European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Molecular effects of paclitaxel-elacridar nanoemulsions in breast cancer cells: impact on uptake, cell cycle and signaling pathways","authors":"Giovanna C. Salata,&nbsp;Isabella D. Malagó,&nbsp;Giovanna Barros de Melo,&nbsp;João Agostinho Machado-Neto,&nbsp;Luciana B. Lopes","doi":"10.1016/j.ejpb.2025.114837","DOIUrl":"10.1016/j.ejpb.2025.114837","url":null,"abstract":"<div><div>In this study, we investigated how paclitaxel incorporation in a bioadhesive, hyaluronic acid-modified nanoemulsion (NE) containing the P-glycoprotein inhibitor elacridar influenced its molecular effects and mechanism of action in breast cancer cells. Incorporation of paclitaxel with elacridar in the nanoemulsion resulted in a 2.5-fold increase in cellular uptake compared to the drug solution. Clathrin-mediated endocytosis contributed to nanoemulsion-mediated cell internalization, with both paclitaxel and NBD-phosphatidylcholine (nanoemulsion surfactant) partially co-localizing with transferrin. The nanoemulsion amplified paclitaxel-mediated chromatin condensation and expression of proteins involved in apoptosis, with a 2.5-fold increase in PARP1 (Poly (ADP-ribose) polymerase 1) cleavage and a 1.7-fold downregulation of BCL2 (B-cell lymphoma protein 2) expression. Apoptosis was maintained as the main mechanism of cell death. The formulation also reduced cell migration (3-fold) compared to the solution at concentrations lower than IC₅₀, while the clonogenic effect (17-fold) was not hindered, supporting a broader impact on tumorigenesis.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114837"},"PeriodicalIF":4.3,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820971","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 effect of mRNA-lipid nanoparticle composition on stability during microneedle patch manufacturing","authors":"Sophia H. Sakers ,&nbsp;Gianna Fiduccia ,&nbsp;Katherine E. Byrne ,&nbsp;B. Pradeep K. Reddy ,&nbsp;James E. Dahlman ,&nbsp;Mark R. Prausnitz","doi":"10.1016/j.ejpb.2025.114819","DOIUrl":"10.1016/j.ejpb.2025.114819","url":null,"abstract":"<div><div>Messenger RNA (mRNA) encapsulated in lipid nanoparticles (LNPs) is a potent technology with broad applications. Microneedle patches (MNPs) can enhance the accessibility of mRNA-LNPs for vaccination or therapeutic applications. We evaluated the effects of LNP composition on the stability of mRNA-LNPs before and after MNP manufacturing, as assessed by changes in mRNA-LNP size, encapsulation efficiency, and protein expression <em>in vitro</em> and <em>in vivo</em>. The lipid molar ratio had a significant impact on LNP characteristics and ability to withstand stressors of MNP fabrication. An elevation in ionizable lipid content from 50% to 60% increased <em>in vitro</em> mRNA expression, measured by luciferase expression in RAW 264.7 cells, following extraction from an MNP. Among the three ionizable lipids tested, SM-102 had the highest expression before and after MNP manufacturing. Cholesterol analogues influenced <em>in vivo</em> expression of mRNA-LNPs before MNP manufacturing, but the effect was absent in mRNA-LNP MNPs. PEGylated lipid choice affected mRNA encapsulation in LNPs and had a strong effect on <em>in vitro</em> expression, but this effect was not seen <em>in vivo.</em> Phospholipid choice did not have a significant impact on most mRNA-LNP characteristics, but the use of DOTMA increased <em>in vitro</em> expression. These data suggest that LNP composition can affect mRNA-LNP characteristics and function both before and after MNP manufacturing. Future mRNA-LNP MNP designs should consider the effect of lipid molar ratios and favor higher ionizable lipid content.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114819"},"PeriodicalIF":4.