European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Glow in the dark tumor: Enhanced near-IR visualization and destruction of cancer with a self-quenched theranostic.","authors":"S İrem Güler, Cem Levent Altan, E Esma Demircioglu, Nihan Verimli, Beyza Abisoglu, Cigdem Bayraktaroglu, Mustafa Caglar Beker, S Sibel Erdem","doi":"10.1016/j.ejpb.2025.114632","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114632","url":null,"abstract":"<p><p>Late diagnosis is one of the major obstacles for the treatment of breast cancer which can be overcome with a system offering sensitive imaging and selective therapeutic effect. In this study, we developed a \"dark-bright\" multifunctional drug delivery system bringing real-time imaging and non-invasive therapy together. Theranostic ability of the system was delivered by Verteporfin (VP), serving as a fluorescence probe and a photosensitizer. To create a \"dark state\" system via self-quenching ability of VP, it was immobilized onto the superparamagnetic iron oxide nanoparticle (SPION) surface. Upon cellular uptake of the \"dark state\" system, release of VP led to fluorescence regain, switching the system to \"bright state\" after which photodynamic therapy (PDT) was initiated to lead to cell death. Theranostic feature of the system was evaluated in MCF-7 and MDA-MB-231 cell lines. Following internalization, fluorescence signal was increased up to ∼56-fold in MCF-7 cells. The IC₅₀ value decreased ∼20-fold and ∼117-fold in MCF-7 and MDA-MB-231 cell lines, respectively. Moreover, the system significantly inhibited migration in the highly aggressive MDA-MB-231 cell line and induced apoptosis by caspase-3 activation. The developed \"dark-bright\" system is a promising multifunctional drug delivery vehicle with extraordinary theranostic features for the detection and destruction of micro tumors.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114632"},"PeriodicalIF":4.4,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002680","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":"Excipients in drug delivery systems: A comprehensive review of approved inactive ingredients for human ophthalmic formulations.","authors":"Raquel Arribada, Daniela Rodrigues-Braz, Armando Silva-Cunha, Francine Behar-Cohen","doi":"10.1016/j.ejpb.2025.114637","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114637","url":null,"abstract":"<p><p>Pharmaceutical excipients, commonly known as inactive ingredients, encompass any substance aside from the active ingredient that fulfills a distinct and vital role in a formulation. Their purpose is to enhance specific characteristics, whether associated with the performance of the formulation or aspects related to patient comfort, safety, and acceptability. Because of the limited toxicity studies provided, and the several allergic and toxic side effects that have been reported throughout the years, it is not trivial for the regulatory agencies to approve inactive ingredients for human use. In general, excipients are approved within good manufacturing practices (GMPs) when they undergo analysis of the formulation as a whole, not the standalone substance. However, there is a lack of updated information regarding this subject, given that only the American Food and Drug Administration (FDA) provides a complete list describing the inactive ingredients that are currently approved in drug products for human use. Here, we aimed to provide an overview of key excipients approved by the FDA for ophthalmic use in humans, focusing on their functional roles in ophthalmic formulations, particularly eye drops, and the regulatory requirements involved in these ingredients approval.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114637"},"PeriodicalIF":4.4,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002655","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":"Advances in soft nanoparticle-based platforms for human and veterinary trichomoniasis therapy: A scoping review.","authors":"Raul Edison Luna Lazo, Fernando Miguel Stelmach Alves, Eric Luiz Domingos, Alexandre de Fatima Cobre, Paulo Vitor Farago, Letícia Cruz, Tiana Tasca, Roberto Pontarolo, Luana Mota Ferreira","doi":"10.1016/j.ejpb.2025.114638","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114638","url":null,"abstract":"<p><p>This scoping review focuses on drug delivery systems based on soft materials designed for the administration of drugs with anti-Trichomonas vaginalis activity. It primarily examines their use in addressing human trichomoniasis, exploring their physicochemical characteristics, in vitro and in vivo evaluation and identifying existing challenges and gaps. Given the economic burden and the One Health approach, formulations developed aiming at treating animal infections - cattle and poultry - were also discussed. The review involved searching electronic databases, such