{"title":"Corrigendum \"The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model\" [Eur. J. Pharm. Biopharm. 94 (2015) 521-531].","authors":"Mona Alibolandi, Fatemeh Sadeghi, Khalil Abnous, Fatemeh Atyabi, Mohammad Ramezani, Farzin Hadizadeh","doi":"10.1016/j.ejpb.2024.114568","DOIUrl":"10.1016/j.ejpb.2024.114568","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114568"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544580","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}
Qing Xiao Wang, Zi Ling Li, Yan Chun Gong, Xiang Yuan Xiong
{"title":"The effects of ligand distribution and density on the targeting properties of dual-targeting folate/biotin Pluronic F127/Poly (lactic acid) polymersomes","authors":"Qing Xiao Wang, Zi Ling Li, Yan Chun Gong, Xiang Yuan Xiong","doi":"10.1016/j.ejpb.2024.114598","DOIUrl":"10.1016/j.ejpb.2024.114598","url":null,"abstract":"<div><div>Targeted drug delivery systems modified with two or more ligands were expected to have better anti-tumor ability than those with just one ligand due to the complexity and heterogeneity of tumors. Thus, dual-targeting Pluronic/poly (lactic acid) polymersomes containing biotin (BT) and folic acid (FA) ligands (BT/FA-F127-PLA) were designed to study their targeting properties over human ovarian cancer cells (OVCAR-3). Two kinds of dual-ligand targeting polymersomes, BT/FA-F127-PLA and (BT + FA)-F127-PLA, were prepared to study the effect of the dual-ligand distribution on the cell targeting of polymersomes. BT/FA-F127-PLA had two ligands distributed in the same polymersomes whereas (BT + FA)-F127-PLA had two ligands distributed in different polymersomes. The in vitro cytotoxicity and cellular uptake, and in vivo pharmacokinetic behaviors of BT/FA-F127-PLA were superior to those of (BT + FA)-F127-PLA. It suggested that biotin and folate ligands distributed on the same polymersomes could have the targeting effect of synergistic promotion. Further experiments on cell uptake mechanisms of polymersomes showed that the uptake of targeted polymersomes was associated with energy-dependent endocytosis, involving clathrin, caveolin protein, macropinocytosis and ligand receptor-mediated endocytosis. In addition, the effect of different density ratios of dual ligands for BT/FA-F127-PLA was further studied. The results showed that the cellular targeting effect of BT/FA-F127-PLA was the strongest when the molar ratio of biotin to folic acid was 7.5 %: 7.5 %. In conclusion, BT/FA-F127-PLA dual-targeting polymersomes could be good candidates as targeted drug delivery carriers.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114598"},"PeriodicalIF":4.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756974","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}
Camila Machado França de Almeida , Wendy Martin Rios , Maíra Peres Ferreira Duarte , Izaíra Tincani Brandão , Natalia Floriano Paiva , Fabiana Testa Moura de Carvalho Vicentini
{"title":"Self-assembled nanovaccine based on apoferritin: Development and vaccine regimen evaluation","authors":"Camila Machado França de Almeida , Wendy Martin Rios , Maíra Peres Ferreira Duarte , Izaíra Tincani Brandão , Natalia Floriano Paiva , Fabiana Testa Moura de Carvalho Vicentini","doi":"10.1016/j.ejpb.2024.114589","DOIUrl":"10.1016/j.ejpb.2024.114589","url":null,"abstract":"<div><div>Apoferritin-based systems have been explored last decade for their potential as vaccine delivery for viral diseases. The nanosized properties of an apoferritin-based system could increase immunogenicity, contribute to antigen stability, and reduce the vaccines’ adverse effects. The mutated extracellular portion of the epidermal growth factor receptor (EGFRvIII peptide, PEPvIII) can be applied as a specific tumoral antigen due to rare expression in normal cells. In this context, the present study proposed the development and the immunogenicity evaluation of an apoferritin-based system (AFt) to deliver a peptide vaccine for an antitumoral purpose. We developed a formulation with different PEPvIII:AFt ratios and during the association efficiency analysis, identified the dependence between the AFt concentration and the PEPvIII association percentage in the formulation. Besides, differences in the immune responses against EGFRvIII were observed depending on the PEPvIII concentration due to the different association efficiencies. Finally, the humoral immune response results showed a high antibody production against AFt, which might affect the immunological tolerance. Collectively, this study establishes the PEPvIII:AFt formulation process and highlights the determinant factors for guaranteeing vaccine safety and efficacy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114589"},"PeriodicalIF":4.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746455","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}
