European Journal of Pharmaceutical Sciences最新文献

{"title":"Model-informed drug development of Mim8 – a next-generation bispecific antibody for treatment of haemophilia A","authors":"Mads Kreilgaard, Irina Matytsina, Paula Persson","doi":"10.1016/j.ejps.2025.107162","DOIUrl":"10.1016/j.ejps.2025.107162","url":null,"abstract":"<div><h3>Background</h3><div>Haemophilia A is a congenital bleeding disorder caused by deficiency of clotting factor VIII (FVIII). Mim8 (denecimig) is a next-generation activated FVIII mimetic bispecific antibody under phase 3 investigation for subcutaneous management of haemophilia A with or without FVIII inhibitors. Mim8 uses tiered dosing, which is a novel dosing approach in haemophilia where patients receive a fixed dose according to which body weight range they fall into and their chosen dosing frequency, reducing the need for dose calculations and potentially reducing treatment wastage.</div></div><div><h3>Objectives</h3><div>This study aimed to establish the early population pharmacokinetics (PK) and PK/pharmacodynamic (PD) properties of Mim8 using both biomarker and clinical endpoint data. Models were used to inform drug-development decisions using trial simulations and transform the dosing strategy in haemophilia to a novel simplified treatment option using tiered dosing in paediatric and adult populations.</div></div><div><h3>Patients/Methods</h3><div>Data from 129 participants exposed to Mim8 in the phase 1 PK trial (NCT0512747) and the FRONTIER1 trial (NCT04204408) were used to develop population PK and PK/PD models for thrombin generation and treated bleeds. The models were used for trial simulations to optimise dosing regimens evaluating Mim8 exposure, biomarker and clinical endpoint targets on a population level (paediatric and adolescent/adult) and on a typical subject level for the range of body weight (BW) in the trial. Clinical endpoint targets were set to: (1) at least 70 % of patients without treated bleeds in a 6-month trial on a population level and >95 % reduction in relative bleed risk on a typical subject level across all weight ranges and dosing frequencies, and (2) sustained peak Mim8 exposure below highest exposure observed in phase 1/2 trials.</div></div><div><h3>Results</h3><div>The population PK of Mim8 were best described with a structural two-compartment model with baseline BW as the most significant covariate for Mim8 exposure. Both peak thrombin response and Mim8 effect on bleed risk were best described with a direct link PK/PD model with an E<sub>max</sub> response. Model-estimated EC<sub>50</sub> was 2.03 µg/mL for peak thrombin and 0.07 µg/mL for bleed risk. Using trial simulations, tiered dosing in three weight ranges (<15, 15–<45, and ≥45 kg) was identified to reach the clinical endpoint targets and maximum desired exposure for all three dosing frequencies: once every week, once every 2 weeks, and once every month. This was done with an initial one-time loading dose establishing steady-state conditions within the first day, followed by maintenance doses at the desired dosing frequency. Loading and maintenance doses for the nine combinations of weight ranges and dosing frequencies were covered by five dose presentations. Ongoing phase 3 trials have been based on the dosing strategy presented here.<","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107162"},"PeriodicalIF":4.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic interaction between SHR2554 and fluconazole: A single-center, open-label and one-sequence crossover phase I trial in healthy Chinese subjects","authors":"Yuyang Dai ,&nbsp;Minwan Hu ,&nbsp;Shaojie Guo ,&nbsp;Feng Wu ,&nbsp;Ying Han ,&nbsp;Siyang Ni ,&nbsp;Shaorong Li ,&nbsp;Zhenyu Zhu ,&nbsp;Weilan Yuan ,&nbsp;Xiuli Zhao","doi":"10.1016/j.ejps.2025.107163","DOIUrl":"10.1016/j.ejps.2025.107163","url":null,"abstract":"<div><div>SHR2554, a highly selective oral EZH2 inhibitor, shows promise in treating hematologic malignancies. However, its metabolism via CYP3A4 raises concerns about drug-drug interactions. This study evaluates the impact of fluconazole, a moderate CYP3A4 inhibitor, on the pharmacokinetics and safety implications of SHR2554. We conducted a single-center, open-label, single-dose, single-sequence crossover phase I trial. 