European Journal of Pharmaceutical Sciences最新文献

{"title":"Local delivery of lipid-based nanoparticles containing microbial nucleic acid for osteoimmunomodulation","authors":"N.R. Rahmani ,&nbsp;F. Jahanmard ,&nbsp;A. Hassani Najafabadi ,&nbsp;J. Flapper ,&nbsp;O. Dogan ,&nbsp;A. Khodaei ,&nbsp;G. Storm ,&nbsp;M. Croes ,&nbsp;M.C. Kruyt ,&nbsp;D. Gawlitta ,&nbsp;H. Weinans ,&nbsp;E. Mastrobattista ,&nbsp;S. Amin Yavari","doi":"10.1016/j.ejps.2025.107050","DOIUrl":"10.1016/j.ejps.2025.107050","url":null,"abstract":"<div><div>Osteoimmunomodulation is a strategy to promote bone regeneration in implants by modifying the immune environment. CpG-containing oligonucleotides type C (CpG ODN C) and Polyinosinic:polycytidylic acid (Poly[I:C]) are analogs of microbial nucleic acids that have been studied for various immunotherapeutic applications. This research investigates the potential of CpG ODN C and Poly(I:C) as an osteoimmunomodulatory agent for bone regenerative purposes. We encapsulated each nucleic acid in a lipid-based nanoparticle to facilitate the delivery into intracellular pathogen recognition receptors in immune cells. The lipid-based nanoparticles were ±250 nm in size with a negative charge (−36 to −40 mV) and an encapsulation efficiency of ±60 %. Lipid-based nanoparticles containing nucleic acids, Lip/CpG ODN C and Lip/Poly(I:C), increased the production of TNF, IL-6, and IL-10 by primary human macrophages compared to free-form nucleic acids. Conditioned medium from macrophages treated with CpG ODN C (10 µg/ml) and Lip/CpG ODN C (0.1, 1, and 10 µg/ml) promoted osteoblast differentiation of human mesenchymal stromal cells by 2.6-fold and 3-fold, respectively; no effect was seen for Lip/Poly(I:C). Bone implants were prepared, consisting of a biphasic calcium phosphate scaffold, bone morphogenetic protein (BMP) 2, and lipid-based nanoparticles suspended in gelatin methacryloyl (GelMA) hydrogel. Implants were evaluated for <em>de novo</em> bone formation in an extra-skeletal implantation model in rabbits for 5 weeks. Based on the particles suspended in GelMA, six groups of implants were prepared: Lip/CpG ODN C, Lip/Poly(I:C), Lip (empty), CpG ODN C, Poly(I:C), and a control group consisting of empty GelMA. After 5 weeks, healthy bone tissue formed in all of the implants with active osteoblast and osteoclast activity, however, the amount of new bone volume and scaffold degradation were similar for all implants. We suggest that the working concentrations of the nucleic acids employed were inadequate to induce a relevant inflammatory response. Additionally, the dosage of BMP-2 used may potentially mask the immune-stimulatory effect. Lip/CpG ODN C holds potential as a bioactive agent for osteoimmunomodulation, although further <em>in vivo</em> demonstration should corroborate the current <em>in vitro</em> findings.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107050"},"PeriodicalIF":4.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the photothermal properties of indocyanine green in melanoma spheroids via encapsulation in Span 80-containing lipid nanocapsules","authors":"Siyang Wu ,&nbsp;Taher Hatahet ,&nbsp;Wafa' T. Al-Jamal","doi":"10.1016/j.ejps.2025.107049","DOIUrl":"10.1016/j.ejps.2025.107049","url":null,"abstract":"<div><div>Indocyanine green (ICG), a well-known photosensitiser, has shown potential in photothermal therapy (PTT) for cancer treatment, but its effectiveness is limited by poor skin penetration and rapid clearance. To address this, lipid nanocapsules (LNCs) were used as nanocarriers to enhance ICG's cellular uptake and photothermal (PT) performance in melanoma cells. Utilising our recently developed Span 80-modified LNCs (LNC100-S8) with high biocompatibility and enhanced cellular uptake in B16F10 melanoma cells, ICG was loaded into LNC100-S8 using the phase inversion temperature method. The results showed that ICG encapsulation at 4.5 mg/mL maintained small LNC sizes (95–105 nm). Moreover, the heating capacity of ICG in LNCs was approximately 1.5 times higher than free ICG, achieving temperature increases over 10 °C post-irradiation. In cell cancer monolayers, LNC100-S8 enhanced ICG uptake by 1.5 times compared to free ICG and reduced cell viability to 50 % following 808 nm laser irradiation. More promisingly, ICG-LNC100-S8 combined with laser irradiation significantly reduced three-dimensional B16F10 spheroids size up to 11 days post-treatment compared to free ICG. Overall, our findings validate LNC100-S8, as promising nanocarriers for enhancing ICG-based PTT, supporting their potential applications <em>in vivo</em> to treat melanoma and other skin cancers.