Xinyi Zhang , Yuelian Zhang , Huishan Zheng , Xue Yang , Shiqi Zou , Jianmin Chen
{"title":"Design, fabrication, and evaluation of antimicrobial sponge microneedles for the transdermal delivery of insulin","authors":"Xinyi Zhang , Yuelian Zhang , Huishan Zheng , Xue Yang , Shiqi Zou , Jianmin Chen","doi":"10.1016/j.ejpb.2024.114586","DOIUrl":"10.1016/j.ejpb.2024.114586","url":null,"abstract":"<div><div>Transdermal drug delivery systems hold promise, but their effectiveness is often constrained by the skin’s barrier. Microneedles (MNs) improve drug permeability by creating micro-channels in the skin, yet they continue to face challenges such as infection risks and safety concerns. To overcome these challenges, a novel antimicrobial sponge MNs (ASMNs@PVP-INS) modified with polyvinylpyrrolidone (PVP) for insulin (INS) delivery was designed. Mechanical testing demonstrated that these MNs possess excellent mechanical strength, capable of withstanding at least 0.11 N per needle without rupture. In vitro drug penetration tests revealed that the MNs consistently released over 75 % of INS within a 6 h. In an animal model, ASMNs@PVP-INS reduced initial blood glucose levels from 22.4 to 5.72 mmol/L, effectively maintaining glucose control for more than 6 h without inducing hypoglycemia. Additionally, agar diffusion assays indicated that INS loading did not compromise the antimicrobial properties of antimicrobial sponge MNs (ASMNs). Skin irritation tests showed that ASMNs@PVP-INS exhibited mild irritation (PII < 0.6), with skin damage fully recovering within 8 h. Safety assessments indicated no significant toxicity to mice, with biochemical markers remaining within normal ranges, thereby confirming their good biocompatibility. In conclusion, ASMNs@PVP-INS hold promise as a novel drug delivery vehicle.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114586"},"PeriodicalIF":4.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746456","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":"Preparation and characterization of the ground mixture of rebamipide commercial tablets and Hydroxypropyl Cellulose-SSL by ball-milling: Application to the dispersoid of mouthwash suspension","authors":"Senri Mizobuchi , Kaoru Hirose , Naoko Ishii , Yayoi Kawano , Takehisa Hanawa","doi":"10.1016/j.ejpb.2024.114584","DOIUrl":"10.1016/j.ejpb.2024.114584","url":null,"abstract":"<div><div>In the present study, to prepare dispersoids with high dispersion stability that can be used as mouthwash, ground mixtures of commercial rebamipide (RB) tablets and hydroxypropyl cellulose (HPC-SSL) samples were prepared by dry milling. The physicochemical properties of the ground mixture of HPC-SSL and the powder obtained from the preliminary ground RB tablets were then compared. The dispersoids’ physicochemical properties, dispersion stability, retention, and diffusiveness to the mucosal surfaces were evaluated <em>in vitro</em>. By co-grinding with HPC-SSL, RB transformed into fine particles around 303.6 – 361.5 nm that tended to prevent particle agglomeration in solution over time. The sample microparticles formed with HPC-SSL also avoided agglomeration on the mucosal surface for 24 h, improving oral retention. Furthermore, the ground mixture of HPC-SSL and the powder obtained from the preliminary ground RB tablets dispersed and permeated the mucus gel layer on the mucosal surface (24.2 %) but not the mucosal cells, indicating that RB remained on the mucosal surface. These results suggest that ground mixtures of commercial rebamipide (RB) tablets and hydroxypropyl cellulose (HPC-SSL) samples can be applied as a powdered suspension preparation because they showed high dispersion stability and oral mucosal retention.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114584"},"PeriodicalIF":4.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746457","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}
Peijing Yang , Qinghua Song , Lujie Zhang , Zhanqiang Liu , Haifeng Ma
{"title":"Numerical modeling and simulation for microneedles drug delivery: A novel comprehensive swelling-obstruction-mechanics model","authors":"Peijing Yang , Qinghua Song , Lujie Zhang , Zhanqiang Liu , Haifeng Ma","doi":"10.1016/j.ejpb.2024.114583","DOIUrl":"10.1016/j.ejpb.2024.114583","url":null,"abstract":"<div><div>Hydrogel microneedles have attracted significant attention in drug delivery due to their non-invasiveness and efficient administration. However, a thorough understanding of the drug transport mechanism is essential to achieve controlled drug delivery and geometry optimization of microneedles. In this study, a new swelling-obstruction-mechanics model is presented to describe the swelling and drug release behavior of hydrogel microneedles. The model integrates the swelling kinetics, the obstruction scaling of drug molecules, and the mechanical properties