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in auricular drug delivery for the management of different otitic conditions","authors":"Niloy Barman ,&nbsp;Sunil Kumar Sah ,&nbsp;Subhadeep Roy ,&nbsp;Santanu Kaity","doi":"10.1016/j.ejpb.2025.114836","DOIUrl":"10.1016/j.ejpb.2025.114836","url":null,"abstract":"<div><div>Millions of people suffer greatly from ear diseases, yet finding effective treatments for these conditions is a constant but frequently disregarded task, especially regarding product development and formulation design. While considerable research has focused on understanding the pathophysiology and treatment of otic diseases, relatively less attention has been paid to innovating targeted and efficient drug delivery systems. This review provides a comprehensive overview of the anatomical and physiological barriers of the ear, the spectrum of otic diseases, and currently available therapeutic approaches. Special emphasis is placed on the evolving landscape of otic drug delivery, including topical, intratympanic, and intracochlear administration routes. The manuscript critically discusses the role of advanced materials such as hydrogels, nanoparticles, and biodegradable polymers in enhancing drug residence time, permeability, and site-specific targeting within the complex inner ear environment. Furthermore, it highlights recent innovations, key challenges, such as limited drug diffusion, pharmacokinetic variability, and emerging strategies, including thermoresponsive systems and bioresponsive platforms. The review concludes by outlining future perspectives in the field, pointing toward developing minimally invasive, precisely controlled, and patient-friendly delivery systems that may revolutionize the treatment of otic diseases in the coming decades.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114836"},"PeriodicalIF":4.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798537","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":"Effects of antimicrobial preservatives on protein folding stability and subvisible particle formation in monoclonal antibody trastuzumab","authors":"Ravi Maharjan ,&nbsp;Shavron Hada ,&nbsp;I. Jeong Shin ,&nbsp;Ki Hyun Kim ,&nbsp;Nam Ah Kim ,&nbsp;Seong Hoon Jeong","doi":"10.1016/j.ejpb.2025.114835","DOIUrl":"10.1016/j.ejpb.2025.114835","url":null,"abstract":"<div><div>To prevent microbial contamination, antimicrobial preservatives need to be added in multi-dose biopharmaceuticals; however, it often introduces risks to protein stability, potentially compromising therapeutic efficacy. In this study, we investigated the effects of different preservatives (benzyl alcohol, m-cresol, phenoxyethanol, and benzalkonium chloride) on the biophysical stability of trastuzumab, a monoclonal antibody widely used for treatment of HER2 receptor-positive cancers. Among the preservatives tested, benzyl alcohol (1.0 % v/v) and m-cresol (0.3 % w/v) significantly reduced the monomeric content after 5 days of end-over-end agitation stress. Benzyl alcohol was associated with a surge in nano- to micro-sized particles (21-fold increase) and decreased thermal stability (Δ<em>T_m</em>: −5.39 °C). m-Cresol uniquely triggered visible particle formation (&gt;100 µm) within 72 h, raising concerns for injectable biologics. Benzalkonium chloride (0.01 %–0.04 % w/v) exhibited inconsistent concentration-dependent behavior, initially showing increase in subvisible aggregates before stabilizing through micelle formation at higher concentrations, albeit with irreversible secondary structural shifts toward β-sheet motifs. Conversely, phenoxyethanol (0.5 % v/v) exhibited higher compatibility, preserved the monomeric content, and suppressed particle generation to baseline levels. These findings underscore the necessity of preservative-specific compatibility assessments in formulation design for therapeutic biologics, positioning phenoxyethanol as a promising candidate for trastuzumab preservation owing to the balance between its antimicrobial efficacy and minimal destabilization.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114835"},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774972","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":"Non-invasive detection of protein aggregation in biopharmaceuticals using TD-NMR and MRI","authors":"Gozde Ozesme Taylan ,&nbsp;Hani Alam ,&nbsp;Erdem Mercan ,&nbsp;Ece Erkan ,&nbsp;Cem Yamali ,&nbsp;Mecit Halil Oztop","doi":"10.1016/j.ejpb.2025.114830","DOIUrl":"10.1016/j.ejpb.2025.114830","url":null,"abstract":"<div><div>With the rapid expansion of biotechnological drugs, ensuring their quality has become essential. Proper storage and transportation are critical to maintaining drug stability and efficacy. This study investigates protein aggregation, a major quality concern in biopharmaceuticals, using low-field NMR, Time Domain NMR and Magnetic Resonance Imaging (MRI), as a non-invasive, rapid alternative to conventional analytical methods. For the first time, MRI, T₂ relaxation times, and T₂ relaxation spectra were applied to detect aggregation in Humulin R, a low-concentration subcutaneous insulin. Aggregation was induced by heat and agitation to simulate improper handling. MRI effectively distinguished control and stressed samples, while T₂ relaxation measurements differentiated stress conditions. Additionally, T₂-Inverse Laplace Transform (<em>ILT</em>) indicated aggregate size, aligning with particle size analysis and validating the novel approach. These findings highlight the potential of low-field NMR for biopharmaceutical quality assessment.