as PubMed, Scopus, and Web of Science, to find studies published until May 2024; out of the 103 articles retrieved, 18 fulfilled the eligibility criteria. This study investigated soft-nanoparticle formulations, including polymericand lipid-based systems, and their incorporation into suitable formulations for topical application, including hydrogels and polymeric films. Additionally, the discussion covered toxicology and highlighted the knowledge gaps related to the potential use of these formulations in humans. Anti-trichomonas soft nano-based formulations emerge as promising candidates for treating gynecological and animal infections. In conclusion, further preclinical testing is necessary, as none of the formulations have progressed to human clinical trials and have only been evaluated in animal models.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114638"},"PeriodicalIF":4.4,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002645","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":"Control of biomedical nanoparticle distribution and drug release in vivo by complex particle design strategies.","authors":"Melanie Bresinskya, Achim Goepfericha","doi":"10.1016/j.ejpb.2025.114634","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114634","url":null,"abstract":"<p><p>The utilization of targeted nanoparticles as a selective drug delivery system is a powerful tool to increase the amount of active substance reaching the target site. This can increase therapeutic efficacy while reducing adverse drug effects. However, nanoparticles face several challenges: upon injection, the immediate adhesion of plasma proteins may mask targeting ligands, thereby diminishing the target cell selectivity. In addition, opsonization can lead to premature clearance and the widespread presence of receptors or enzymes limits the accuracy of target cell recognition. Nanoparticles may also suffer from endosomal entrapment, and controlled drug release can be hindered by premature burst release or insufficient particle retention at the target site. Various strategies have been developed to address these adverse events, such as the implementation of switchable particle properties, regulating the composition of the formed protein corona, or using click-chemistry based targeting approaches. This has resulted in increasingly complex particle designs, raising the question of whether this development actually improves the therapeutic efficacy in vivo. This review provides an overview of the challenges in targeted drug delivery and explores potential solutions described in the literature. Subsequently, appropriate strategies for the development of nanoparticular drug delivery concepts are discussed.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114634"},"PeriodicalIF":4.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002646","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":"Robust near-infrared modeling for pharmaceutical powder streams: External variable augmented iterative optimization technology (EVA-IOT).","authors":"Natasha L Velez-Silva, Adam J Rish, James K Drennen, Carl A Anderson","doi":"10.1016/j.ejpb.2025.114626","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114626","url":null,"abstract":"<p><p>The adoption of pure component models, such as iterative optimization technology (IOT) algorithms, is gaining significant interest in the pharmaceutical industry, primarily because of their calibration-free/minimal calibration requirements for process analytical technology applications. The IOT methods have recently demonstrated great potential for monitoring the quality of continuous powder mixtures by Near-infrared (NIR) spectroscopy. However, the dynamic conditions of continuous manufacturing processes may limit the effectiveness of such approaches. Density variations introduced to NIR spectra that are collected from dynamic powder mixtures at different process conditions is detrimental to the drug prediction accuracy and robustness of IOT methods. This work introduces a new method, called external variable augmented iterative optimization technology (EVA-IOT), which incorporates the shape of non-chemical external sources of variability into the pure component spectra matrix to improve the prediction accuracy and robustness of the base IOT algorithm. This approach derives the shape of non-chemical external variables from the latent structure of decomposition methods using NIR spectra acquired from a single mixture at known levels of the external variable. A density-augmented EVA-IOT method was developed and implemented to quantify the active pharmaceutical ingredient (API) in continuous powder mixtures flowing at varying process conditions in a simulated continuous process. The EVA-IOT method demonstrated a significantly enhanced API prediction accuracy and robustness against process variation compared to alternative IOT methods. The overall prediction performance of EVA-IOT was comparable to that of global partial least square (PLS) regression models while reducing the calibration burden up to 97%. This makes EVA-IOT a material-sparing alternative to calibration-intensive robust decomposition modeling approaches for monitoring the quality of continuous pharmaceutical powder streams.