European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Functionalisation of chitosan with methacryloyl and crotonoyl groups as a strategy to enhance its mucoadhesive properties","authors":"Shiva Vanukuru ,&nbsp;Fraser Steele ,&nbsp;Natalia N. Porfiryeva ,&nbsp;Alejandro Sosnik ,&nbsp;Vitaliy V. Khutoryanskiy","doi":"10.1016/j.ejpb.2024.114575","DOIUrl":"10.1016/j.ejpb.2024.114575","url":null,"abstract":"<div><div>Mucoadhesive polymers are crucial for prolonging drug retention on mucosal surfaces. This study focuses on synthesising and characterising novel derivatives by reacting chitosan with crotonic and methacrylic anhydrides. The structure of the resulting derivatives was confirmed using proton-nuclear magnetic resonance spectroscopy and Fourier-transform infrared spectroscopy. It was established that the degree of substitution plays a crucial role in the pH-dependent solubility profiles and electrophoretic mobility of the chitosan derivatives. Spray-drying chitosan solutions enabled preparation of microparticles, whose mucoadhesive properties were evaluated using fluorescence flow-through studies and tensile test, demonstrating improved retention on sheep nasal mucosa for modified derivatives. Acute toxicity studies conducted <em>in vivo</em> using planaria and <em>in vitro</em> using MTT assay with the Caco-2 cell line, a model of the mucosal epithelium <em>in vitro</em>, showed that the novel derivatives are not cytotoxic. These findings emphasise the potential of tailored chitosan chemical modifications for enhancing transmucosal drug delivery.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114575"},"PeriodicalIF":4.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603737","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":"Transitioning from Pickering emulsions to Pickering emulsion hydrogels: A potential advancement in cosmeceuticals","authors":"Akashni Rajoo ,&nbsp;Sangeetaprivya P. Siva ,&nbsp;Chin Siew Sia ,&nbsp;Eng-Seng Chan ,&nbsp;Beng Ti Tey ,&nbsp;Liang Ee Low","doi":"10.1016/j.ejpb.2024.114572","DOIUrl":"10.1016/j.ejpb.2024.114572","url":null,"abstract":"<div><div>Cosmeceuticals, focusing on enhancing skin health and appearance, heavily rely on emulsions as one of the common mediums. These emulsions pose a challenge due to their dependence on surfactants which are essential for stability but are causing concerns about environmental impact as well as evolving consumer preferences. This has led to research focused on Pickering emulsions (PEs), which are colloidal particle-based emulsion alternatives. Compared to conventional emulsions, PEs offer enhanced stability and functionality in addition to serving as a sustainable alternative but still pose challenges such as rheological control and requiring further improvement in long-term stability, whereby the limitations could be addressed through the introduction of a hydrogel network. In this review, we first highlight the strategies and considerations to optimize active ingredient (AI) absorption and penetration in a PE-based formulation. We then delve into a comprehensive overview of the potential of Pickering-based cosmeceutical emulsions including their attractive features, the various Pickering particles that can be employed, past studies and their limitations. Further, PE hydrogels (PEHs), which combines the features between PE and hydrogel as an innovative solution to address challenges posed by both conventional emulsions and PEs in the cosmeceutical industry is explored. Moreover, concerns related to toxicity and biocompatibility are critically examined, alongside considerations of scalability and commercial viability, providing a forward-looking perspective on potential future research directions centered on the application of PEHs in the cosmeceutical field.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114572"},"PeriodicalIF":4.