Molecular Pharmaceutics最新文献

{"title":"BODIPY-Based Photothermal Agent Incorporating Azulene for Enhanced NIR Absorption and Tumor Ablation.","authors":"Kai Nishimura, Mikiya Kato, Tomoya Fukui, Kazuki Miura, Masato Tsuda, Satoshi Okada, Takanori Fukushima, Hiroyuki Nakamura","doi":"10.1021/acs.molpharmaceut.5c00071","DOIUrl":"10.1021/acs.molpharmaceut.5c00071","url":null,"abstract":"<p><p>Photothermal therapy (PTT) is a promising minimally invasive treatment that converts light energy into localized heat for tumor ablation. Indocyanine green (ICG), the only clinically approved photothermal agent (PTA), suffers from rapid photobleaching and poor tumor retention, underscoring the urgent need for next-generation PTAs with improved properties. In this study, we report AzuGlu-BODIPY, a novel azulene-containing BODIPY-based PTA incorporating 1,2,3,4-tetrahydroquinoline and glucose, designed to overcome these limitations. AzuGlu-BODIPY demonstrates a high photothermal conversion efficiency (PCE) of 51%, effective near-infrared (NIR) absorption, and thermal stability in both dimethyl sulfoxide (DMSO) and aqueous solutions. <i>In vitro</i> studies revealed potent photothermal efficacy against cancer cell lines, with IC₅₀ values of 3.1-4.6 μM under 808 nm laser irradiation, while <i>in vivo</i> experiments showed complete tumor regression in 4T1 tumor-bearing mice following localized administration and laser treatment. These results suggest AzuGlu-BODIPY as a promising PTA and provide a versatile platform for advancing azulene-based PTAs with enhanced functionality for PTT.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2660-2670"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750279","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":"Correlation between Olfaction and Cognition Using PET Quantification of Alzheimer's Disease Biomarkers in Intracranial Olfactory-Related Regions of 3xTg Mice.","authors":"Yulin Wang, Wanchen Liao, Kaiyu Ye, Yuqi Wang, Jun Li, Dongqing Huang, Xinyang Hong, Weibin Cheng, Ping Luan, Junzhang Tian","doi":"10.1021/acs.molpharmaceut.4c01532","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01532","url":null,"abstract":"<p><p>Olfactory impairment is a preclinical symptom of Alzheimer's disease (AD); however, the mechanism of olfactory dysfunction in AD is not clear. This study aims to explore the mechanism of olfactory dysfunction in AD by analyzing the correlation between olfaction and cognition using positron emission tomography (PET) quantification of biomarkers, including amyloid β (Aβ) and abnormal tau proteins in the intracranial olfactory-related regions of AD model mice, and compares PET quantification with pathological detection to explore the reliability of the transformation of PET into clinical research. A total of 14 mice, including 3xTg mice (12 months old, <i>n</i> = 7) and wild-type (WT) mice (12 months old, <i>n</i> = 7), were enrolled in the study. Behavioral experiments (olfactory: buried food test, cognitive: Morris water maze) were performed to assess whether the mice had abnormal olfactory and cognitive functions. PET quantified Aβ and abnormal tau in olfactory-related regions. The expression and distribution of Aβ and phosphorylated tau were observed by immunofluorescence. Compared with WT mice, 3xTg mice had olfactory and cognitive impairments. Quantitative PET and immunofluorescence showed that 3xTg mice had significantly more Aβ and abnormal tau accumulation in olfactory areas than did WT mice. The deposition of Aβ and phosphorylated tau in olfactory-related regions of 3xTg mice suggests a potential link between olfactory pathology and AD progression. The elevated uptake of Aβ and tau PET in the olfactory-related regions further highlights the potential of olfactory-targeted molecular imaging as a noninvasive biomarker for AD detection.