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107049"},"PeriodicalIF":4.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-type OATP1B3-V1 is a functional plasma membrane transporter mediating increased uptake of chemotherapeutics in vitro and in vivo","authors":"Éva Bakos ,&nbsp;Virág Bujdosó-Székely ,&nbsp;Izabel Patik ,&nbsp;Laura Király ,&nbsp;Tamás Langó ,&nbsp;Eszter Kozák ,&nbsp;Mihály Cserepes ,&nbsp;József Tóvári ,&nbsp;Csilla Özvegy-Laczka","doi":"10.1016/j.ejps.2025.107046","DOIUrl":"10.1016/j.ejps.2025.107046","url":null,"abstract":"<div><div>Cancer-type Organic anion transporting polypeptide 1B3, ct-OATP1B3-V1 is a tumor-specific isoform of liver-type OATP1B3 (Lt-OATP1B3). Ct-OATP1B3-V1 is identical with liver-specific Lt-OATP1B3 except it lacks the first 28 amino acids. Although there is a growing interest in using this isoform as a biomarker for colorectal cancer, available data regarding cellular localization and function of ct-OATP1B3-V1 remains controversial. The main objective of our study was to clarify the localization and function of ct-OATP1B3-V1 <em>in vitro</em> and <em>in vivo,</em> and to investigate its role in chemotherapy sensitivity. For this aim, A431 and HCT-8 carcinoma cell lines overexpressing ct-OATP1B3-V1 were generated. With the help of these cell lines, localization and activity of ct-OATP1B3-V1 as well as its effect on chemotherapy sensitivity was examined both <em>in vitro</em> and <em>in vivo</em>. We found that ct-OATP1B3-V1 is a functional plasma membrane transporter that sensitizes the cells toward various chemotherapeutics, including docetaxel, oxaliplatin and capecitabine metabolites <em>in vitro</em>. Increased sensitivity to docetaxel and capecitabine of ct-OATP1B3-V1 expressing cells was also confirmed in <em>in vivo</em> experiments performed on A431-V1 derived xenografts. However, due to the apparent proliferative advantage of V1-expressing xenografts over the mock-transfected control, they could not be completely eradicated by either docetaxel or capecitabine treatment. Our results demonstrate that while ct-OATP1B3-V1 can be exploited to inhibit tumor growth, this strategy alone is likely insufficient for complete tumor elimination, possibly due to the more complex <em>in vivo</em> functions of ct-OATP1B3-V1.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107046"},"PeriodicalIF":4.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A physiologically based biopharmaceutics modeling (PBBM) framework for characterizing formulation-dependent food effects: Paving the road towards fed state virtual BE studies for itraconazole amorphous solid dispersions","authors":"Niklas Rudolph ,&nbsp;Nitin Charbe ,&nbsp;David Plano ,&nbsp;Abdullah Al Shoyaib ,&nbsp;Arindom Pal ,&nbsp;Heather Boyce ,&nbsp;Liang Zhao ,&nbsp;Fang Wu ,&nbsp;James Polli ,&nbsp;Jennifer Dressman ,&nbsp;Rodrigo Cristofoletti","doi":"10.1016/j.ejps.2025.107047","DOIUrl":"10.1016/j.ejps.2025.107047","url":null,"abstract":"<div><div>This study leverages physiologically based biopharmaceutics modeling (PBBM) to predict the clinical performance of two itraconazole (ITRA) amorphous solid dispersions (ASDs), Sempera® and Tolsura®, under fasted and fed state conditions, exploring the potential of PBBM in predicting formulation-specific food interactions. The ITRA formulations were subjected to extensive <em>in vitro</em> biopharmaceutical testing, including solubility studies and dissolution tests under fasted and fed state conditions, revealing significant differences in dissolution behaviors between Sempera® and Tolsura®. The impact of food and hypochlorhydria on drug absorption was evaluated using a stepwise mechanistic deconvolution-reconvolution PBBM approach, integrating fundamental parameters based on the <em>in vitro</em> data into the final model. Our model not only successfully predicted the effects of acid reducing agents (ARA) and food on the oral absorption of ITRA, but also captured the between-subject variability, demonstrating the utility of this approach in understanding the complex interplay between drug, formulation, and gastrointestinal environment. Most importantly, the PBBM was able to accurately predict the positive impact of food on the absorption of Sempera® and the negative food effect of Tolsura®. The findings highlight the importance of considering formulation characteristics and gastrointestinal physiology, underscoring the potential of PBBM in bioequivalence (BE) assessment of generic formulations under varying physiological conditions, including in the fed state and in hypochlorhydric patients. The successful application of this stepwise and mechanistic PBBM approach suggests a potential pathway for streamlining drug development and may contribute to more informed decision-making for BE assessment.