for the transdermal delivery of rivastigmine","authors":"Paraskevi Kyriaki Monou ,&nbsp;Eirini Saropoulou ,&nbsp;Laura Andrade Junqueira ,&nbsp;Siva Satyanarayana Kolipaka ,&nbsp;Eleftherios G. Andriotis ,&nbsp;Emmanouil Tzimtzimis ,&nbsp;Dimitrios Tzetzis ,&nbsp;Chrysanthi Bekiari ,&nbsp;Nikolaos Bouropoulos ,&nbsp;Bethany Harding ,&nbsp;Orestis L. Katsamenis ,&nbsp;Andreas Bramböck ,&nbsp;Daniel Treffer ,&nbsp;Dennis Douroumis ,&nbsp;Dimitrios G. Fatouros","doi":"10.1016/j.ejpb.2025.114687","DOIUrl":"10.1016/j.ejpb.2025.114687","url":null,"abstract":"<div><div>Dissolving microneedles (MNs) are promising transdermal drug delivery systems that can effectively increase the absorption of the drugs. They bypass the first layer of the skin, the stratum corneum (SC) and deliver the drugs directly into the dermis, by dissolving inside the interstitial fluid and releasing the active. The traditional ways of MN fabrication involve primarily micromolding, which basically uses silicone molds. Drugs and polymer mixture solutions are poured into these molds and after drying the MN arrays are carefully removed. In the present study, a novel molding process was employed to fabricate dissolving MNs containing rivastigmine (RIV). RIV is available as an oral tablet and a transdermal patch. The patch (Exelon®), used for managing Alzheimer’s symptoms in mild to moderate dementia, releases only about 50 % of its drug content, raising concerns about dose wastage, environmental impact, and patient costs. Thus, RIV was selected as the model drug to fabricate MNs by combining to novel processes, Digital Light Processing and Free-D Molding, a Vacuum Compression Molding (VCM) Technique provided by MeltPrep®. The developed arrays were evaluated regarding their physiochemical characteristics and their ability to penetrate the skin without breaking or creating fragments, as they can withstand forces up to 600 N. The MNs were visualized using optical microscopy, SEM, and CLSM to examine their geometry, surface and length (0.708 mm). Permeability studies verified that the MNs can increase significantly RIV transportation across the skin, up to 9-fold. Histological analysis was conducted to ensure that the produced MNs are safe for transdermal applications. Overall, the present study suggests that Free-D molding, a combination of 3D printing and VCM can produce dissolving MN arrays that are effective and safe for transdermal applications.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114687"},"PeriodicalIF":4.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Studying the effects of polymers on therapeutic deep eutectic solvents’ formation and stability: A thermal analysis-based approach to optimise polymer selection","authors":"Magdy M. Abdelquader ,&nbsp;Shu Li ,&nbsp;Gavin P. Andrews ,&nbsp;David S. Jones","doi":"10.1016/j.ejpb.2025.114685","DOIUrl":"10.1016/j.ejpb.2025.114685","url":null,"abstract":"<div><div>Therapeutic deep eutectic solvents (THEDES) are the liquids produced upon mixing two solid materials, where at least one of them is an active pharmaceutical ingredient. The strong hydrogen bonding (HB) between the parent materials is the reason for such profound depression in their melting points. THEDES formation can improve drugs’ solubility and permeation characteristics. However, this can be limited by their encapsulation within drug delivery platforms e.g., polymeric matrices which might disrupt the HB network of THEDES by introducing new HB active sites into the mixture. Despite this, the effects of polymers on THEDES stability are not well-documented. In addition, the polymers’ impact on THEDES formation during end-to-end production has not been studied.</div><div>In this work, these issues were addressed by employing thermal processing of polymers and drugs. The dually active lidocaine: flurbiprofen (1:1) THEDES was utilized in addition to model polymers, namely polyethylene-co-vinyl acetate (PEVA), polyethylene oxide (PEO) and Eudragit® RL PO (EuRLPO). Firstly, probing the interaction between the polymers and the individual components of THEDES revealed that PEVA has no affinity towards both drugs while PEO can interact with flurbiprofen, and EuRLPO can interact with lidocaine. Then, to study the effect of the polymers on THEDES formation and stability, a valid in-situ method was developed to quantify THEDES in its mixture using modulated temperature differential scanning calorimetry (MTDSC). MTDSC data showed that the three polymers retarded THEDES formation in the following order PEVA &lt; EuRLPO &lt; PEO. This retardation was attributed to increased medium viscosity and the subsequent reduction in THEDES formation rate. Increasing the heating time led to complete THEDES formation in the case of PEVA and EuRLPO but not with PEO. This result was explained based on the polymers’ interaction with THEDES parent drugs and inputs from polymers’ viscoelastic properties. On the other hand, introducing the polymer after THEDES formation mitigated their viscosity effect but their interaction with the parent drugs remained an issue, where PEO and EuRLPO were able to destabilize the pre-formed THEDES to variable extents. Long-term storage stability study further confirmed this conclusion.</div><div>Therefore, this study will provide valuable information regarding the interaction (or lack of) of THEDES with model pharmaceutical polymers that have been thermally processed and will provide recommendations regarding the rational choice of polymers to maintain THEDES stability.