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114830"},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772695","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":"Cryoconcentration modeling and experimental measurements for freezing and thawing of a biologic bulk drug substance","authors":"Nirajan Adhikari ,&nbsp;Evgeniia Vorozhbit ,&nbsp;Petr Kazarin ,&nbsp;Gayathri Shivkumar ,&nbsp;Darryl Drake ,&nbsp;Jie Wang ,&nbsp;Mrinal Shah ,&nbsp;Sherwin Shang ,&nbsp;Alina A. Alexeenko","doi":"10.1016/j.ejpb.2025.114812","DOIUrl":"10.1016/j.ejpb.2025.114812","url":null,"abstract":"<div><div>The freezing and thawing process is a key determinant of the cryoconcentration distribution in pharmaceutical and biological bulk drug substances (BDS), which has a direct and inevitable impact on protein stability. Due to the critical influence of cryoconcentration — either stabilizing or destabilizing the protein depending on its distribution — understanding the specific mechanisms and changes occurring during freezing and thawing is essential for ensuring the stability of the BDS and, by extension, the drug product (DP). This work presents computational modeling of protein cryoconcentration induced by freezing and thawing in a two-liter plastic container. The study utilized fixed-grid modeling with a species segregation model to investigate freezing and thawing dynamics that lead to a shift in protein concentration distribution inside the container, simulating typical processing for pharmaceutical bulk drug substance. The model incorporates a partition coefficient to represent protein distribution between the BDS solution phase and the frozen ice phase. The solute (such as protein) partitioning during ice formation and gravity settlement of protein-rich liquid from the ice–liquid interface towards the bottom of a container creates cryoconcentration during freezing in an ultra-low temperature freezer. Simulations of previously frozen solution subjected to water-bath thawing at <span><math><mrow><mo>+</mo><mn>23</mn><mspace></mspace><mo>°</mo><mi>C</mi></mrow></math></span> showed a further increase of protein concentration at the bottom of the container due to the inability of the free convective currents set up during the thawing process to overcome the density based segregation. The modeling results were consistent with experimental measurements of freezing and thawing of Human serum albumin solution at 60 mg/mL in 2 L bottles, showing promise for the utilization of computational techniques to design process and equipment that reduces protein cryoconcentration and segregation gradients during freeze–thaw operation improving pharmaceutical manufacturing and product quality.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114812"},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793829","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":"Advancements in drug delivery systems for women’s reproductive health: Vaginal microbiome as a target for innovative drug delivery systems","authors":"Peace-OfonAbasi O. Bassey ,&nbsp;Margaret O. Ilomuanya ,&nbsp;Bukola A. Oseni ,&nbsp;Deborah A. Ogundemuren ,&nbsp;Karamot O. Oyediran ,&nbsp;Evans N. Ekeji ,&nbsp;Peter Abia","doi":"10.1016/j.ejpb.2025.114831","DOIUrl":"10.1016/j.ejpb.2025.114831","url":null,"abstract":"<div><div>The vaginal microbiome, predominantly made up of <em>Lactobacillus spp</em>., plays a pivotal role in women’s reproductive health, especially in dysbiosis associated with various gynecological disorders. In this comprehensive review, we discussed the current advancements in drug delivery systems targeting the vaginal microbiome, the limitations of traditional approaches, as well as explored innovative strategies in drug delivery with the vaginal microbiome as the focal point. The composition and functions of the vaginal microbiome were critically evaluated, emphasizing its significance in maintaining reproductive health. Conventional drug delivery methods, including oral, parenteral, and