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 5","pages":"2603-2612"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955024","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":"Mechanistic Insights into the Antibiofilm Activity of Simvastatin and Lovastatin against <i>Bacillus subtilis</i>.","authors":"Nidhi Verma, Mamta Bajiya, Ragini Dolhey, Surabhi, Abhishek Singh Yadav, Chhavi Chaudhary, Dhankesh Meena, Hemant Arya, Tarun K Bhatt, Jay Kant Yadav, Jayendra Nath Shukla, Shiv Swaroop, Janmejay Pandey","doi":"10.1021/acs.molpharmaceut.5c00191","DOIUrl":"10.1021/acs.molpharmaceut.5c00191","url":null,"abstract":"<p><p>Statins have been reported for diverse pleiotropic activities, including antimicrobial and antibiofilm. However, due to the limited understanding of their mode of action, none of the statins have gained approval for antimicrobial or antibiofilm applications. In a recent drug repurposing study, we observed that two statins (<i>i.e</i>., Simvastatin and Lovastatin) interact stably with TasA_(28-261), the principal extracellular matrix protein of <i>Bacillus subtilis</i>, and also induce inhibition of biofilm formation. Nevertheless, the underlying mechanism remained elusive. In the present study, we examined the impact of these statins on the physiological activity of TasA_(28-261), specifically its interaction with TapA_(33-253) and aggregation into the amyloid-like structure using purified recombinant TasA_(28-261) and TapA_(33-253) in amyloid detection-specific <i>in vitro</i> assays (<i>i.e</i>., CR binding and ThT staining assays). Results revealed that both statins interfered with amyloid formation by the TasA_(28-261)-TapA_(33-253) complex, while neither statin inhibited amyloid formation by lysozyme, a model amyloid-forming protein. Moreover, neither statin significantly altered the expressions of terminal regulatory genes (<i>viz</i>, <i>sinR</i>, <i>sinI</i>) and terminal effector genes (<i>viz</i>, <i>tasA</i>, <i>tapA</i>, and <i>bslA</i>) involved in biofilm formation by <i>B. subtilis</i>. While the intricate interplay between Simvastatin and Lovastatin with the diverse molecular constituents of <i>B. subtilis</i> biofilm remains to be elucidated conclusively, the findings obtained during the present study suggest that the underlying mechanism for Simvastatin- and Lovastatin-mediated inhibition of <i>B. subtilis</i> biofilm formation is manifested by interfering with the aggregation and amyloid formation by TasA_(28-261)-TapA_(33-253). These results represent one of the first experimental evidence for the underlying mechanism of antibiofilm activity of statins and offer valuable directions for future research to harness statins as antibiofilm therapeutics.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2703-2722"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655524","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":"Beyond Correlation: Establishing Causality in Protein Corona Formation for Nanomedicine.","authors":"Arshia Rafieioskouei, Kenneth Rogale, Amir Ata Saei, Morteza Mahmoudi, Borzoo Bonakdarpour","doi":"10.1021/acs.molpharmaceut.5c00262","DOIUrl":"10.1021/acs.molpharmaceut.5c00262","url":null,"abstract":"<p><p>In contemporary studies on the role of the protein corona in specific biological applications, identifying <i>correlation</i> is widely used to draw conclusions from observations and statistical methods, yet it merely identifies associations without establishing a direct influence between variables. This over reliance on observation can lead to spurious connections where co-occurrence does not imply causation. In contrast, a <i>causality</i>-focused approach asserts the direct impact of one variable on another, offering a more robust framework for inference and the drawing of scientific conclusions. This approach allows researchers to better predict how changes in a nanoparticle's physicochemical properties or biological conditions will affect protein corona composition and decoration, in turn affecting their safety and therapeutic/diagnostic efficacies. As a proof of concept, we explore the concept of \"actual causality\" (introduced by Halpern and Pearl) to mathematically prove how spiking small molecules, including metabolites, lipids, vitamins, and nutrients, into plasma can induce diverse protein corona patterns on identical nanoparticles. This approach significantly enhances the depth of plasma proteome profiling. Our findings reveal that among the various spiked small molecules, phosphatidylcholine was the actual cause of the observed increase in the proteomic depth of the plasma sample. By considering the concept of causality in the field of protein coronas, the nanomedicine community can substantially improve the ability to design safer and more efficient nanoparticles for both diagnostic and therapeutic purposes.