European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Dual targeted lipid nanoparticles for enhanced DNA delivery and transfection of breast cancer cells","authors":"Claudia Lotter ,&nbsp;Megan Anna Stierli ,&nbsp;Ramya Deepthi Puligilla,&nbsp;Jörg Huwyler","doi":"10.1016/j.ejpb.2025.114674","DOIUrl":"10.1016/j.ejpb.2025.114674","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) have gained much attention as non-viral gene delivery systems due to their large payload capacity, reduced immunogenicity, and cost-effective manufacturing. Surface modification of LNPs by covalent attachment of receptor ligands can improve their tissue specificity and reduce off-target effects. In the present work, DNA-LNPs were therefore designed to target breast cancer, particularly the invasive HER2-positive subtype. Targeting was mediated by trastuzumab (Herceptin®) a monoclonal antibody binding to the extracellular domain of the human epidermal growth factor receptor protein (HER2). To overcome intrinsic trastuzumab resistance for some patients with HER2 positive breast cancer, a dual-targeting strategy was employed by combining Herceptin with folate to enhance LNP uptake by cancer cells.</div><div>Dual-targeted LNPs encapsulating plasmid DNA, coding for a fluorescent reporter protein (tdTomato or EGFP), were prepared using folate-conjugated PEGylated lipids. Subsequently, thiolated Herceptin was conjugated to the surface of the LNPs. At an N/P ratio of 6, small and uniform targeted LNPs were obtained, with a slightly negative ζ-potential. Cellular uptake and transgene expression were characterized <em>in<!--> <!-->vitro</em> using three breast cancer cell lines (MCF7, MDA-mb453, SKBR3), which express varying level of the HER2 receptor. Cellular uptake correlated with HER2 expression levels and was significantly increased when Herceptin was combined with folate. In all tested breast cancer cell lines, dual-targeted LNPs led to an enhanced transgene expression compared to single-targeted LNPs. Furthermore, <em>in<!--> <!-->vivo</em> zebrafish xenograft studies confirmed superior targeting and transfection efficiency of Dual-LNPs under physiological conditions.</div><div>Our findings highlight the superior performance of dual-targeted LNPs to deliver a DNA expression plasmid to HER2 positive breast cancer cells, emphasizing their potential as an improved targeting and transfection strategy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"209 ","pages":"Article 114674"},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471719","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":"Raloxifene HCl – Naringin co-amorphous system: Preparation, characterization and pharmacokinetic studies","authors":"Navya Sree Kola Srinivas ,&nbsp;Dani Lakshman Yarlagadda ,&nbsp;Brahmam Bheemishetty ,&nbsp;Shaila Lewis ,&nbsp;Swapnil Jayant Dengale ,&nbsp;Krishnamurthy Bhat","doi":"10.1016/j.ejpb.2025.114667","DOIUrl":"10.1016/j.ejpb.2025.114667","url":null,"abstract":"<div><div>Approximately 90 % of NCEs in development and 40 % of recently approved drugs are poorly water-soluble. To improve solubility and stability, co-amorphous systems (CAMs) are used, involving the amorphization of an API with a co-former through interactions like hydrogen bonding. This study explores the co-amorphization of Raloxifene HCl (RLX) and Naringin (NRG). RLX, a BCS class II drug, has limited oral bioavailability of only 2 % due to its poor solubility (0.5 μg/mL) and extensive pre-systemic metabolism. Additionally, it interacts with CYP3A4 and P-glycoprotein (P-gp). NRG, a compound found in citrus fruits, inhibits both CYP3A4 and P-gp. Therefore, utilizing NRG to prepare RLX CAMs could result in a compound with improved solubility and enhanced bioavailability. CAMs were prepared using the solvent evaporation technique, followed by solid-state characterization at the molecular level. Solubility, drug release, and both ex vivo and in vitro studies were conducted. CAMs showed a 3.5-fold solubility increase and a 10-fold increase in ex-vivo permeation compared to RLX. In vivo studies showed an 8.1-fold improvement in Cmax and a 2.8-fold increase in AUC, indicating significantly enhanced bioavailability. These results suggest that co-amorphization could be a viable platform technology for improving API properties at the molecular level.