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564135","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":"Computational and experimental analysis of Luteolin-β-cyclodextrin supramolecular complexes: Insights into conformational dynamics and phase solubility","authors":"Pramod Kumar ,&nbsp;Vijay Kumar Bhardwaj ,&nbsp;Pravin Shende ,&nbsp;Rituraj Purohit","doi":"10.1016/j.ejpb.2024.114569","DOIUrl":"10.1016/j.ejpb.2024.114569","url":null,"abstract":"<div><div>Investigating the structural stability of poorly-soluble luteolin (LuT) after encapsulation within cyclodextrins (CDs) is crucial for unlocking the therapeutic potential of LuT bioactive molecule. Herein, native and modified β-CD were employed to investigate LuT inclusion complex formation. Molecular mechanics (MM) and quantum mechanics (QM) were utilized for structural dynamics analysis. Microsecond timescale MD simulations yielded insights into LuT-CD interactions. The binding affinity between LuT and selected β-CDs was assessed by calculating the binding free energy using MM-PBSA and umbrella sampling simulations. The MM-PBSA results indicated that Heptakis-O-(2-hydroxypropyl)-β-CD (HP-β-CD) (−82.59+/-11.67 kJ/mol) and Di-O-methyl-β-CD (DM-β-CD) (−54.01+/-11.07 kJ/mol) exhibited good binding affinity for LuT. Subsequently, derivative screening of HP-β-CD revealed that only 2-HP-β-CD (HP-β-CD-1)/LuT (−21.38 kJ/mol) displayed a superior binding free energy (obtained from umbrella sampling) than HP-β-CD/LuT (−16.55 kJ/mol) inclusion complex. We conducted QM calculations on the top three inclusion complexes namelly HP-β-CD, DM-β-CD, and HP-β-CD-1 employing wB97X-D/6–311 + G(d,p) model chemistry to strengthen the MM results. The computational analysis aligns with experimental findings (phase solubility analysis), validating HP-β-CD-1 as most effective cavitand molecule for improving the solubility of LuT. This study offers critical structural insights for developing novel HP-β-CD derivatives with enhanced host capacity to encapsulate guest molecules efficiently.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114569"},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557408","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":"Electrospun nanofibers for localized drug release of a neuroprotective natural extract of Usnea ghattensis","authors":"María de la Cabeza Fernández ,&nbsp;Marta Sánchez ,&nbsp;Laura Lozano-Chamizo ,&nbsp;Ana Cristina Abreu ,&nbsp;Ana Anguís-Morillas ,&nbsp;Padreep K Divakar ,&nbsp;Marzia Marciello ,&nbsp;Marco Filice ,&nbsp;Victor Gonzalez-Rumayor ,&nbsp;Ignacio Fernández ,&nbsp;Rafael Contreras-Cáceres ,&nbsp;Pilar Gómez-Serranillos","doi":"10.1016/j.ejpb.2024.114552","DOIUrl":"10.1016/j.ejpb.2024.114552","url":null,"abstract":"<div><div>This research is based on the incorporation of the methanolic extract of the <em>Usnea ghattensis</em> into poly (caprolactone) (PCL) nanofibers (NFs) to investigate the capacity in reducing reactive oxygen species (ROS). PCL-NFs were fabricated by the electrospinning technique and are investigated as potential dressing material focused on the release of usnic acid (PCL-USNIC NFs), and its encapsulation efficiency and kinetic release were analyzed by high performance liquid chromatography (HPLC). This investigation was performed by analyzing the usnic acid concentration as a function of the distance from the mat center point. The kinetic release analysis is also developed with the <em>usnea ghattensis</em> extract (PCL-USNEA NFs), performing a metabolomic analysis of the released molecules as a function of time by nuclear magnetic resonance (NMR). Usnic acid was revealed as the most relevant compound together with other molecules, such as sucrose, mannitol, arabitol or glycerol that generate a positive matrix effect on the release of usnic acid. Finally, we analize the cytotoxicity and the neuroprotective effect of PCL-USNEA and PCL-USNIC NFs using a human neuroblastoma cell line model. Negligible toxicity was appreciated for both polymeric systems, showing high protective effects in presence of highly oxidative environment (e.g. in presence of H₂O₂).</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114552"},"PeriodicalIF":4.