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2723-2730"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810098","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":"Structural Similarity of Biological Drugs Using Statistical Signal Processing and Nuclear Magnetic Resonance Spectral Pattern Analysis.","authors":"Soumya Ranjan Pujahari, Swpnil Engla, Rohit Soni, Subrata Patra, Manjesh Kumar Hanawal, Ashutosh Kumar","doi":"10.1021/acs.molpharmaceut.5c00108","DOIUrl":"10.1021/acs.molpharmaceut.5c00108","url":null,"abstract":"<p><p>Biosimilar drugs are highly similar to the available marketed drugs and have no clinically meaningful differences in terms of safety, purity, and potency. As per stringent drug regulatory requirements, biosimilar drugs must match closely to all attributes of the listed marketed drug, including establishing high similarity of higher-order structures. Here, we have developed a combined approach using high-resolution two-dimensional nuclear magnetic resonance (NMR) spectra and image-based statistical signal processing algorithms to establish robust comparability of critical quality attributes of biological drugs. We have integrated a computational approach to 2D NMR data analysis, which could replace the traditional methods of manually extracting chemical shift values and intensities for each peak and performing a range of statistical analyses, which are laborious and prone to ambiguity. Our algorithm simplifies and streamlines this process, making it more accurate, less time-consuming, and avoiding personal biases. We have employed our methods with a diverse range of biotherapeutics and complex NMR data and shown a degree of similarity between reference and test drugs with our differentially assigned similarity scores.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2684-2693"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810127","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":"Role of Microneedles for Improved Treatment of Obesity: Progress and Challenges.","authors":"Sudarshan Naidu Chilamakuri, Manasa N, Maharshi Thalla, Ravichandiran Velayutham, Youjin Lee, Sung Min Cho, Hyungil Jung, Subramanian Natesan","doi":"10.1021/acs.molpharmaceut.4c01115","DOIUrl":"10.1021/acs.molpharmaceut.4c01115","url":null,"abstract":"<p><p>Obesity is a global metabolic health epidemic characterized by excessive lipid and fat accumulation, leading to severe conditions such as diabetes, cancer, and cardiovascular disease. Immediate attention and management of obesity-related health risks are most warranted. The imbalance between fat absorption, metabolic rate, and environmental and genetic factors is responsible for obesity. Treatment typically involves lifestyle modifications, pharmacotherapy, and surgery. While lifestyle changes are crucial, effective treatment often necessitates medication as a preferred adjunct strategy. However, medications commonly used, such as oral pharmacotherapy, often show side effects due to systemic exposure and, thus, may not effectively target the intended areas, leading to drug loss. On the other hand, transdermal administration of drugs with microneedle (MN)-based technologies, a painless drug delivery approach with patient compliance, is gaining interest as an alternative obesity treatment, as it directly targets adipose tissue via local delivery, minimizing system exposure and dose reduction. This Review addresses the pathophysiology of obesity, current treatment strategies, challenges in the treatment of obesity using conventional formulations, the importance of the use of nano-based medications through transdermal delivery, and the use of MNs as a promising platform for the effective delivery of nanoparticle-based anti-obesity medications. The potential of combining MNs with stimuli-responsive and non-responsive adjuvant therapies to enhance treatment efficacy and patient outcomes is explored. In addition, the limitations and future perspectives related to the use of MNs for obesity are addressed to highlight the transformative potential of this technology for obesity management. MNs hold promise in precisely delivering anti-obesity drugs while requiring lower dosages and minimizing side effects compared to conventional oral or injectable therapies and ultimately improving the quality of life for individuals struggling with obesity and its associated comorbidities.