European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"A comprehensive review of caffeine population pharmacokinetics in preterm infants: Factors affecting clearance","authors":"Yaodong He ,&nbsp;Xianhuan Shen ,&nbsp;Jiahao Zhu ,&nbsp;Lian Zhang ,&nbsp;Xixuan Wang ,&nbsp;Tao Zhou ,&nbsp;Jianping Zhang ,&nbsp;Wenzhou Li ,&nbsp;Xiaomei Fan","doi":"10.1016/j.ejpb.2025.114659","DOIUrl":"10.1016/j.ejpb.2025.114659","url":null,"abstract":"<div><div>Caffeine is an FDA-approved drug for preventing and treating apnea in preterm infants. However, the pharmacokinetic (PK) characteristics of caffeine in preterm infants differ significantly from those in adults. Several population pharmacokinetic (PopPK) models have been developed to investigate potential covariates influencing PK parameters. This review aimed to summarize PopPK studies of caffeine in preterm infants and explore the identified influencing covariates. It has been observed that most caffeine pharmacokinetics followed a one-compartment model (1-CMT), although one study utilized a three-compartment model (3-CMT). Various covariates including birth weight, current weight, genetic polymorphism, combination medications, feeding patterns, and pathological conditions have been identified to affect caffeine PK parameters in preterm infants. Developing an individualized dosing regimen for preterm infants is essential for safe and effective treatment. Future PopPK studies of caffeine in preterm infants should focus on sampling and feeding patterns and further explore the effects of other covariates like gestational and postnatal age on caffeine PK parameters, which should be taken into account in the individualized dosing regimen of caffeine.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114659"},"PeriodicalIF":4.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364091","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}

{"title":"β-Cyclodextrin nanosponges for the ocular delivery of therapeutic Micro-RNA in a Mouse model of retinitis Pigmentosa: A proof of concept study","authors":"Ilaria Piano ,&nbsp;Beatrice Polini ,&nbsp;Francesca Corsi ,&nbsp;Sara Carpi ,&nbsp;Giovanni Petrarolo ,&nbsp;Luca Quattrini ,&nbsp;Ilaria D’Agostino ,&nbsp;Maria Cristina Gamberini ,&nbsp;Cecilia Baraldi ,&nbsp;Grazia Chiellini ,&nbsp;Paola Nieri ,&nbsp;Concettina La Motta ,&nbsp;Claudia Gargini","doi":"10.1016/j.ejpb.2025.114660","DOIUrl":"10.1016/j.ejpb.2025.114660","url":null,"abstract":"<div><div>The exploitation of micro-RNA (miR) sequences as therapeutics has become highly attractive for the treatment of several diseases, including those still lacking effective cures such as retinitis pigmentosa (RP). Interestingly, miR-155-5p plays a role in photo-oxidative inflammation in wild-type mice and is up-regulated in rd10 mice showing peak rod degeneration, suggesting its inhibition by the corresponding anti-miR as a viable therapeutic strategy for RP. However, biomedical application of (anti-)miRs is limited by their oligonucleotide nature, suffering from low solubility and bioavailability along with a very low half-life <em>in vivo</em> due to enzymatic degradation. Thereby, the need for suitable delivery systems led to the development of various nanocarriers, including oligosaccharide-based polymers. In this context, we designed and prepared an innovative nanosponge (NS) with a β-cyclodextrin (β-CD) motif payload with a <em>bridge-like</em> molecule, the amphipathic adamantane derivative (ADM), able to establish strong interactions with both NS and the therapeutic miR, thereby delivering and eventually releasing it close to the active site. Through an <em>in vivo</em> study, we both validated the NS system as a useful tool for miR topical administration by eye drop formulation and the functional activity of anti-miR-155-5p in RP.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114660"},"PeriodicalIF":4.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364163","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":"Curcumin-loaded zein and shellac composite nanoparticles for ulcerative colitis treatment","authors":"Xiaoyan Mu ,&nbsp;Hemin Roghzai ,&nbsp;Lingwen Zeng ,&nbsp;Xiaoqiang Sun ,&nbsp;Xiubo Zhao","doi":"10.1016/j.ejpb.2025.114658","DOIUrl":"10.1016/j.ejpb.2025.114658","url":null,"abstract":"<div><div>This study highlights the efficacy of microfluidic technology in creating curcumin (Cur) loaded zein + shellac (Z + S) hybrid nanoparticles (NPs), presenting a promising avenue for enhancing Cur’s availability in the food industry, especially in beverages, and positioning it as a potent antioxidant strategy for applications such as the treatment of enteritis. The study revealed that an increase in the proportion of shellac led to a gradual increase in the particle size of Z + S NPs, while the polydispersity index (PDI) initially decreasing and then increasing. When Cur is encapsulated, an increase in the proportion of shellac resulted in a gradual decrease in particle size and PDI, accompanied by an increase in encapsulation efficiency (EE). When the ratio of zein and shellac remained constant, elevating the Cur concentration led to a gradual decrease in EE and a gradual increase in drug loading. The consistently low Zeta potential (below −20 mV) confirmed the colloidal stability of the NPs, making them suitable for prolonged storage. The NPs exhibited excellent biocompatibility with normal cells and demonstrated effective free radical scavenging capabilities. Mixing of shellac and zein regulated the release profile of Cur from the NPs, mapping the food fate in human body, enhancing the treatment efficacy of ulcerative colitis. In vivo experiment demonstrated that the NPs are able to effectively relieve the dextran sulphate sodium induced enteritis, providing a promising approach for the treatment of ulcerative colitis.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"209 ","pages":"Article 114658"},"PeriodicalIF":4.