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544581","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":"Enhancing RNA encapsulation quantification in lipid nanoparticles: Sustainable alternatives to Triton X-100 in the RiboGreen assay","authors":"David Schultz ,&nbsp;Rasmus D. Münter ,&nbsp;Alex M. Cantín ,&nbsp;Paul J. Kempen ,&nbsp;Nadin Jahnke ,&nbsp;Thomas L. Andresen ,&nbsp;Jens B. Simonsen ,&nbsp;Andrew J. Urquhart","doi":"10.1016/j.ejpb.2024.114571","DOIUrl":"10.1016/j.ejpb.2024.114571","url":null,"abstract":"<div><div>To quantify concentration and encapsulation efficiency (EE) of mRNA in lipid nanoparticles (LNPs) the RiboGreen assay is extensively used. As part of this assay, a surfactant is used to release mRNA from LNPs for detection with the RiboGreen dye. So far, the surfactant of choice has been Triton X-100, which is harmful to human health and the environment. Alternatives to Triton X-100 are therefore needed, but surprisingly no such effort has yet been described in the literature. Here we show how three, less harmful, surfactants (Brij 93, Zwittergent 3–14 and Tween 20) compare to Triton X-100 for releasing mRNA from LNPs for detection with the RiboGreen assay. We found that Zwittergent 3–14 and Tween 20 at high concentrations (0.5 %) are at the minimum as effective as Triton X-100 at high concentration (0.5 %) across three different mRNA-LNP formulations. Interestingly, Tween 20 was the most effective at releasing mRNA from LNPs, across all concentration ranges explored (0.0025 %, 0.01 %, 0.1 % and to 0.5 % (v/v)) highlighting its potency at solubilizing the three different LNP formulations. Our results show that Tween 20 can be used as an alternative to Triton X-100 in the RiboGreen assay, resulting in more accurate quantification of the total mRNA concentration and EE%, as well as making the assay more environmentally friendly. Such improvement could potentially increase the likelihood of identifying therapeutically attractive hard-to-solubilize LNP-mRNA formulations that would be discharged when using Triton X-100 due to their apparent low EE values, as well as ensure more accurate mRNA dosing in both in vitro and in vivo studies.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114571"},"PeriodicalIF":4.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568161","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":"Accelerating thrombolysis of arterial thrombus with NO-MBs UTMD therapy","authors":"Binbin Shi ,&nbsp;Qiaohua Yang ,&nbsp;Zenghui Liang ,&nbsp;Runjie Yu ,&nbsp;Hui Li ,&nbsp;Qilong Wu ,&nbsp;Mingling Fang ,&nbsp;Lili Lin ,&nbsp;Huafang Chen ,&nbsp;Yingzheng Zhao ,&nbsp;Bin Chen","doi":"10.1016/j.ejpb.2024.114566","DOIUrl":"10.1016/j.ejpb.2024.114566","url":null,"abstract":"<div><div>Arterial thrombotic disease is a common and serious clinical medical problem. Nitric oxide (NO), as a therapeutic gas, can delay the progression of thrombosis and reduce tissue ischemia and hypoxia damage. However, systemic delivery of NO causes complications, and NO in the body is easily cleared by hemoglobin in the blood. In this study, we designed a lipid microbubble carrying NO (NO-MBs) combined with ultrasound-targeted microbubble destruction (UTMD) technology to achieve targeted delivery of NO under real-time contrast-enhanced ultrasound monitoring. The good stability of the NO-MBs was demonstrated by examining the changes in diameter, concentration and contrast-enhanced ultrasound intensity with time. Moreover, in vivo and in vitro thrombolysis experiments, it was confirmed that the combination of NO-MBs and UTMD could accelerate arterial thrombolysis. Meanwhile, the levels of inflammatory factors, superoxide dismutase (SOD) and malondialdehyde (MDA) in vascular tissue after treatment were detected, which showed that NO-MBs could significantly reduce the inflammatory response and oxidative stress induced by thromboembolism. In addition, so as to‌ evaluate the safety of the NO-MBs UTMD treatment strategy, MTT assay, hemolysis test, detection of serum biochemical indicators, and H&amp;E staining of major organs were performed. The results showed that this treatment strategy had excellent biosafety. In conclusion, the NO-MBs UTMD treatment strategy has great potential in the treatment of arterial thrombotic diseases.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114566"},"PeriodicalIF":4.