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114626"},"PeriodicalIF":4.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002751","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":"Thumb-sized 3D-Printed cymbal microneedle array (CyMA) for enhanced transdermal drug delivery.","authors":"Ziyan Chen, Kai Ye, Huayi Wu, Lanyuan Peng, Zeyu Chen","doi":"10.1016/j.ejpb.2025.114629","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114629","url":null,"abstract":"<p><p>Transdermal drug delivery presents a compelling alternative to both needle injection and oral ingestion of medication, as it enhances patient adherence and convenience through its non-invasive and painless administration method. The use of microneedles penetrates the barrier of the stratum corneum, facilitating the sustained delivery of drugs across the skin. However, their efficacy has been limited by the slow diffusion of molecules and often requires external triggers. Herein, a lightweight and minimized 3D-printed microneedle array is introduced, employing a cymbal-type ultrasound transducer, as the external engine for deeper and faster transdermal drug delivery. A theoretical finite element model was developed and the optimization design was conducted for structural parameters. The optimized assembled prototype was fabricated using high-precision 3D printing and weighs only 20 g. In vivo experiments using a diabetic mouse model demonstrate that local insulin delivery with CyMA achieves systemic effects comparable to intraperitoneal administration. Such compact and effective microneedle delivery technology offers considerable promise therapeutic applications on the skin and intraoral use.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114629"},"PeriodicalIF":4.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002754","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":"A novel levodopa-carbidopa three-layer gastroretentive tablet for improving levodopa pharmacokinetics.","authors":"Xiangcheng Zhao, Peng Yan, Hailong Zhang, Wenhu Zhou, Jinsong Ding","doi":"10.1016/j.ejpb.2025.114633","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114633","url":null,"abstract":"<p><p>The narrow absorption window of levodopa and the significant impact of peripheral decarboxylase are the most limiting factors in maintaining prolonged and smooth plasma concentration in patients with Parkinson's disease (PD). Therefore, this study aims to design a novel gastroretentive carbidopa-levodopa three-layer tablet, which consists of an expansion layer, an immediate-release layer, and a sustained-release layer. The expansion layer rapidly expanded with sufficient structural strength and stayed in the beagle's stomach for more than 10 h, delineating excellent gastric retention effects. The immediate-release layer quickly released the drug and the sustained-release layer maintained a stable drug concentration. Importantly, pharmacokinetic data obtained under fed conditions demonstrated that the duration of efficacy of the three-layer tablets was significantly superior to that of the commercially available product Sinemet® CR, with effective levodopa blood levels remaining for up to 12 h. This is expected to offer more convenient clinical medication options for patients with PD.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114633"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002565","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":"Patches containing quercetin microcapsules to ameliorate dermal herpes simplex virus injuries in mice.","authors":"Jéssica Bassetto Carra, Maria Laura Goussain Darido, Camila Felix Vecchi, Mariana Carla de Oliveira, Ricardo Luís Nascimento de Matos, Pietra Mitiko Tateyama Pattini, Bianca Larissa Masquetti, Beatriz da Silva Tavares, Marcos Luciano Bruschi, Ana Paula Frederico Rodrigues Loureiro Bracarense, Renê Oliveira do Couto, Rubia Casagrande, Sandra Regina Georgetti, Waldiceu A Verri, Ligia Carla Faccin Faccin-Galhardi, Marcela Maria Baracat","doi":"10.1016/j.ejpb.2025.114631","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114631","url":null,"abstract":"<p><p>This study aimed to develop patches containing quercetin-loaded microcapsules and to evaluate their in vitro and in vivo safety and efficacy in preclinical surveys. A set of in vitro experiments evidenced the virucidal activity of quercetin against the HSV-1-KOS (sensitive to acyclovir) and HSV-1-AR (resistant to acyclovir) strains, with improved outcomes upon the first. The