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364093","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":"Carrier-free nanodrug based on small molecule drug and sonosensitizer for enhanced the ferroptosis-driven multimodal synergistic therapy of prostate cancer","authors":"Yao-Lin Wu,&nbsp;Rui-Rui Zhao,&nbsp;Xiao Wu,&nbsp;Chun-Lei Liu,&nbsp;Chun-Zhao Liu","doi":"10.1016/j.ejpb.2025.114656","DOIUrl":"10.1016/j.ejpb.2025.114656","url":null,"abstract":"<div><div>Ferroptosis plays a significant role in overcoming the therapeutic resistance of cancer cells. Herein, a carrier-free nanoparticle based on small molecule drug sorafenib (SRF) and sonosensitizer rose bengal (RB) was constructed (named SR NPs) for ferroptosis-driven chemotherapy and sonodynamic synergistic therapy (SDT) of prostate cancer (PCa). SR NPs could be enriched in tumor cells and efficiently inhibit tumor cell proliferation. These nanodrugs could significantly reduce glutathione (GSH) synthesis, and inhibit glutathione peroxidase 4 (GPX4) expression by inhibiting the glutamate/cysteine antiporter system (System Xc^-) pathway of ferroptosis. Moreover, SR NPs-mediated ferroptosis significantly improved the amount of reactive oxygen species (ROS) generated by SDT, inhibited cell migration and adhesion, enhanced the accumulation of lipid peroxides (LPO) and augmented chemo-sonodynamic therapy. Notably, <em>in vivo</em> studies demonstrated that SR NPs enhanced tumor accumulation, exhibited good biocompatibility, and showed high anti-tumor efficacy in PC-3 tumor-bearing mice. This work offered a new strategy to enhance the treatment efficacy of prostate cancer (PCa) through ferroptosis-chemotherapy-sonodynamic synergistic therapy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114656"},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254911","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":"Exploring the physicochemical interactions and loading strategies of mesoporous silicon dioxide nanoparticles for drug delivery","authors":"Svetlana Yu. Kovtareva ,&nbsp;Eldar E. Kopishev ,&nbsp;Hongbo Zhang ,&nbsp;Sergey K. Filippov","doi":"10.1016/j.ejpb.2025.114654","DOIUrl":"10.1016/j.ejpb.2025.114654","url":null,"abstract":"<div><div>Mesoporous silica nanoparticles play an important role in drug delivery due to their high surface area, porous structure, tunable pore size, chemical stability and functionalization capability. Such properties make them a good candidate for drug encapsulation. However, molecular binding is another parameter that govern drug loading apart of pores’ structure and size. There is a lack of comprehensive reviews on that topic nowadays. This paper overviews the latest publications on the physicochemical aspects of the interaction of mesoporous silica nanoparticles with drugs. The review is focused primarily on a such parameters of the intermolecular binding between a drug and silica nanoparticle as a binding constant, enthalpy and entropy changes and experimental methods with the emphasis on the principles of thermodynamic parameters characterization. Such information would be very important for the development and optimization of drug delivery strategies based on mesoporous silica nanoparticles.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114654"},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254960","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,&nbsp;Fabian Fischer,&nbsp;Martin Hofsäss,&nbsp;Meik Ranft,&nbsp;Sophia Ebert","doi":"10.1016/j.ejpb.2025.114628","DOIUrl":"10.1016/j.ejpb.2025.114628","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"207 ","pages":"Article 114628"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","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":"OA","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,&nbsp;Adam J. Rish,&nbsp;James K. Drennen III,&nbsp;Carl A. Anderson","doi":"10.1016/j.ejpb.2025.114626","DOIUrl":"10.1016/j.ejpb.2025.114626","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"207 ","pages":"Article 114626"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","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":"Effect of protein corona on drug release behavior of PLGA nanoparticles","authors":"Damla Kelle ,&nbsp;Kai R. Speth ,&nbsp;María Martínez-Negro ,&nbsp;Volker Mailänder ,&nbsp;Katharina Landfester ,&nbsp;Banu Iyisan","doi":"10.1016/j.ejpb.2024.114611","DOIUrl":"10.1016/j.ejpb.2024.114611","url":null,"abstract":"<div><div>Poly(lactic-co-glycolide) (PLGA) nanoparticles are highly attractive for drug delivery due to their biocompatibility, biodegradability, and potential for controlled release and targeting. Despite these outstanding properties, challenges remain for clinical translation as nanomedicines. One significant factor to address is highlighting the protein corona structure and its effect on the drug release behavior. Protein corona forms upon contact with the bloodstream and influences the fate of the nanoparticles in the body. Here, we synthesize PLGA nanoparticles by miniemulsion/solvent evaporation technique, followed by the formation of protein corona on their surface using either human plasma or fetal bovine serum (FBS). Analysis by both sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry (LC-MS) reveals that dysopsonin proteins, mainly albumin, dominate the protein corona structure, suggesting prolonged blood circulation for the PLGA nanoparticles. As an anticancer drug, doxorubicin is encapsulated into PLGA nanoparticles, and <em>in vitro</em> drug release is performed at pH 7.4. While there is a minimal change in cumulative drug release after protein corona formation, our comprehensive analysis through different kinetic models shows that the protein corona alters the drug release profile of PLGA nanoparticles to a modest extent.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"207 ","pages":"Article 114611"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823811","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 ,&nbsp;Peng Yan ,&nbsp;Hailong Zhang ,&nbsp;Wenhu Zhou ,&nbsp;Jinsong Ding","doi":"10.1016/j.ejpb.2025.114633","DOIUrl":"10.1016/j.ejpb.2025.114633","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"207 ","pages":"Article 114633"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","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}