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107047"},"PeriodicalIF":4.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin in diabetic kidney disease patients with different filtration status","authors":"Yang Yang ,&nbsp;Manna Li ,&nbsp;Honghong Zou ,&nbsp;Pingping Yang ,&nbsp;Li Wang ,&nbsp;Gaosi Xu","doi":"10.1016/j.ejps.2025.107045","DOIUrl":"10.1016/j.ejps.2025.107045","url":null,"abstract":"<div><h3>Background</h3><div>Few studies have discussed the effects and mechanism of dapagliflozin on diabetic kidney disease (DKD) with different glomerular filtration rate (GFR) and systolic blood pressure (SBP). This study aimed to investigate the variation in the eGFR and proteinuria after dapagliflozin treatment in DKD patients with different filtration status and SBP levels.</div></div><div><h3>Methods</h3><div>First, we conducted a cross-sectional study to determined hyperfiltration threshold for the DKD trial. Then, we enrolled 259 DKD patients with an eGFR greater than 70 mL/min/1.73m² and an albumin-to-creatinine ratio (ACR) between 30 and 200 mg/g to receive treatment with dapagliflozin. Hyperfiltration was defined as the 95th percentile of eGFR above the age- and gender- specific in healthy subjects, DKD patients were divided into hyperfiltration and non-hyperfiltration groups, and SBP &gt; 120 mmHg and ≤ 120 mmHg groups. The eGFR, ACR, and blood and urine electrolytes were measured before and after treatment.</div></div><div><h3>Results</h3><div>The mean eGFR change at 2 weeks in the hyperfiltration with SBP &gt; 120 mmHg group was greater than in the non-hyperfiltration with SBP ≤ 120 mmHg group (<em>P</em> = 0.048). The mean ACR reduction values were greater in the non-hyperfiltration with SBP ≤ 120 mmHg group than in the hyperfiltration with SBP &gt; 120 mmHg group at 12 weeks (<em>P</em> = 0.042). There was no difference in other blood or urine electrolytes before and after treatment, except for the fractional excretion of sodium (FENa), which significantly increased after 2 weeks (<em>P</em> &lt; 0.001) and recovered after 8 weeks (<em>P</em> = 0.305).</div></div><div><h3>Conclusion</h3><div>DKD with non-hyperfiltration with SBP ≤ 120 mmHg had a lower mean eGFR decline and greater decrease in the ACR after treatment. The initial increase in FENa and subsequent decrease after dapagliflozin treatment may be the main mechanism behind the eGFR variation.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107045"},"PeriodicalIF":4.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9 based knockout of lncRNA MALAT1 attenuates TGF-β1 induced Smad 2/3 mediated fibrosis during AKI-to-CKD transition","authors":"Bhupendra Puri ,&nbsp;Syamantak Majumder ,&nbsp;Anil Bhanudas Gaikwad","doi":"10.1016/j.ejps.2025.107044","DOIUrl":"10.1016/j.ejps.2025.107044","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a significant clinical issue with potential long-term consequences, as even a single episode can progress to chronic kidney disease (CKD). The AKI-to-CKD transition involves complex pathophysiology, including persistent inflammation, apoptosis, and fibrosis. Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recognized as a potential therapeutic target for various kidney diseases, including AKI and CKD. In our previous study, we conducted the transcriptomic analysis of lncRNAs <em>in-vitro</em> and animal models of AKI-to-CKD transition and found several dysregulated lncRNAs such as MALAT1, MEG3, NEAT1, MIAT, and H19 in this transition. Among these, we have selected lncRNA MALAT1 to further validate its role in AKI-to-CKD transition as a therapeutic target via a cluster regularly intercept short palindromic protein (CRISPR) associated protein 9 (Cas9)-mediated knockout approach in NRK52E cells. Guide RNAs (gRNAs) were designed to target MALAT1, and the PX459 turbo green fluorescence protein (GFP) plasmid containing MALAT1 gRNA1&amp;2 was transfected into NRK52E cells using CRISPRMAX. Results demonstrated that MALAT1 knockout significantly reduced MALAT1 expression and attenuated Smad2/3-mediated fibrosis by decreasing pSmad2, pSmad2/3, Smad4, vimentin, fibronectin, collagen-I, and α-SMA expression levels, while increasing Smad7, Smurf2, and E-cadherin levels. These findings suggest that targeting the MALAT1/Smad2/3 pathway could be a potential therapeutic target for mitigating fibrosis to prevent AKI-to-CKD transition.