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544579","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":"Deep eutectic solvent combined with permeation enhancer strategy to convert tandospirone from oral to transdermal formulations improving drug bioavailability","authors":"Peng Sun,&nbsp;Hui Li,&nbsp;Kaihua Gong,&nbsp;Yang Zhang,&nbsp;Yu Cai,&nbsp;Chao Liu,&nbsp;Liang Fang","doi":"10.1016/j.ejpb.2024.114570","DOIUrl":"10.1016/j.ejpb.2024.114570","url":null,"abstract":"<div><div>Tandospirone(Tan) is a commonly used drug for anxiety treatment. However, it has a significant first-pass effect and needs to be taken three times a day. To increase the bioavailability of the drug and reduce the number of administrations, this work amid to prepare a Tan patch that can be administered once a day by using the strategy of therapeutic deep eutectic solvent(THEDES) in cooperation with chemical permeation enhancer(CPE). In this study, four organic acids and five permeation enhancers were selected, and the optimized formulation was obtained by single-factor investigation and Box-Behnken design. The optimized formulation could significantly enhance drug loading by 2.5-fold and skin permeation up to 586.6 ± 17 μg/cm² in rats. Based on pharmacokinetic results, compared to oral administration, the drug exhibited a substantially elevated bioavailability, registering a 17-fold increase(from 3.01 % to 52.17 %), alongside a 10-fold rise in the mean residence time(MRT). Meanwhile, the patch was not irritating. The results of the mechanistic study showed that levulinic acid(LeA) acted as a bridge to increase the interaction between the Tan and the matrix and inhibited the crystallization of the drug in the patch, and THEDES together with CPE improved the matrix fluidity and skin permeability. This study provides a reference for the joint application of THEDES and CPEs in patch development.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114570"},"PeriodicalIF":4.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554301","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":"Machine learning driven bioequivalence risk assessment at an early stage of generic drug development","authors":"Dejan Krajcar ,&nbsp;Dejan Velušček ,&nbsp;Iztok Grabnar","doi":"10.1016/j.ejpb.2024.114553","DOIUrl":"10.1016/j.ejpb.2024.114553","url":null,"abstract":"<div><h3>Background</h3><div>Bioequivalence risk assessment as an extension of quality risk management lacks examples of quantitative approaches to risk assessment at an early stage of generic drug development. The aim of our study was to develop a model-based approach for bioequivalence risk assessment that uses pharmacokinetic and physicochemical characteristics of drugs as predictors and would standardize the first step of risk assessment.</div></div><div><h3>Methods</h3><div>The Sandoz in-house bioequivalence database of 128 bioequivalence studies with poorly soluble drugs (23.5% non-bioequivalent) was used to train and validate the model. Four different modeling approaches, random forest, XGBoost, logistic regression and naïve Bayes, were compared.</div></div><div><h3>Results</h3><div>Among the best performing machine learning models, random forest was selected and optimized for the number of features, resulting in an accuracy of 84% on the test data set. The most important features for prediction were those related to solubility (dose number, acid dissociation constant), absorption and elimination rate, effective permeability, variability of pharmacokinetic endpoints, and absolute bioavailability. All features had a conceivable influence on the model predictions.</div></div><div><h3>Conclusion</h3><div>The model was used to develop a bioequivalence risk assessment approach to categorize drugs in early development into high, medium or low risk classes.