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"209 ","pages":"Article 114667"},"PeriodicalIF":4.4,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436709","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":"Investigation of powder properties and application aspects impacting nasal deposition of spray-dried powders in a nasal cast","authors":"Angelika Jüptner ,&nbsp;Regina Scherließ","doi":"10.1016/j.ejpb.2025.114666","DOIUrl":"10.1016/j.ejpb.2025.114666","url":null,"abstract":"<div><div>In this study, spray-dried formulations differing in morphology (spherical and wrinkled), surface polarity (hydrophilic and hydrophobic), and size (20–30 µm and 3 <!--> <!-->µm) were evaluated in a nasal cast to assess their deposition profiles. The objective was to identify how formulation properties and application aspects influence the deposition profile. For this purpose, the formulations were administered at different application angles (45° and 60°), fill weights (20 <!--> <!-->mg and 40 <!--> <!-->mg), and airflow rates (0 <!--> <!-->L/min and 15 <!--> <!-->L/min) in conjunction with a UDS powder device. The results indicate a more posterior deposition profile for 45° compared to 60° due to increased deposition in the turbinate region; conversely, deposition profiles between fill weights were comparable. Application with simultaneous airflow should be avoided because of an increasing postnasal fraction. No influence of morphology could be observed, but for the surface polarity an influence was apparent, if the powder was applied with a simulated inspiration. In these cases, a hydrophobic formulation was better dispersible than a hydrophilic formulation, which led to an increased postnasal fraction. A particle size for pulmonary application demonstrated comparable results to nasal formulations with respect to the turbinate deposition but exhibited a high postnasal fraction for hydrophobic formulations.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"209 ","pages":"Article 114666"},"PeriodicalIF":4.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425291","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":"Mannose-6-phosphate-PEG-lipid conjugates improve liposomal uptake","authors":"Boris Sevarika ,&nbsp;Deniz Capri ,&nbsp;Joël Frey ,&nbsp;Margarita C. Dinamarca ,&nbsp;Daniel Häussinger ,&nbsp;Scott McNeil","doi":"10.1016/j.ejpb.2025.114665","DOIUrl":"10.1016/j.ejpb.2025.114665","url":null,"abstract":"<div><div>Targeted liposomes are a keystone of nanomedicine, offering a precise and efficient means to deliver therapeutic agents directly to diseased tissues or cells. By incorporating targeting ligands on their surface, liposomes enhance the specificity of drug delivery, improving efficacy and reducing toxicity. Mannose-6-phosphate (M6P) is a crucial molecular tag for internalization and intracellular sorting of macromolecular structures to the lysosome. Taking advantage of this mechanism, we designed and developed liposomal systems to enhance therapeutic delivery to the lysosomes. The synthesized M6P-based targeting molecules were covalently coupled to a phospholipid using a polyethylene glycol (PEG) linker. The prepared ligands were successfully incorporated into the liposomes, yielding a size of roughly 100 nm and a zeta potential of around −40 mV. Incorporating the M6P-based ligand enhances the internalization of liposomes in a concentration-dependent manner, increasing uptake by up to 14-fold in several tested cell lines. In contrast, structurally similar monosaccharides and equally charged ligands failed to replicate this effect, highlighting the specificity of M6P-mediated internalization. Our studies demonstrate that M6P-mediated uptake predominantly occurs via a clathrin-mediated pathway, and once internalized, 72 % of the M6P-coated liposomes are associated with the lysosomal compartment. This study highlights the potential of M6P-based liposomal carriers as a modular platform for targeted lysosomal delivery, offering a promising therapeutic approach for lysosomal storage diseases.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"209 ","pages":"Article 114665"},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425294","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":"Thymol@pro-phytomicelles as an antibiotic alternative in livestock and poultry farming: preparation, characterization, and in vitro and in vivo antimicrobial activity evaluation","authors":"Linrong Yu ,&nbsp;Yunchun Pan ,&nbsp;Qingqian Meng ,&nbsp;Xianggen Wu ,&nbsp;Mengshuang Li","doi":"10.1016/j.ejpb.2025.114664","DOIUrl":"10.1016/j.ejpb.2025.114664","url":null,"abstract":"<div><div>Antibiotic abuse in livestock and poultry farming poses significant threats to human health, including the emergence of drug-resistant bacteria. Thus, antibiotic alternatives are highly required in this