of hydrogel and skin and reveals the effects of swelling of the microneedle matrix and drug molecules on drug release. Subsequently, numerical simulations were conducted using the model, which enabled the optimization of hydrogel microneedle design parameters by adjusting the input variables. The results show that the geometric parameters of microneedles, especially the cross-sectional shape, have a significant effect on the drug release performance. Nevertheless, the parameters affect each other and need to be considered in the selection of a variety of factors. Additionally, penetration depth significantly affects drug release efficiency, highlighting the need for auxiliary application devices. In summary, the model advances both theoretical understanding and practical design of hydrogel microneedles, identifying key factors in drug release and optimizing their efficiency and reliability for clinical applications.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114583"},"PeriodicalIF":4.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738866","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}
Blaž Lebar , Maria Orehova , Boštjan Japelj , Ernest Šprager , Rok Podlipec , Tilen Knaflič , Iztok Urbančič , Benjamin Knez , Mitja Zidar , Jure Cerar , Janez Mravljak , Aleš Žula , Denis Arčon , Janez Plavec , Stane Pajk
{"title":"A multifaceted approach to understanding protein-buffer interactions in biopharmaceuticals","authors":"Blaž Lebar , Maria Orehova , Boštjan Japelj , Ernest Šprager , Rok Podlipec , Tilen Knaflič , Iztok Urbančič , Benjamin Knez , Mitja Zidar , Jure Cerar , Janez Mravljak , Aleš Žula , Denis Arčon , Janez Plavec , Stane Pajk","doi":"10.1016/j.ejpb.2024.114582","DOIUrl":"10.1016/j.ejpb.2024.114582","url":null,"abstract":"<div><div>The excipient selection process plays a crucial role in biopharmaceutical formulation development to ensure the long-term stability of the drug product. Though there are numerous options approved by regulatory authorities, only a subset is commonly utilized. Previous research has proposed various stabilization mechanisms, including protein-excipient interactions. However, identifying these interactions remains challenging due to their weak and transient nature. In this study, we present a comprehensive approach to identify such interactions. Using the <span><math><mrow><msup><mrow><mspace></mspace></mrow><mn>1</mn></msup><mi>H</mi></mrow></math></span> <span><math><msub><mi>T</mi><mn>2</mn></msub></math></span> CPMG (Carr-Purcel-Meiboom-Gill) filter experiment we identified interactions of rituximab with certain buffers and amino acids, shedding light on its Fc fragment instability that manifested during the enzymatic cleavage of the antibody. Moreover, chemometric analyses of 2D NMR fingerprints revealed interactions of selected excipients with antibody fragments. Furthermore, molecular dynamics simulations revealed potential interacting hotspots without NMR spectra assignment. Our results highlight the importance of an orthogonal methods approach to uncovering these critical interactions, advancing our understanding of excipient stabilization mechanisms and rational formulation design in biopharmaceutics.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114582"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686342","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}
Petra Záhonyi, Áron Gábor Müncz, Anna Péter-Haraszti, Zsombor Kristóf Nagy, István Csontos, György Marosi, Edina Szabó
{"title":"Continuous twin-screw melt granulation of drug-loaded electrospun fibers","authors":"Petra Záhonyi, Áron Gábor Müncz, Anna Péter-Haraszti, Zsombor Kristóf Nagy, István Csontos, György Marosi, Edina Szabó","doi":"10.1016/j.ejpb.2024.114580","DOIUrl":"10.1016/j.ejpb.2024.114580","url":null,"abstract":"<div><div>Electrospinning (ES) is a promising continuous formulation strategy to produce amorphous solid dispersions (ASDs) and thereby improve the dissolution of poorly water-soluble drugs. However, processing the electrospun material into solid dosage forms (e.g. tablets) is challenging due to the poor flow properties. In this research, continuous twin-screw melt granulation was applied to improve the flowability of the fibers and therefore ease the further processing steps. During this work, two ASD compositions were investigated: one containing 60 % poly-vinylpyrrolidone-vinyl acetate 6:4 copolymer and 40 % itraconazole (ITR), and another one containing hydroxypropyl methylcellulose (HPMC) and ITR in the same ratio. Both fiber compositions were granulated with polyethene glycol as the binder material, while the effects of the process parameters were examined. The application of higher granulation temperature and screw configurations with increased shear forces compromised the fibrous structure, induced crystallization of the ASD, and decreased the dissolution. However, the stability of the ITR-HPMC fibers proved to be higher as their granulation at 60 °C led to granules with adequate flow properties and dissolution. Moreover, tablets with fewer excipients were pressed from them, resulting in a 34 % reduction in weight. Consequently, this process can complement ES technology and facilitate its industrial implementation.