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2350-2371"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750285","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":"Nanotherapeutic Formulations for the Delivery of Cancer Antiangiogenics.","authors":"Amelia Ultimo, Ayushi Jain, Elisabet Gomez-Gonzalez, Thomson Santosh Alex, Almudena Moreno-Borrallo, Sukanya Jana, Shubhrima Ghosh, Eduardo Ruiz-Hernandez","doi":"10.1021/acs.molpharmaceut.4c00822","DOIUrl":"10.1021/acs.molpharmaceut.4c00822","url":null,"abstract":"<p><p>Antiangiogenic medications for cancer treatment have generally failed in showing substantial benefits in terms of prolonging life on their own; their effects are noticeable only when combined with chemotherapy. Moreover, treatments based on prolonged antiangiogenics administration have demonstrated to be ineffective in stopping tumor progression. In this scenario, nanotherapeutics can address certain issues linked to existing antiangiogenic treatments. More specifically, they can provide the ability to target the tumor's blood vessels to enhance drug accumulation and manage release, ultimately decreasing undesired side effects. Additionally, they enable the administration of multiple angiogenesis inhibitors at the same time as chemotherapy. Key reports in this field include the design of polymeric nanoparticles, inorganic nanoparticles, vesicles, and hydrogels for loading antiangiogenic substances like endostatin and interleukin-12. Furthermore, nanoformulations have been proposed to efficiently control relevant pro-angiogenic pathways such as VEGF, Tie2/Angiopoietin-1, HIF-1α/HIF-2α, and TGF-β, providing powerful approaches to block tumor growth and metastasis. In this article, we outline a selection of nanoformulations for antiangiogenic treatments for cancer that have been developed in the past ten years.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2322-2349"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784376","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":"Pilot Study of Intratumoral Immunotherapy with Cowpea Mosaic Virus Nanoparticles: Safety in Refractory Canine Oral Tumors.","authors":"Pablo Delgado-Bonet, Hugo Arias-Pulido, Noemí Del Castillo Magan, Anna Barbara Emilia Zimmermann, Evelien Schaafsma, Johannes Vom Berg, Fernando Vázquez, Veronique Beiss, Nicole F Steinmetz, Steven Fiering, Ana Judith Perisé-Barrios","doi":"10.1021/acs.molpharmaceut.5c00100","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00100","url":null,"abstract":"<p><p>Oral tumors (squamous cell carcinoma, malignant melanoma, and fibrosarcoma) represent 6-7% of all canine cancers. Given that these tumors have a high local recurrence rate and metastatic potential, conventional therapies have suboptimal response rates, leading to poor patient outcomes. Here, we report the use of intratumoral virus-like particles from cowpea mosaic virus (CPMV) in four canine patients with recurrent oral malignant tumors and lymph node metastasis. All tumors were nonresponders to chemotherapy and had a mild initial response to CPMV intratumoral immunotherapy without any serious immune-related adverse effects. None of the patients developed pulmonary metastasis during follow-up, although local progression was seen in all the patients. Furthermore, tumor-infiltrated immune T cells increased in number after the intratumoral immunotherapy with CPMV, suggesting activation of the tumor microenvironment. All the patients had a rapid decrease in the tumor-promoting chemokines IL-8 and CXCL1, which could indicate that a decrease in metastatic potential could have been generated by the CPMV immunotherapy. The increased number of infiltrated immune cells, the decrease in some pro-tumoral chemokines, and the absence of adverse effects suggest that CPMV could be a safe treatment and should be further explored as a novel therapy for canine oral tumors.