18 Chinese healthy subjects were orally administered SHR2554 100 mg on Day 1, fluconazole 400 mg on Day 4 and 200 mg QD from Days 5 to 6. SHR2554 100 mg co-administrated with fluconazole 200 mg on Day 7, and fluconazole 200 mg QD from Days 8 to 9. Pharmacokinetic parameters were compared after subjects were administered SHR2554 alone and in combination with fluconazole. C_max, AUC_0-t, and AUC_0-∞ were significantly increased when SHR2554 was co-administered with fluconazole. The co-administration led to a 3.29-, 4.79-, and 4.13-fold increase in C_max, AUC_0-t, and AUC_0-∞, respectively. Safety evaluations indicated that the observed treatment-emergent adverse events were mild and transient. These findings underline the necessity of caution when co-administered SHR2554 with moderate CYP3A4 inhibitors in clinical settings, providing crucial insights for optimizing future clinical trials.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107163"},"PeriodicalIF":4.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guiding excipient selection for physically stable amorphous solid dispersions: A combined in-vitro in-silico approach","authors":"Egis Zeneli ,&nbsp;Hugo Bohets ,&nbsp;Frédéric Ngono Mebenga ,&nbsp;René Holm ,&nbsp;Christophe Tistaert ,&nbsp;Martin Kuentz","doi":"10.1016/j.ejps.2025.107152","DOIUrl":"10.1016/j.ejps.2025.107152","url":null,"abstract":"<div><div>Fast screening of amorphous solid dispersions (ASDs) is a need in the pharmaceutical industry. To support this, several emerging technologies have been developed ranging from in-silico prediction to miniaturized high-throughput experimentation. However, a notable challenge lies in the absence of comparative data. In the present work, a combination of a miniaturized screening of ASDs with calculation of activity coefficients using the conductor like screening model for real solvents (COSMO-RS) was proposed. First, the physical stability of ASDs comprising drugs of different glass forming ability (GFA) each with ten pharmaceutically relevant polymers was evaluated under accelerated stress conditions at two drug:polymer ratios. The miniaturized high-throughput screening method was based on the instability onset time that was monitored by polarized light microscopy (PLM). Furthermore, COSMO-RS was used to assess the interaction strength between the drugs and polymers by calculating activity coefficients, which was combined with estimations of the wet glass transition temperature (T_g), to account for molecular mobility. The computational calculations showed an overall alignment of 87 % with the instability of the ASDs observed experimentally for comparable drug:polymer ratios and humidity conditions. This positive result supports the current understanding of stable ASD formulation where at given ambient conditions, a low molecular mobility as well as the strength of interaction between drug and polymer has a main impact on the physical stability of ASDs. The current results are further encouraging to implement such a combined in-vitro/high-throughput (HTS) and in-silico strategy in early industrial screening of ASDs.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107152"},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodegradable nanofibrous pharmaceutical-eluting stents for finger joint reconstruction","authors":"Yung-Heng Hsu ,&nbsp;Ying-Chao Chou ,&nbsp;Chia-Ching Huang ,&nbsp;Yi-Hsun Yu ,&nbsp;Shih-Jung Liu","doi":"10.1016/j.ejps.2025.107158","DOIUrl":"10.1016/j.ejps.2025.107158","url":null,"abstract":"<div><div>Reconstructing small joints is a complex and challenging process that can result in graft-associated complications, primarily owing to the unsatisfactory function of currently used silastic material and the induction of adverse host reactions. This work addresses this issue by developing a solution-extrusion additively manufactured polycaprolactone (PCL) tubular mesh stents integrated with electrospun nanofibers containing prednisone- and ketorolac-loaded poly(lactic-co-glycolic acid) (PLGA). The mechanical performance of PCL stents and the drug release profiles of pharmaceuticals from spun nanofibers were evaluated. The results indicate that the manufactured PCL stents exhibit excellent mechanical strength and fatigue resistance. Furthermore, the drug-releasing nanofibers effectively eluted prednisone and ketorolac for over 30 days in vitro. In vivo tests on a rabbit knee model demonstrated sustained pharmaceutical release for &gt;42 days. Animals that received the degradable drug-loaded stent exhibited the highest activity levels. These findings indicate that hybrid bioresorbable drug-eluting stents with extended prednisone and ketorolac release have potential applications in small joint arthroplasty.