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107044"},"PeriodicalIF":4.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of the in vitro anti-leukemic effect of the histone deacetylase inhibitor romidepsin using Poly-(D, L-lactide-co-glycolide) nanoparticles as a drug carrier","authors":"Pinyadapat Aroonthongsawat ,&nbsp;Siriphan Manocheewa ,&nbsp;Chatchawan Srisawat ,&nbsp;Primana Punnakitikashem ,&nbsp;Yaneenart Suwanwong","doi":"10.1016/j.ejps.2025.107043","DOIUrl":"10.1016/j.ejps.2025.107043","url":null,"abstract":"<div><div>The goal of this work is to develop a delivery system for histone deacetylase inhibitor (HDACi) romidepsin (ROM) using Poly(D, L-lactide-co-glycolide) as a carrier and evaluate its anti-leukemic effects. Romidepsin-loaded nanoparticles (ROM NPs) required for this purpose were fabricated using a single emulsion-solvent evaporation technique. Their physical characteristics and <em>in vitro</em> drug release profiles were studied, alongside biocompatibility and hemocompatibility assessments. Cell viability assays and Annexin V/Propidium Iodide (PI) staining were conducted to evaluate the anti-leukemic and apoptosis induction efficiency of ROM NPs <em>in vitro</em>. ROM NPs displayed a spherical shape with an average hydrodynamic size of about 149.7 ± 8.4 nm, a PDI of 0.11 ± 0.03, and a zeta potential of -25.27 ± 2.12 mV. The nanoparticles demonstrated a high encapsulation efficiency of ROM (∼93 %) and these nanoparticles effectively entered acute leukemia cells, including U937 and Jurkat. ROM NPs also exhibited a prolonged biphasic release pattern, specifically, the initial burst release phase occurred within the first 24 h, followed by a slower, sustained release. Additionally, they showed no hematological or biological toxicity, indicating their potential use for the delivery of anti-cancer drugs through the circulatory system. In tests on acute leukemia cell lines, ROM NPs showed significantly stronger anti-leukemic effects and induced apoptosis to a greater extent compared to free ROM. In summary, ROM NPs represent a promising therapy option for leukemia according to their enhanced anti-leukemic effects. Further modification of this strategy could be performed to enable target specificity, hence minimizing damage to normal cells.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107043"},"PeriodicalIF":4.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical quality of herbal medicinal products and dietary supplements – a case study with oral solid formulations containing Lavandula species","authors":"Banaz Jalil ,&nbsp;Michael Heinrich","doi":"10.1016/j.ejps.2025.107042","DOIUrl":"10.1016/j.ejps.2025.107042","url":null,"abstract":"<div><div>The effectiveness and safety of regulated herbal medicinal products and dietary/food supplements are key areas of research. However, limited evidence exists of their pharmaceutical performance quality (including the standard in the respective pharmacopeial monographs). We evaluated the applicability of the European Pharmacopoeia general chapter protocols for disintegration testing of oral dosage forms using 73 products containing <em>Lavandula</em> species. Several <em>Lavandula</em> species, hybrids and cultivars are important medicinal plants globally in the phytopharmaceuticals and dietary/food supplement industry, including <em>Lavandula</em> Mill., traditionally used to treat conditions linked to nervousness and sleep disorders. We evaluate the pharmaceutical performance quality, particularly the <em>in vitro</em> disintegration and the phytochemical quality of 73 <em>Lavandula</em> oral dosage forms of single and multi–ingredients with different regulatory statuses. The phytochemical quality testing showed that 63 % of products contain less or none of the main marker compounds (e.g., linalool, linalyl acetate, and cineole). There was also considerable variability of the main marker compounds between products, with some containing ‘often/sometimes undeclared’ and significant amounts of rapeseed and sunflower oils as excipients. The pharmaceutical performance quality testing showed that 30 % of oral solid formulations always failed the disintegration testing (seven soft gels, ten hard shells, and five tablets/caplets). Pass rates for gelatine-based capsules were higher than for non-gelatine (cellulose-based) capsules. Overall, our findings highlighted problems with the pharmaceutical performance and phytochemical quality of the investigated products. These results have implications for the interpretations of the benefits and risks of phytopharmaceuticals used as compared to dietary/food supplements.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107042"},"PeriodicalIF":4.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of surface energy and surface tension on vial fogging within lyophilized drug products","authors":"Shuangxiu Shu ,&nbsp;Zidan Yuan ,&nbsp;Jitang Chen ,&nbsp;Zhi Yang ,&nbsp;Lingyun Zou ,&nbsp;Yuhui Gong ,&nbsp;Chunyuan Jia ,&nbsp;Bingquan (Stuart) Wang ,&nbsp;Jianjun Luo","doi":"10.1016/j.ejps.2025.107040","DOIUrl":"10.1016/j.ejps.2025.107040","url":null,"abstract":"<div><div>Vial fogging is a typical cosmetic cake appearance issue in lyophilized products, mostly occurring in amphiphilic protein-like freeze-dried formulations, especially antibody drug conjugate (ADC) formulations. Although fogging is currently believed to have no directly impact on product quality, its occurrence can raise concerns about container closure integrity, leading to an increased product rejection rate in pharmaceutical production. Vial fogging is typically believed to be related to the driving force from the interfacial energy at the liquid/solid interface, which is impacted by several factors. This study delves into fogging impacting factors including vial types, depyrogenation process, and formulation with the aim of appearance enhancement. Employing a Surface Tensiometer and a Drop Shape Analyzer to ascertain surface tension, surface energy, and contact angle measurements, this study incorporated results from lyophilization processes as well and discerned that the degree of fogging is directly proportional to the increase in surface energy and inversely related to surface tension. Consequently, this research identified the critical parameters for forecasting the fogging level prior to lyophilization, offering innovative strategies for enhancing the visual quality of lyophilized pharmaceuticals in subsequent developments.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107040"},"PeriodicalIF":4.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular fungal Hsp90 represents a promising therapeutic target for combating fungal infections","authors":"Ting Fang,&nbsp;Hui Lu (Associate Senior Research Fellow),&nbsp;Yuanying Jiang (Professor)","doi":"10.1016/j.ejps.2025.107041","DOIUrl":"10.1016/j.ejps.2025.107041","url":null,"abstract":"<div><div>Heat shock protein 90 (Hsp90) is a pivotal virulence factor in pathogenic fungi, playing a significant role in conferring drug resistance. However, due to the high amino acid sequence similarity between fungal and mammalian Hsp90, targeting fungal intracellular Hsp90 therapeutically is associated with marked toxic side effects, thereby limiting clinical application. Studies have demonstrated that intracellular fungal Hsp90 can be secreted as extracellular Hsp90 (eHsp90), which plays a crucial role in fungal infections. Strategies targeting fungal eHsp90 have exhibited promising therapeutic outcomes. Unlike intracellular targeting, such antifungal approaches can operate without cell penetration, thereby circumventing the toxic side effects due to Hsp90′s high conservation. This review summarizes the potential extracellular secretion pathways of fungal eHsp90, its roles in fungal pathogenesis, as well as the development of vaccines and antibodies targeting fungal eHsp90. The review underlines the significance of eHsp90 in fungal infections and suggests that eHsp90 represents a promising therapeutic target for fungal infection treatment.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"207 ","pages":"Article 107041"},"PeriodicalIF":4.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}