field. Thymol (THY) demonstrates significant potential as an antibiotic alternative, but its commercial application is limited due to its high volatility and low water solubility. In this study, a novel nanoformulation of pro-phytomicelles, with glycyrrhizin and rebaudioside A as mixed-nanocarriers that load THY (called “THY@pro-phytomicelles”), was designed and tested as a potent antibiotic alternative. The optimized THY@pro-phytomicelles had an encapsulation efficiency of 99.75 ± 0.37 % and a particle size of 3.83 ± 0.44 nm after they were dispersed in water. Following THY’s formulation into THY@pro-phytomicelles, its water solubility, volatility stability, and antioxidant activity significantly improved. In vitro, the THY@pro-phytomicelles showed better antimicrobial activity than THY. Their antibacterial mechanism appeared to involve destruction of the integrity of the bacterial cell wall and biomembrane, leading to alkaline phosphatase (AKP) leakage and inhibition of biofilm formation. In the animal evaluation in this study, they showed excellent in vivo antibacterial capacities against <em>Salmonella enteritidis</em>-induced enteritis, including improvement of the liver bacterial abscess, alleviation of the oxidative stress and inflammatory cytokine levels, reduction of the bacterial load of the liver, and alleviation of the inflammation and damage caused by bacteria in the cecum. Overall, the THY@pro-phytomicelles showed excellent in vitro and in vivo antibacterial activity, making them a potentially effective antibiotic alternative in livestock and poultry farming, with broad potential application in the breeding industry.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114664"},"PeriodicalIF":4.4,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387007","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":"The revival of the mini-tablets: Recent advancements, classifications and expectations for the future.","authors":"Valentinë Lura, Ard Lura, Jörg Breitkreutz, Viviane Klingmann","doi":"10.1016/j.ejpb.2025.114655","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114655","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Mini-tablets have recently raised huge interest in pharmaceutical industry. The present review aims to identify the rational, the opportunities and challenges of this emerging small solid drug dosage form by a structured literature review following the PRISMA algorithm. In total, more than 5,000 literature and patent sources have been found starting with the very first in the 60 s of the past century, followed by the first multiparticular products using mini-tablets with pancreatin (Panzytrat® by the former BASF subsidiary Knoll/Nordmark) authorized in 1985. There seems to be a second boost of common interest in the 2000 s when clinical studies demonstrated that one or more mini-tablets could enable superior drug administration even in very young patients including neonates over the former gold standard, a liquid drug preparation. Several pharmaceutical companies immediately started clinical development programs using the mini-tablet concept and the first products have been recently authorized by the competent authorities. Superiority was given as the mini-tablets ease the swallowing procedure compared to conventional tablets, enable various modified drug release opportunities including taste-masking by film-coating technology and provide excellent drug stability compared to liquid oral dosage forms. Due to these product attributes they are particularly beneficial to children and their caregivers. Furthermore, there is potential for precise individual drug dosing by counting adequate amounts of the multiple drug carriers. Most recently, two novel products with different concepts were authorized by the EMA and entered the market which are highlighted in this review: the first orodispersible mini-tablet with enalapril maleate for congenital heart failure (Aqumeldi® from Proveca Pharma) and the first single unit mini-tablet with matrix-type controlled melatonin release for insomnia (Slenyto® from Neurim Pharmaceuticals). Our review reveals, that the majority of the published scientific papers use co-processed, ready-to-use excipients for the orodispersible mini-tablet formulations. However, traditional fillers such as microcrystalline cellulose or lactose have also been used for immediate release mini-tablets after adding a (super)disintegrant and a lubricant. The manufacturing of mini-tablets is conducted on conventional rotary tablet presses, predominantly equipped with multi-tip toolings to improve the yield or production speed. Scaling-up has been successfully realized from compaction simulators to pilot and production scale. Film-coatings enabling gastric resistance, taste masking or sustained-release properties have been realized in both fluid-bed and drum coaters using the same polymers as for conventional tablets. There is still a significant lack in regulatory guidance despite the recent success of the mini-tablet concept, starting from suitable characterization methods in the pharmacopoeias up to the design and conduct of clinical st","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114655"},"PeriodicalIF":4.