topical routes are faced with pharmacokinetic challenges such as poor bioavailability and limited targeted delivery. The emergence of vaginal drug delivery systems such as gels, films, rings, nanoparticulate formulations and electrospun fibers show the potential to enhance therapeutic efficacy through localized and sustained drug release. We highlighted the findings on crucial formulation considerations including physicochemical properties of drugs, excipient selection, and targeting strategies. Furthermore, we analyzed pre-clinical studies utilizing <em>in vitro</em> models including organ-on-a-chip and cell cultures, as well as <em>in vivo</em> animal models to assess the safety, efficacy, and pharmacokinetics of these innovative systems. Additionally, the review revealed that cutting-edge technologies such as electrospun fibers and 3D bioprinted scaffolds show promise for precise control over drug release kinetics and probiotic delivery. Future directions should focus on personalized approaches, ethical considerations, and patient education to fully leverage these technologies for improving women’s reproductive health outcomes globally.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114831"},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774971","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":"Insights of the controlled release effect of functional group on permeation enhancers’ enhancement capacity: A study on interaction mechanism and skin barrier function","authors":"Jiuheng Ruan ,&nbsp;Sida Liao ,&nbsp;Tang Jinye ,&nbsp;Yanyue Ou ,&nbsp;Xinyao Hu","doi":"10.1016/j.ejpb.2025.114833","DOIUrl":"10.1016/j.ejpb.2025.114833","url":null,"abstract":"<div><div>The objective of this study was to investigate the controlled release effect of various polar functional groups in acrylate pressure-sensitive adhesives (PSA) on permeation enhancers (PE), as well as to elucidate the disparities in their enhancing effects under such circumstances. The synthesis of acrylate PSA with hydroxyl group (AAOH), amide group (AACONH₂), hydroxyphenyl group (AAPhOH), and carboxyl group (AACOOH) was achieved via a solution polymerization process initiated by free radical. Gel permeation chromatography, molecular dynamic simulation and thermal analysis were conducted to characterize the properties of PSA. <em>In vitro</em> release study, Raman imaging and correlation analysis were performed to research the controlled release effect on the permeation enhancer azone (AZ). These were evaluated using a novel parameter called the control release factor (<em>F</em>_cr). The more negative the F_cr value, the stronger the control release effect<em>. In vitro</em> skin permeation study and pharmacokinetic study reflected the enhancing effects of AZ on drug ketoprofen (KET). Fourier-transform infrared spectroscopy, ¹H nuclear magnetic resonance (¹H NMR), molecular docking, rheology study, Raman spectra and solid-state nuclear magnetic resonance (ssNMR) characterized mechanisms of functional groups’ controlled release effect and the changes in skin barrier function. The results demonstrated that among the four PSA, AACOOH exhibited the most pronounced controlled release effect (<em>F</em>_cr = -45.91). This can be attributed to the formation of a robust ionic bond between AACOOH and AZ, which effectively restricted the release of AZ into the skin, resulting in minimal impact on disordering functionality of the skin barrier and enhancing drug permeation. The order of controlled release for the other three PSA on AZ was as follows: AAPhOH (<em>F</em>_cr = -43.60) &gt; AACONH₂ (<em>F</em>_cr = -40.26) &gt; AAOH (<em>F</em>_cr = -38.15), resulting the best enhancing effect attributed to AZ that released from AAOH into the skin. Besides, the interaction between the above three PSA and AZ was hydrogen bond, only the interaction of AAPhOH-AZ was a special hydrogen bond: ionic hydrogen bond. In summary, the type and strength of the interaction between PSA and PE determined the amount of PE entering the skin, thereby determining the extent to which PE disorder skin barrier function.