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114580"},"PeriodicalIF":4.4,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675569","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":"Homogeneity analysis of medicine tablets by laser induced breakdown spectroscopy combined with multivariate methods","authors":"Amir Hossein Farhadian , Maedeh Mollaei","doi":"10.1016/j.ejpb.2024.114579","DOIUrl":"10.1016/j.ejpb.2024.114579","url":null,"abstract":"<div><div>Pharmaceutical tablets need to have a homogenous chemical structure, especially in cases where the patient may divide the tablet in half prior to consumption. This work aims to demonstrate the viability of using laser induced breakdown spectroscopy (LIBS) for analyzing the homogeneity and determining the chemical composition of losartan potassium tablets. This was accomplished by obtaining the spectra of 10 tablet points in 30 successive laser pulses, which revealed four main peaks (C, H, N, and O) as well as a high concentration of calcium and potassium in the core tablets and titanium in the coating—all of which are excellent analytical objectives for LIBS. It is possible to say that the generated plasma meets the minimum requirement for local thermodynamic equilibrium because the physical parameters of the plasma, including temperature (T) and electronic density (N<sub>e</sub>), were calculated throughout the Boltzmann plot and Stark broadened line, respectively, and the McWhirter criterion was met. In addition, T and N<sub>e</sub> changes have been used for homogeneity analysis. Different peak comparisons cannot provide us with further data because the major structural components are similar, making it challenging to differentiate between them. So relative standard deviation (RSD) and principal component analysis (PCA) were used to comprise the whole spectra, which showed that the homogeneity of the tablet’s core is better than that of the coating and is acceptable.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114579"},"PeriodicalIF":4.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638707","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}
Sabrina S. Snyder, Crystal A. Rock, Nancy J. Millenbaugh
{"title":"Antifungal peptide-loaded alginate microfiber wound dressing evaluated against Candida albicans in vitro and ex vivo","authors":"Sabrina S. Snyder, Crystal A. Rock, Nancy J. Millenbaugh","doi":"10.1016/j.ejpb.2024.114578","DOIUrl":"10.1016/j.ejpb.2024.114578","url":null,"abstract":"<div><div>Invasive fungal infections have high mortality rates, and many current antimycotics are limited by host toxicity and drug resistance. Recent experiments in our laboratory have demonstrated the antifungal activity of dKn2-7, a synthetic peptide, against <em>Candida albicans</em>. The purpose of the current study was to develop a wound dressing capable of dKn2-7 release for extended periods to help combat fungal infection in wounds. dKn2-7 was incorporated into calcium alginate microfibers, an excipient with known wound healing and hemostatic properties. dKn2-7 release rates from the fibers were dependent on drug loading, but all formulations exhibited a burst release with 41–71 % of total theoretical release in the first 15 min and 84–96 % release by 24 h. Calcium release at 15 min was similar to that of a commercial hemostatic dressing, indicating dKn2-7 loading would not adversely affect the hemostatic capability of the alginate fibers. <em>In vitro</em> antifungal studies indicated a dose dependent effect with fibers loaded at ≥20 µg/mg causing significant planktonic killing and ≥30 µg/mg causing significant biofilm killing. Viable fungal counts in biofilms grown on <em>ex vivo</em> porcine skin declined by 99 % following 500 µg/mg fiber treatment. Skin histology indicated no significant differences in tissue damage between treatment groups and controls. Results confirm calcium alginate microfibers are capable of binding and subsequently releasing dKn2-7 over a 24-h period when rehydrated. Furthermore, dKn2-7 released from the fibers was able to significantly reduce biofilms in an <em>ex vivo</em> model with minimal toxicity, indicating these dKn2-7-loaded fiber dressings may be effective at controlling <em>C. albicans</em> biofilm infections <em>in vivo</em>.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114578"},"PeriodicalIF":4.4,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617176","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}