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 5","pages":"2671-2683"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955029","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":"Nanoparticle Albumin-Bound Bortezomib: Enhanced Antitumor Efficacy and Tumor Accumulation in Breast Cancer Therapy.","authors":"Anita Saremi Poor, Bagher Davaeil, Marziyeh Ramezanpour, Mehdi Shafiee Ardestani, Ali Akbar Moosavi-Movahedi, S Mohsen Asghari","doi":"10.1021/acs.molpharmaceut.4c01283","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01283","url":null,"abstract":"<p><p>Nanoparticle albumin-bound (NAB) formulations are emerging as a viable strategy for the intravenous delivery of poorly water-soluble drugs. This study aims to improve the therapeutic profile of Bortezomib (BTZ), addressing its low solubility and significant systemic toxicity through the development of NAB-BTZ nanoparticles. The synthesized nanoparticles exhibited an average size of 296.47 ± 10 nm and a high drug encapsulation efficiency of 75%, and a drug loading of 10%. NAB-BTZ displayed a controlled, pH-sensitive release profile, with 59% release at pH 5.4 (mimicking tumor environments) and 46% at pH 7.4 after 12 h. In vitro assays demonstrated that NAB-BTZ significantly reduced the viability of 4T1 mammary carcinoma cells in a dose- and time-dependent manner, increasing late apoptosis from 6% to 54% after 48 h, compared to 24% for free BTZ. At molecular level, NAB-BTZ induced apoptosis by upregulating p53 and Bax, downregulating Bcl-2, and activating caspases 3 and 7. In vivo tests in a murine 4T1 breast cancer model showed that NAB-BTZ substantially inhibited tumor growth, achieving an average tumor volume of 916 mm³ by day 31 versus 1400 mm³ for free BTZ, leading to an improved survival rate of 100% compared to 83% in the BTZ group. Technetium-99m (^99mTc) labeling and SPECT imaging confirmed enhanced targeting capability, showing preferential accumulation of NAB-BTZ in tumor sites compared to free BTZ. These findings suggest that NAB-BTZ not only improves antitumor efficacy but also enhances its safety profile, underscoring its clinical potential in breast cancer therapy.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 5","pages":"2482-2493"},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951247","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":"Compatibility between Proteins and Polysaccharide Excipients in Oral Delivery Tablets.","authors":"Meng-Jia Jin, Zhen-Yi Jing, Li-Duo Liu, Aiping Zheng, Haibin Wang, Wei-Jie Fang","doi":"10.1021/acs.molpharmaceut.4c01413","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01413","url":null,"abstract":"<p><p>The development of oral protein biopharmaceuticals has gradually become a hot area of research. Currently, most of the added excipients are oral excipients used in traditional small molecule drugs, such as starch and lactose. However, the interaction between proteins and oral excipients has not received much attention. For example, the interaction may have an effect on protein stability, efficacy, etc. Herein, we observed a strong interaction between protein and sodium carboxymethyl starch (CMS), a common disintegrator in oral formulations of small molecule drugs. CMS can cause the complete disappearance of a free soluble protein in trastuzumab (TRA) tablets after reconstituted, as detected by size-exclusion high-performance liquid chromatography. While the other two polysaccharides with similar structures, hydroxyethyl starch and methylcellulose, exhibited no effect on the soluble TRA concentration. CMS produces an electrostatic interaction with TRA in a certain pH range, which affects the soluble protein monomer concentration and solution turbidity, increases the hydrophobicity of the TRA-CMS complex, and reduces the thermal stability of TRA, without changing its biological activity detected by an enzyme-linked immunosorbent assay. Thus, the CMS and TRA electrostatic binding is reversible, and CMS has a potential application in sustained release in oral monoclonal antibody (mAb) and protein delivery tablets. Mixed solutions of infliximab and etanercept (a fusion protein) with CMS at different pH were also studied by SE-HPLC. The results showed that the concentration of the free soluble protein detected by SE-HPLC was significantly and universally reduced when pH was below the isoelectric point, where the positively charged protein forms a strong electrostatic interaction with the negatively charged CMS. The structural characteristics of the protein (such as surface charge, surface hydrophobicity, etc.) should be fully considered in selecting the appropriate excipients for protein biopharmaceutical tablets.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951605","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}