patches presented a homogeneous aspect, were easily handled, had a suitable bioadhesion, and possessed mechanical properties of soft and weak material, besides a pH compatible with human skin. The in vitro release profile of quercetin showed an initial burst release, followed by a controlled release rate, which was best described by Gompertz kinetics (R² of 0.93). Using quercetin-loaded patches for treating HSV-1-KOS-induced injuries was feasible since they were well tolerated in the in vivo skin irritation test and significantly decreased the injury scores until the fourth out of eight days of treatment in mice compared to acyclovir cream (50 mg/g). Altogether, the in vitro and in vivo antiviral assays indicate that this flavonol acts in the earlier stage of the infection, likely impairing the HSV-1 adsorption to the cell. The anti-inflammatory capacity of the quercetin-loaded patches was noteworthy as evidenced by histological analysis. These findings bring prospects for safer and more effective management of mucocutaneous HSV-1 injuries.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114631"},"PeriodicalIF":4.4,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982938","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":"Bupivacaine multivesicular liposomes/meloxicam nanocrystals in a thermosensitive gel adapted to the \"microenvironment\" for long-term analgesia.","authors":"Dongxu Gao, Yuan Zhao, Junfeng Liu, Runxuan Chu, Junji Wang, Wei Bian, Xuejie Liu, Weigen Lu, Jun He","doi":"10.1016/j.ejpb.2025.114630","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114630","url":null,"abstract":"<p><p>Current analgesics on the market exhibit a short duration of action and induce the production of inflammatory factors in tissues damaged by surgical procedures. Inflammatory factor production can create acidic environments, limiting drug delivery. In this study, we developed a novel injectable formulation comprising bupivacaine multivesicular liposomes of high osmotic pressure (H-MVL) and meloxicam nanocrystals (MLX) in a thermosensitive gel (H-MVL/MLX@GEL) adapted to the microenvironment for long-term postoperative analgesia. To achieve formulation stability, H-MVL were prepared by regulating the osmotic pressure of the gel system. Moreover, the inclusion of MLX serves to not only attenuate local inflammatory factors, regulating the acidic microenvironment, but also to prolong the duration of action of meloxicam (MEL). The increased absorption of bupivacaine (BUP) and the prolongation of the half-life of BUP release in H-MVL/MLX@GEL were demonstrated through pharmacokinetic experiments. Sciatic nerve block models and hot plate analgesia tests demonstrated that H-MVL/MLX@GEL effectively alleviated pain for at least five days. The immunohistochemical results showed that the addition of MLX reduced the production of the local inflammatory factors interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), thereby improving the analgesic effect by regulating the local acidic environment and alleviating local irritation.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114630"},"PeriodicalIF":4.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970236","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":"Alteration of gel point of poloxamer 338 induced by pharmaceutical actives and excipients.","authors":"Natalie Deiringer, Fabian Fischer, Martin Hofsäss, Meik Ranft, Sophia Ebert","doi":"10.1016/j.ejpb.2025.114628","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114628","url":null,"abstract":"<p><p>Poloxamer 338 is used as versatile thermo-responsive gelling agent in topical and sub-cutaneous applications. Due to application specific needs a gel point below body or even below room temperature is required. The influence of inorganic salts and active pharmaceutical ingredients (APIs) on the gel point was investigated using oscillatory rheology to identify the driving forces and predictors for gel point alteration. While most inorganic salts decreased the gel point, API salts exhibited an increase. Consistent with previous findings, the extent of gel point alteration caused by inorganic salts could be empirically described by the Hofmeister series, primarily influenced by the anion. Notably, this study revealed a concentration-dependent increase in the gel point in the presence of API salts. Moreover, this increase could be accurately predicted in a linear manner by considering the respective logP value. By utilizing the proposed prediction model, the effect of API addition on the gel point can be estimated, facilitating formulation development to achieve the desired gelling behavior for specific applications.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114628"},"PeriodicalIF":4.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970234","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}