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107158"},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial community structure and dominant species in pharmaceutical manufacturing water revealed by high-throughput sequencing","authors":"Saori Shikama ,&nbsp;Kimiko Uchii ,&nbsp;Makoto Sadamitsu ,&nbsp;Takashi Kaminagayoshi ,&nbsp;Yoshihiko Koizumi ,&nbsp;Masao Nasu","doi":"10.1016/j.ejps.2025.107153","DOIUrl":"10.1016/j.ejps.2025.107153","url":null,"abstract":"<div><div>Control of the microbiological quality of water for pharmaceutical manufacturing is essential to ensure the safety of pharmaceutical products. A major issue in the quality control of pharmaceutical manufacturing water is the time required to identify microbial contaminants, which can be as long as several days using traditional culture methods. Here, we demonstrate the use of high-throughput sequencing of samples taken from a pharmaceutical water production system, using the Oxford Nanopore Technologies MinION sequencing platform. We successfully revealed the bacterial community structure and dominant species in stagnation sampling ports of the pharmaceutical water supply system. Dynamic changes in dominant bacteria were detected across different treatment stages: <em>Phreatobacter</em> in the city water, <em>Methylobacterium</em> in the reverse osmosis-treated water (&gt;95 % of the bacterial abundance) and <em>Ralstonia</em> in the ultrafiltration-treated water (&gt;93 % of the bacterial abundance). Compared with traditional culture methods, the MinION sequencing approach enabled rapid characterization of bacterial composition and prompt identification of dominant species. This cost-effective, molecular-based approach will usher in a new era of bioburden monitoring and identification in pharmaceutical water systems, in line with regulatory recommendations to implement rapid microbiological methods. Our findings demonstrate the practical application of high-throughput sequencing for comprehensive bacterial analysis in the pharmaceutical industry.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107153"},"PeriodicalIF":4.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of therapeutic drug monitoring on microbiological eradication in patients with staphylococcus aureus bacteremia","authors":"Meng-Yu Kong ,&nbsp;Sun-Ting Qin ,&nbsp;Rui-Yun Ling ,&nbsp;Qing Chen ,&nbsp;Jing Fu ,&nbsp;Yao-Jie Chen ,&nbsp;Yu-Han Zeng ,&nbsp;Dan-Na Jiang ,&nbsp;Guan-Yang Lin ,&nbsp;Xiu-Hua Zhang ,&nbsp;Xu-Ben Yu","doi":"10.1016/j.ejps.2025.107154","DOIUrl":"10.1016/j.ejps.2025.107154","url":null,"abstract":"<div><div>This study aims to investigate the impact of therapeutic drug monitoring (TDM) on the microbiological eradication rate in patients with <em>Staphylococcus aureus</em> bacteremia. Demographic information and laboratory data were collected for patients who were diagnosed with <em>Staphylococcus aureus</em> bacteremia during their hospital stays from January 2021 to May 2024. A total of 105 patients were included in the TDM group and 208 patients in the non-TDM group. The Chi-squared test showed a significantly higher microbiological eradication rate in the TDM group compared to the non-TDM group before (<em>p</em> <em>&lt;</em> <em>0.001</em>) and after (<em>p</em> <em>=</em> <em>0.003</em>) propensity score matching. Subgroup analysis showed that the eradication rate was significantly higher in the TDM group for patients with either methicillin-sensitive <em>Staphylococcus aureus</em> bacteremia (<em>p</em> <em>&lt;</em> <em>0.001</em>) or methicillin-resistant <em>Staphylococcus aureus</em> bacteremia (<em>p</em> <em>=</em> <em>0.007</em>). Moreover, for patients with multi-site infections, the microbiological eradication rate was significantly higher in the TDM group for either methicillin-sensitive <em>Staphylococcus aureus</em> bacteremia (<em>p</em> <em>&lt;</em> <em>0.001</em>) or methicillin-resistant <em>Staphylococcus aureus</em> bacteremia (<em>p</em> <em>&lt;</em> <em>0.001</em>). Although the drugs undergoing TDM in this study-vancomycin, daptomycin, linezolid, and teicoplanin-are primarily used for treating methicillin-resistant <em>Staphylococcus aureus</em> bacteremia, TDM for these agents can also significantly improve the microbiological eradication rate in methicillin-sensitive <em>Staphylococcus aureus</em> bacteremia. Furthermore, multivariate logistic regression analysis confirmed that TDM is an independent protective factor for microbiological eradication rate (<em>p</em> <em>&lt;</em> <em>0.001</em>). In conclusion, this study demonstrates that performing TDM in patients with <em>Staphylococcus aureus</em> bacteremia can indeed enhance the microbiological eradication rate, thereby improving patient outcomes.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107154"},"PeriodicalIF":4.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A peptide mimetic therapeutic strategy targeting dysfunction of the scaffold protein DISC-1 in psychiatric disorders","authors":"Abhishek Cukkemane ,&nbsp;Andrew J. Dingley ,&nbsp;Jeannine Mohrlüder ,&nbsp;Beatrix Santiago-Schübel ,&nbsp;Oliver H. Weiergräber ,&nbsp;Dieter Willbold","doi":"10.1016/j.ejps.2025.107148","DOIUrl":"10.1016/j.ejps.2025.107148","url":null,"abstract":"<div><div>Disrupted in schizophrenia 1 (DISC1) is a scaffold protein that regulates several physiological processes ranging from cellular division to neurodevelopment, and its dysfunction contributes to various neurological disorders including schizophrenia, bipolar and mood disorders, and autism. Thus, deciphering its native functions and pathophysiological roles is crucial. In this report, three disease-associated mutants of the C-region of DISC1, i.e., S713E, S704C, and L807-frameshift, were examined to further elucidate the role of DISC1 in cell division. We demonstrate that the mutations do not render the variants functionally inactive; instead, the interaction sites are presumably lost during the aggregation of the DISC1 C-region into amyloid-type fibrils. The minimal fibrillizing element in the C-region is the intrinsically disordered β-core (716‒761) that houses a segment absent in the splice variant DISC1^Δ22aa, which cannot bind proteins of the mitotic spindle complex and thus hampers cellular proliferation. Based on these structure-function relationships, we present a rational drug development strategy using phage display technology and highlight the role of peptide mimetics in curtailing the agglomeration of fibrils.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107148"},"PeriodicalIF":4.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dumping test: In vitro predictive tool for bioequivalence of Telmisartan formulations","authors":"Martha Cossio ,&nbsp;Barbara Sanchez-Dengra ,&nbsp;Alejandro Ruiz-Picazo ,&nbsp;Mirna Fernandez-Cervera ,&nbsp;Miguel-Angel Cabrera-Perez ,&nbsp;Marta González-Alvarez ,&nbsp;Isabel González-Alvarez ,&nbsp;Marival Bermejo","doi":"10.1016/j.ejps.2025.107147","DOIUrl":"10.1016/j.ejps.2025.107147","url":null,"abstract":"<div><h3>Background</h3><div>The \"dumping\" test is a simple dynamic dissolution methodology widely studied as a useful tool in bioequivalence trials for class II drug products.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate the dumping test as an in vitro method to predict the in vivo behavior of Telmisartan formulations. A one-step level A IVIVC was developed for three immediate-release formulations (Micardis® as the reference and two generics, X1 and X2) using this transfer model.</div></div><div><h3>Methods</h3><div>Dumping tests were performed by placing drug products in 20 mL of HCl 0.01 N and sampling for 20 min at 37 °C in an orbital shaker. The contents were then transferred to a USP 2 apparatus with 480 mL of pH 6.8 phosphate buffer, maintaining 37 °C and 50 rpm stirring. Bioequivalence was assessed using the similarity factor f2.</div></div><div><h3>Results</h3><div>The f2 values were 46.47 between REF and NBE (non-similar) and 57.43 between REF and BE (similar). The IVIVC study confirmed a level A correlation, supporting the in vitro dissolution results.