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114685"},"PeriodicalIF":4.4,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking the virus: Yeast glucans as an effective alternative to acyclovir in HSVI treatment","authors":"Diana Tavares-Valente ,&nbsp;Helena Moreira ,&nbsp;Pedro Sousa ,&nbsp;Manuela Amorim ,&nbsp;António Conde ,&nbsp;Manuela Pintado ,&nbsp;João Fernandes ,&nbsp;João Azevedo-Silva","doi":"10.1016/j.ejpb.2025.114684","DOIUrl":"10.1016/j.ejpb.2025.114684","url":null,"abstract":"<div><div>Glucans, structural polysaccharides in the yeast cell wall, are known for their biological and immunomodulatory capacities, helping in prevention and management of infections. Herpes simplex virus type 1 (HSVI) is a prevalent infection that causes great comorbidity and is challenging to treat due to the adverse effects of standard antiviral drugs like acyclovir. This study assessed the potential of yeast glucans extracted from two different origins − a steviol-glycoside producing strain and a wild-type strain- to circumvent HSVI infection, either <em>in vitro</em> and <em>ex vivo</em>. Treatment with glucans in keratinocytes and macrophages <em>in vitro</em> reduced cell infection similarly to acyclovir. However, unlike acyclovir, glucans demonstrated an immunostimulatory effect, increasing the production of IL-1β, TNF-α and IL-6. Additionally, both glucans were formulated with squalane for skin application. This formulation improved glucans penetration in the skin, restored skin structure and reduced the cytopathic effect of HSVI infection. In summary, this study highlights yeast glucans as a natural therapeutic alternative for HSVI treatment, offering an option with an excellent safety profile. Moreover, using glucans from industrial side-streams promotes a sustainable approach, contributing to the circular economy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114684"},"PeriodicalIF":4.4,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel development of Poly(2-ethyl-2-oxazoline)-based mucoadhesive buccal film for poorly water-soluble drug delivery via hot-melt extrusion","authors":"Ziru Zhang ,&nbsp;Sheng Feng ,&nbsp;Rasha El-Kanayati ,&nbsp;Indrajeet Karnik ,&nbsp;Sateesh Kumar Vemula ,&nbsp;Michael A. Repka","doi":"10.1016/j.ejpb.2025.114686","DOIUrl":"10.1016/j.ejpb.2025.114686","url":null,"abstract":"<div><div>The first-pass effect and low water solubility are crucial limitations that hinder the drug from being absorbed into the systemic circulation, followed by oral administration. The mucoadhesive buccal delivery system offers direct drug absorption through the mucosa, reaching systemic circulation and bypassing the hepatic first-pass metabolism. This approach ensures high bioavailability and overcomes the swallowing difficulties associated with traditional oral delivery systems. Here, we developed mucoadhesive buccal films for oral delivery of poorly water-soluble drugs using hot-melt extrusion (HME). Poly(2-ethyl-2-oxazoline) (PEtOx), a potential pharmaceutical excipient with high biocompatibility and versatility, was used as the primary matrix for solubility enhancement. Fenofibrate (FB), a typical Biopharmaceutics Classification System (BCS) class II drug with virtually insolubility in water, was used as the model drug. Hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and polyethylene oxide (PEO) were combined with PEtOx to adjust the mucoadhesive property. The prepared films were <em>in vitro</em> characterized to delineate the impact of key formulation factors on the mechanical properties, bioadhesion, and solubility enhancement effect. We demonstrated that the complexation of PEtOx with 20% PEO (F8) resulted in over 95% drug release within 2 h, representing an over 5-fold enhancement in solubility compared to the free drug. This F8 formulation exhibited significant bioadhesion among the other formulations, with a 2.2- to 2.7-fold increase in Peak Force (PAF) and work of adhesion (WAD) relative to the control group. This study investigates HME as a continuous fabrication process for developing PEtOx-based buccal film, demonstrating a potential bioadhesive drug delivery system with a solubility improvement effect.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114686"},"PeriodicalIF":4.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA pharmaceutics: Formulation technology, biophysics and kinetics","authors":"Ulrich Lächelt (Guest Editor)","doi":"10.1016/j.ejpb.2025.114683","DOIUrl":"10.1016/j.ejpb.2025.114683","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114683"},"PeriodicalIF":4.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrophobic interactions enhance doxorubicin delivery from hyaluronic acid nanogels","authors":"Yu-Chu Su ,&nbsp;Yi-Cheng Chen ,&nbsp;Yi-Hsuan Lo ,&nbsp;Chien-Hsiang Chang ,&nbsp;Yu-Fon Chen","doi":"10.1016/j.ejpb.2025.114676","DOIUrl":"10.1016/j.ejpb.2025.114676","url":null,"abstract":"<div><div>This study introduces a novel targeted chemotherapy approach employing biocompatible nanogels engineered from hyaluronic acid (HA) and pitaya-derived DNA. Both polymers were functionalized with aldehyde groups, enabling crosslinking and subsequent encapsulation of doxorubicin (DOX). The incorporation of DNA significantly enhanced DOX loading, achieving a remarkable encapsulation efficiency of 93.3%. Notably, the integration of a hydrophobic 4,4′-dithiodianiline (DTD) linker facilitated controlled drug release within the reductive tumor microenvironment, with 36% of DOX released within 24 h in response to glutathione (GSH). These nanogels demonstrated targeted delivery to CD44-overexpressing cancer organoids, exhibiting a 6.7- to 15-fold increase in cellular uptake compared to free DOX. This enhanced intracellular DOX delivery significantly increased apoptosis in both cancer cells and organoids, as evidenced by increased condensed DNA and a 1.86- to 6.9-fold increase in poly ADP-ribose polymerase (PARP) expression. Importantly, hydrophobic interactions between the DTD linker and the cell membrane were found to significantly contribute to the efficient cellular uptake of the nanogels, resulting in a 2.6- to 9.1-fold reduction in IC₅₀ values compared to free DOX. These findings highlight the potential of HA-based nanogels with cleavable linkers as promising platforms for targeted drug delivery and enhanced cancer therapy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114676"},"PeriodicalIF":4.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}