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114833"},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772781","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":"Controlled release of curcumin and gemcitabine from mucoadhesive chitosan-gelatin polymeric ovules: Cytotoxic effects on cervical cancer cells","authors":"Oscar Alberto Alvarez-Quezada ,&nbsp;Yaresli Edaly Espino-Núñez ,&nbsp;Laura Elizabeth Valencia-Gómez ,&nbsp;Santos Adriana Martel-Estrada ,&nbsp;Norma Cesilia Arellano-Rodríguez ,&nbsp;Pablo Zapata-Benavides ,&nbsp;Claudia Lucía Vargas-Requena","doi":"10.1016/j.ejpb.2025.114834","DOIUrl":"10.1016/j.ejpb.2025.114834","url":null,"abstract":"<div><div>Cervical cancer (CxCa) is the fourth most common type of neoplasm affecting the global female population. Treatment for CxCa typically involves the systemic administration of chemotherapeutic agents. However, these treatments often result in fatigue, increased risk of infection, nausea, vomiting, hair loss, loss of appetite, and diarrhea. Therefore, it is crucial to explore new drugs and site-specific drug delivery strategies to combat cervical neoplasia. This study aimed to design vaginal suppositories based on chitosan–gelatin that enable mucoadhesion and the release of curcumin and gemcitabine and to evaluate their effects on HeLa cells. Gelatin-chitosan ovules loaded with curcumin and gemcitabine were successfully formulated. The uptake of simulated vaginal fluid (SVF) resulted in an increase in weight ranging from 40 % to 80 %. The ovules exhibited porosity<!--> <!-->and hydrophilicity and demonstrated mucoadhesive properties on porcine vaginal tissue. After 8 h of incubation at 37 °C, ovules containing 10 % gelatin released more curcumin, while those with 10 % and 20 % released more gemcitabine. Curcumin and gemcitabine exhibited cytotoxic effects on HeLa cells, with IC₅₀ values of 13.47 µM and 0.15 µM, respectively. Furthermore, it was observed that curcumin reversed gemcitabine-induced necrosis and promoted a mechanism like apoptosis or necroptosis. These findings suggest that ovules loaded with curcumin and gemcitabine can potentially serve as a site-specific treatment for CxCa.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114834"},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772696","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":"Insight in the role of resistant starch and Eudragit S 100 in a coating for controlled release in the colonic region","authors":"Sien Dedroog ,&nbsp;Jiabi Ouyang ,&nbsp;Elise Vaes ,&nbsp;Filip Willemse ,&nbsp;Sune Klint Andersen ,&nbsp;Guy Van den Mooter","doi":"10.1016/j.ejpb.2025.114818","DOIUrl":"10.1016/j.ejpb.2025.114818","url":null,"abstract":"<div><div>A dual trigger coating was designed by Ibekwe et al. to achieve site-specific delivery of therapeutics to the colon. It consists essentially of Eudragit® S 100 (EU S 100), a polymer that dissolves above pH 7, and resistant starch, which can only be degraded by enzymes produced by colonic bacteria. Both components should maintain the integrity of the coating until reaching the colonic region and ensure drug release when reaching it. The contribution of these components was investigated in the present study by permeability testing and enzymatic degradation testing of free polymer films produced using an in-house built spraying device.</div><div>Diffusion testing of EU S 100 films showed no impact of the pH (2, 4, 6) and plasticizer levels (25, 30, 35 % w/w triethyl citrate (TEC)) on the permeability of the films. The permeability of the resistant starch-Eudragit® S 100 (RS-EU S 100) films was also not affected by the pH, however, the permeability coefficient of films containing 35 % w/w TEC was significantly higher for all pH levels. Incubating the RS-EU S 100 films with enzyme resulted in a higher permeability for films with 25 % w/w TEC, yet the presence of enzyme had no effect on the permeability of 35 % w/w TEC films. For the 25 % w/w TEC films, even if EU S 100 does not dissolve (pH &lt; 7), the resistant starch in the RS-EU S 100 film can be enzymatically degraded.</div><div>Using n-butanol in the preparation process of the RS-EU S 100 films resulted in a lower permeability coefficient compared to the RS-EU S 100 films without n-butanol for all pH and plasticizer levels. n-Butanol forms a V-type complex with amylose, which makes the films less susceptible to enzymatic degradation.</div><div>The permeability and susceptibility to enzymatic degradation of the RS-EU S 100 coating can be adapted by altering the amount of plasticizer and the use of n-butanol during the production process.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114818"},"PeriodicalIF":4.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759563","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}