</div></div><div><h3>Conclusions</h3><div>The dynamic dissolution dumping test proved to be a valuable tool for studying the complex in vivo dissolution process of Telmisartan immediate-release formulations.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107147"},"PeriodicalIF":4.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting the tabletability of binary powder mixtures from that of individual components","authors":"Vedant Girish Bhagali,&nbsp;Gerrit Vreeman,&nbsp;Aakash Hasabnis,&nbsp;Changquan Calvin Sun","doi":"10.1016/j.ejps.2025.107151","DOIUrl":"10.1016/j.ejps.2025.107151","url":null,"abstract":"<div><div>Predicting the tabletability, i.e., the relationship between tensile strength and compaction pressure, of powder mixtures based on that of pure materials would streamline tablet formulation development, saving both time and materials. This would be a significant step toward achieving digital tablet formulation design. The recently derived Vreeman-Sun tabletability equation enables the mathematical description of tabletability data using three parameters: <span><math><msub><mi>σ</mi><mrow><mi>m</mi><mi>a</mi><mi>x</mi></mrow></msub></math></span>, <span><math><mi>α</mi></math></span>, and <span><math><mi>β</mi></math></span>. Therefore, tabletability prediction is achieved by predicting these three tabletability parameters. In this work, we developed a strategy to predict mixture tabletability parameters based on those of the individual components, employing an appropriate mixing rule. Using materials with diverse mechanical properties, we demonstrate that the power-law mixing rule overall outperforms both the linear and harmonic mixing rules in predicting mixture tabletability parameters, leading to excellent agreement with experimental tabletability profiles.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107151"},"PeriodicalIF":4.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phospholipid acyl chain length modulation: a strategy to enhance liposomal drug delivery of the hydrophobic bacteriocin Micrococcin P1 to biofilms","authors":"Ahmed M. Amer ,&nbsp;Colin Charnock ,&nbsp;Kirill V. Ovchinnikov ,&nbsp;Tage Thorstensen ,&nbsp;Sanko Nguyen","doi":"10.1016/j.ejps.2025.107149","DOIUrl":"10.1016/j.ejps.2025.107149","url":null,"abstract":"<div><div>This study describes the development of fusogenic liposomes as a drug delivery system for the hydrophobic antimicrobial peptide micrococcin P1 (MP1). The liposomes were formulated using phospholipids with varying acyl chain lengths, with the goal of improving biofilm eradication. Entrapment of MP1 in liposomes effectively improved its stability in solution, as demonstrated by liquid chromatography-mass spectrometry monitoring over a two-month period. Liposomal entrapment lowered the minimum inhibitory concentration of MP1 against several <em>Staphylococcus aureus</em> strains, including clinical isolates, by 4- to 16-folds. Increasing the phospholipid acyl chain length (16-carbon to 20-carbon) in the liposomal composition, resulted not only in an improved entrapment of MP1, but also higher antibiofilm activity. Confocal laser scanning microscopy imaging revealed that the MP1-loaded liposomal effect was likely due to disruption of the biofilm matrix. At a concentration of 0.25 µg/mL, MP1 loaded in 1,2-diarachidoyl-sn‑glycero-3-phosphocholine (DAPC)-based fusogenic liposomes reduced biofilm cell viability by approximately 55 %, compared to only 15 % with free MP1 equivalents. However, the increased liposomal bilayer hydrophobicity via the longer acyl chains compromised the physical stability of the fusogenic liposomes. While MP1-loaded liposomes based on the shorter 16-carbon acyl chain 1,2-dipalmitoyl-sn‑glycero-3-phosphocholine (DPPC) remained stable for two months, the DAPC liposomes were only stable for two weeks. The physical stability was improved by increasing the concentration of the cationic phospholipid, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), from 25 mol % to 50 mol % in the liposomal composition. Overall, these findings highlight the potential of liposomal systems for delivering hydrophobic peptides like MP1 to <em>Staphylococcus aureus</em> biofilms, offering promise for improving the treatment of biofilm-associated infections.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107149"},"PeriodicalIF":4.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}