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374071","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":"Repeated sequential administration of pegylated emulsion of SU5416 and liposomal paclitaxel enhances anti-tumor effect in 4T1 breast cancer-bearing mice","authors":"Masato Maruyama ,&nbsp;Reiya Torii ,&nbsp;Hazuki Matsui ,&nbsp;Hiroki Hayashi ,&nbsp;Ken-ichi Ogawara ,&nbsp;Kazutaka Higaki","doi":"10.1016/j.ejpb.2025.114663","DOIUrl":"10.1016/j.ejpb.2025.114663","url":null,"abstract":"<div><div>To improve vascular normalization strategy for intractable triple-negative breast cancer 4T1, we examined the anti-tumor effects of repeated sequential administration of polyethylene glycol (PEG)-modified emulsion of SU5416 (PE-SU5416), a vascular endothelial growth factor (VEGF) receptor-2 kinase inhibitor, and PEG-modified liposomal paclitaxel (PL-PTX) in mice bearing 4T1 cells. Three sequential administrations (Seq×3) of PE-SU5416 and PL-PTX exhibited significantly higher anti-tumor activity than a single sequential administration (Seq×1). The tumor vasculatures were structurally normalized until after two PE-SU5416 (PE-SU5416×2) or sequential (Seq×2) administrations, while the improvement in vascular function, such as oxygen supply, blood flow, and PEG-liposomal distribution, was evident until after three administrations of PE-SU5416 (PE-SU5416×3) and Seq×3. Although some discrepancies between the structural and functional improvement in tumor vasculatures were observed after PE-SU5416×3 and Seq×3, cancer-associated fibroblasts (CAFs) and collagen levels were significantly reduced after PE-SU5416×2, PE-SU5416×3, Seq×2, and Seq×3, suggesting that a possible decrease in interstitial fluid pressure due to the reduction in CAFs and collagen would have compensated for vascular function. Furthermore, PE-SU5416×2, PE-SU5416×3, Seq×2, and Seq×3 significantly decreased tumor growth factor-β (TGF-β), an activator of CAFs, in tumor tissues, suggesting that the reduction in TGF-β levels by PE-SU5416 suppresses CAF activation.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"209 ","pages":"Article 114663"},"PeriodicalIF":4.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374068","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":"Towards a digital twin of primary drying in lyophilization using coupled 3-D equipment CFD and 1-D vial-scale simulations","authors":"Matej Zadravec ,&nbsp;Efimia Metsi-Guckel ,&nbsp;Blaz Kamenik ,&nbsp;Johan Remelgas ,&nbsp;Johannes Khinast ,&nbsp;Nick Roscioli ,&nbsp;Matthew Flamm ,&nbsp;Harshil Renawala ,&nbsp;Jeff Najarian ,&nbsp;Atul Karande ,&nbsp;Avik Sarkar","doi":"10.1016/j.ejpb.2025.114662","DOIUrl":"10.1016/j.ejpb.2025.114662","url":null,"abstract":"<div><div>A digital twin of lyophilization units was developed to facilitate the scale-up of the lyophilization process from the laboratory to the commercial scale. Our focus was on ensuring successful technology transfer for manufacture of high-quality drug products. Traditionally, lyophilization models have been specific either to the equipment or to the vial. In this study, we integrated the equipment and the vial models in a way that they mutually influenced each other via boundary conditions (two-way coupling). We conducted two sets of calculations. Firstly, we performed steady-state simulations using Computational Fluid Dynamics (CFD) to simulate an ice slab test, which helped determine the equipment capability curve. Secondly, we carried out transient, coupled simulations using a coupled 3-D CFD and 1-D vial scale simulation model to mimic the primary drying phase in a lyophilizer. Using the coupled 3-D CFD and 1-D vial scale model, we were able to determine the product temperature, the sublimation rate and the cycle time based on the temporal and spatial conditions in the lyophilizer. The coupled approach was then applied to capture the effects of process disturbances and failure conditions in the lyophilizer, which enables a more robust process design.