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114553"},"PeriodicalIF":4.4,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560962","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":"Evaluation of a mucoadhesive auto-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration","authors":"M.O.F. Muñoz-Correa ,&nbsp;Diego A. Bravo-Alfaro ,&nbsp;L.G. Mendoza-Sánchez ,&nbsp;Gabriel Luna-Barcenas ,&nbsp;Hugo S. Garcia ,&nbsp;Rebeca Garcia-Varela","doi":"10.1016/j.ejpb.2024.114567","DOIUrl":"10.1016/j.ejpb.2024.114567","url":null,"abstract":"<div><div>This study investigated the potential of self-nanoemulsifying drug delivery systems (SNEDDS) to optimize the oral bioavailability of insulin. Insulin complexes with phospholipids and enzymatically-modified phospholipids were developed and incorporated into the SNEDDS using Lauroglycol FCC as the oily phase and Cremophor EL and Labrafil M1944CS as the surfactant and co-surfactant, respectively. Additionally, mucoadhesive polysaccharides (sodium alginate and guar gum) were added further to enhance the bioavailability of insulin in these systems. The objective was to increase the bioavailability and bioactivity of an insulin-modified phosphatidylcholine complex by incorporating mucoadhesives into the SNEDDS. After polymer inclusion, the resulting nanoemulsions exhibited droplet diameters ranging from 57 to 83 nm. Cytotoxicity and apparent permeability tests were conducted on Caco-2 and NIH 3 T3 cell lines, revealing that toxicity was related to the concentrations of insulin and surfactant in the nanosystems—formulations containing guar gum as a mucoadhesive showed better tolerance to cell death in the Caco-2 line. In a murine diabetes model, the SNEDDS were observed to reduce glucose levels by up to 61.63 %, with a relative bioavailability of 2.25 % compared to subcutaneously administered insulin. These results suggest that SNEDDS incorporating mucoadhesives could represent a promising strategy for improving oral insulin delivery.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114567"},"PeriodicalIF":4.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring yeast glucans for vaccine enhancement: Sustainable strategies for overcoming adjuvant challenges in a SARS-CoV-2 model","authors":"João Azevedo-Silva ,&nbsp;Manuela Amorim ,&nbsp;Diana Tavares-Valente ,&nbsp;Pedro Sousa ,&nbsp;Raodoh Mohamath ,&nbsp;Emily A. Voigt ,&nbsp;Jeffrey A. Guderian ,&nbsp;Robert Kinsey ,&nbsp;Sofia Viana ,&nbsp;Flávio Reis ,&nbsp;Manuela E. Pintado ,&nbsp;Christopher J. Paddon ,&nbsp;Christopher B. Fox ,&nbsp;João C. Fernandes","doi":"10.1016/j.ejpb.2024.114538","DOIUrl":"10.1016/j.ejpb.2024.114538","url":null,"abstract":"<div><div>Vaccine adjuvants are important for enhancing vaccine efficacy, and although aluminium salts (Alum) are the most used, their limited ability to induce specific immune responses has spurred the search for new adjuvants. However, many adjuvants fail during product development due to manufacturability, supply, stability, or safety concerns. This work hypothesizes that protein-free yeast glucans can be used as vaccine adjuvants due to their known immunostimulatory activity and high abundancy. Thus, high molecular weight glucans with over 99% purity, comprising 64–70% β-glucans and 29–35% α-glucans, were extracted from a wild-type yeast and an engineered yeast to produce a steviol glycoside. These glucans underwent carboxymethylation to enhance solubility. Both water-dispersible and particulate glucans were evaluated as adjuvants, either alone or in combination with Alum or squalene stable emulsion (SE), for a SARS-CoV-2 vaccine. The study demonstrated that glucans triggered a robust immune response and enhanced the effects of Alum and SE when used in combination, both <em>in vitro</em> and <em>in vivo</em>. Water-dispersible glucans combined with Alum, and particulate glucans combined with SE, increased the production of specific antibodies against SARS-CoV-2 spike protein and enhanced serum neutralization titers against SARS-CoV-2 pseudovirus. Furthermore, the results indicated that larger molecular weight glucans from engineered yeast exhibited stronger immunogenic activity in comparison to wild-type yeast glucans. In conclusion, appropriately formulated glucans have the potential to be scalable, low-cost vaccine adjuvants, potentially overcoming the limitations of current adjuvants.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"205 ","pages":"Article 114538"},"PeriodicalIF":4.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497548","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}