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114662"},"PeriodicalIF":4.4,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374073","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":"Rational design of PLA-based ASDs for pharmaceutical 3D printing: Insights from phase diagram modeling","authors":"Alma Lucia Villela Zumaya ,&nbsp;Anton Iemtsev ,&nbsp;Michal Fulem ,&nbsp;Fatima Hassouna","doi":"10.1016/j.ejpb.2025.114657","DOIUrl":"10.1016/j.ejpb.2025.114657","url":null,"abstract":"<div><div>The integration of 3D printing into the pharmaceutical sciences opens new possibilities for personalized medicine. Poly(lactide) (PLA), a biodegradable and biocompatible polymer, is highly suitable for biomedical applications, particularly in the context of 3D printing. However, its processability often requires the addition of plasticizers. This study investigates the use of phase diagram modeling as a tool to guide the rational selection of plasticizers and to assess their impact on the thermodynamic and kinetic stability of PLA-based amorphous solid dispersions (ASDs) containing active pharmaceutical ingredients (APIs). Thermodynamic stability against API recrystallization was predicted based on the API solubility in PLA and Plasticizer-PLA carriers using the Conductor-like Screening Model for Real Solvents (COSMO-RS), while the kinetic stability of the ASDs was evaluated by modeling the glass transition temperatures of the mixtures. Two APIs, indomethacin (IND) and naproxen (NAP), with differing glass-forming abilities (i.e., recrystallization tendencies), and three plasticizers, triacetin (TA), triethyl citrate (TEC), and poly(L-lactide-co-caprolactone) (PLCL), were selected for investigation. The physical stability of ASD formulations containing 9 wt% API and plasticizer to PLA in two ratios, 10:81 and 20:71 w/w %, was monitored over time using differential scanning calorimetry and X-ray powder diffraction and compared with phase diagram predictions. All formulations were predicted to be thermodynamically unstable; however, those containing no plasticizer or with TEC and TA at 10 wt% were predicted to exhibit some degree of kinetic stability. Long-term physical studies corroborated these predictions. The correlation between the predicted phase behavior and long-term physical stability highlights the potential of phase diagram modeling as a tool for the rational design of ASDs in pharmaceutical 3D printing.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114657"},"PeriodicalIF":4.4,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350785","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":"Efficient nose-to-brain delivery of nine residues peptide (JAL-TA9) exhibiting hydrolytic activity against amyloid-β","authors":"Yusuke Hatakawa ,&nbsp;Akiko Tanaka ,&nbsp;Tomoyuki Furubayashi ,&nbsp;Hidemasa Katsumi ,&nbsp;Rina Nakamura ,&nbsp;Motomi Konishi ,&nbsp;Toshifumi Akizawa ,&nbsp;Toshiyasu Sakane","doi":"10.1016/j.ejpb.2025.114661","DOIUrl":"10.1016/j.ejpb.2025.114661","url":null,"abstract":"<div><div>JAL-TA9 (YKGSGFRMI), is a 9-residue catalytic peptide that cleaves amyloid β (Aβ) 42. Nasal administration was chosen to bypass the blood–brain barrier for efficient brain delivery of JAL-TA9 to treat Alzheimer’s disease (AD). Plasma clearance of JAL-TA9 after intravenous bolus injection in rats was very rapid, with a half-life of &lt;1 min. The stability of JAL-TA9 in cerebrospinal fluid (CSF) was much better than that in plasma and whole blood <em>in vitro</em>, suggesting the advantage of direct nasal delivery to avoid rapid elimination from the blood. JAL-TA9 in CSF was 0.115 μg/mL 10 min after nasal administration to rats, but below the detection limit after intravenous injection, indicating a significant direct delivery of JAL-TA9 to the brain. In mice brain, JAL-TA9 concentration was higher after nasal administration than that after intraperitoneal administration. Additionally, peak concentration in the olfactory bulb (OB) after nasal application was at 5 min, whereas in the frontal and occipital brains peaked at 30 and 60 min, respectively, suggesting sequential backward translocation of JAL-TA9 within the brain after direct transport from the nasal cavity to the OB. Therefore, nasal administration allows the efficient delivery of JAL-TA9 to the brain and may be a potential in AD treatment.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114661"},"PeriodicalIF":4.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364096","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}