Molecular Pharmaceutics最新文献

{"title":"A Novel Laboratory-Scale Pneumatic Tube System (PTS) Transportation Model to Assess the Impact of Hospital PTS Transportation on the Product Quality of Therapeutic Monoclonal Antibodies.","authors":"Kashappa Goud Desai, James D Colandene, Cait Sofa, Nathan Heacock, Ning Wang, Bivash Mandal, Brendan Blockus, Shin Lu","doi":"10.1021/acs.molpharmaceut.5c00428","DOIUrl":"10.1021/acs.molpharmaceut.5c00428","url":null,"abstract":"<p><p>The rapid and efficient transportation of therapeutic monoclonal antibody (mAb) dosing solutions, prepared in intravenous (IV) infusion containers (e.g., IV bags), from pharmacy departments to target locations within hospital campuses globally requires the use of pneumatic tube systems (PTSs). Evaluating the impact of hospital pneumatic tube system (PTS) transportation on the quality attributes of mAb dosing solutions poses significant challenges for pharmaceutical companies. Herein, we present a novel, first-of-its-kind laboratory-scale PTS transportation model capable of assessing the effects of hospital PTS transportation on the product quality of therapeutic mAbs. The laboratory-scale PTS transportation model generated shock and vibration stresses comparable to those experienced in a model hospital PTS transportation. The impact on the product quality of a test mAb due to model hospital PTS transportation was comparable to that observed with laboratory-scale PTS transportation. We found that the impact of PTS transportation on product quality was influenced by the cumulative stress levels experienced by the mAb. Additionally, the product quality was affected by the type of surfactant. The effectiveness of removing air headspace from an IV bag prior to PTS transportation, as a means to mitigate the product quality impact, was also influenced by cumulative PTS stress levels. PTS transportation, with or without stabilizing surfactant in the dosing solution, did not negatively affect the conformational stability, the tertiary structure, or the potency of the test mAb. This study demonstrates a practical approach for designing laboratory-scale PTS transportation studies to assess the risk to product quality of a given mAb due to hospital PTS transportation, determine the residual surfactant (e.g., polysorbate 80/PS80) level needed for protein stabilization, and establish safe transportation and handling practices when using hospital PTS systems.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"4183-4204"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264834","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":"Relaxation Processes in Freeze-Dried Monoclonal Antibody Formulations─The Role of Sucrose Concentration.","authors":"N S Krishna Kumar, Zhiyi Lin, Yunhua Chen, Cole W Tower, Evgenyi Shalaev, Ehab M Moussa, Raj Suryanarayanan","doi":"10.1021/acs.molpharmaceut.5c00378","DOIUrl":"10.1021/acs.molpharmaceut.5c00378","url":null,"abstract":"<p><p>Sucrose is the most common stabilizer used in freeze-dried protein formulations. We have investigated, using several methods, the effect of monoclonal antibody (mAb) to sucrose weight ratio on the thermal, relaxation, and water sorption behavior of freeze-dried formulations. The influence of the sucrose content on the miscibility and retention of the native structure of mAb was also investigated. With decreasing mAb-to-sucrose weight ratio, the following effects were observed. Differential scanning calorimetry revealed a progressive decrease in the glass transition temperature of the formulation, while, based on dielectric spectroscopy, the α-relaxation time decreased, whereas both the β- and γ-relaxation times increased. The ¹H <i>T</i>₁ relaxation time of the antibody, determined by solid-state nuclear magnetic resonance spectroscopy, followed the same trend as the β-relaxation time. Finally, infrared spectroscopy indicated that the optimal retention of the native-like secondary structure of the antibody was achieved at a 4:1 mAb-to-sucrose weight ratio. At mAb-to-sucrose weight ratios of 1:1 and lower, there was no evidence of phase separation in the 20-50 nm scale. Taken together, the results provide new insights into the solid-state behavior of the antibody-sucrose system.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"4125-4136"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264840","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":"Drug Delivery Mechanisms of Poly(glycerol sebacate): An In-Depth Study of the Energetics at the Molecular Scale.","authors":"Xavier Davoy, Julien Devémy, Pierre Fayon, Philip Chennell, Mehdi Sahihi, Sébastien Garruchet, Alain Dequidt, Patrice Hauret, Patrice Malfreyt","doi":"10.1021/acs.molpharmaceut.5c00102","DOIUrl":"10.1021/acs.molpharmaceut.5c00102","url":null,"abstract":"<p><p>Molecular simulations were carried out to investigate the mechanisms of drug delivery from poly(glycerol sebacate) (PGS). We simulated a number of key stages, from the encapsulation of the active pharmaceutical ingredients (API) in bulk PGS to their release into the water phase through the adsorption processes on the PGS surface. Caffeine, paracetamol, and ibuprofen were the studied APIs. Each stage of the API release was characterized by the calculation of a free energy property related to absorption, adsorption, or association. The free energy of absorption showed that the PGS material is able to accommodate APIs of different polarities and hydration properties due to the presence of hydrophobic and hydrophilic regions in the material. The free energy values of adsorption of the APIs on the PGS surface remain favorable, whereas the free energies of binding between APIs and glycerol, sebacic acid, and prepolymer molecules are weaker, thus indicating a possible release of the APIs into water from an energy viewpoint.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"3848-3859"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323852","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":"Microbiota-Mediated Modulation of Chemotherapeutic Drug Efficacy in Colorectal Cancer: An In-Depth Analysis of Six Key Drugs.","authors":"Priyanka Dalal, Nandini Bajaj, Uttkarsh Katiyar, Deepika Sharma","doi":"10.1021/acs.molpharmaceut.5c00587","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00587","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a major health burden, and emerging evidence suggests that gut microbiota may influence therapeutic responses. This study explores the interaction between <i>Escherichia coli</i> and non-CRC-specific anticancer drugs cyclophosphamide, Cytalon, Nitrol, etoposide, gemcitabine, and methotrexate through bacterial modification. Following bacterial incubation, drugs were tested <i>in vitro</i> using MTT and Alamar Blue assays, revealing significantly enhanced cytotoxicity against CRC cells (HCT116) while preserving variability in normal fibroblasts (L929). Mechanistic studies, including ROS production, mitochondrial membrane potential loss, cell cycle arrest, NF-κB translocation, and TNF-α activation confirmed the cell death induction. NMR analysis and 3D spheroid disruption demonstrated structural drug alterations postincubation in one of the best-responding drugs. These findings highlight microbial drug transformation as a promising avenue for enhancing chemotherapeutic selectivity and efficacy in colorectal cancer treatment.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582664","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 the Potential of PLGA Nanoparticles for Enhancing Pulmonary Drug Delivery.","authors":"Mirsiane Pascoal Costa, João Octavio Carneiro Abdu, Maria Fernanda Cobucci Soares de Moura, Allana Carvalho Silva, Thiago Medeiros Zacaron, Mayara Rodrigues Brandão de Paiva, Rodrigo Luiz Fabri, Frederico Pittella, Ítalo Tuler Perrone, Guilherme Diniz Tavares","doi":"10.1021/acs.molpharmaceut.5c00118","DOIUrl":"10.1021/acs.molpharmaceut.5c00118","url":null,"abstract":"<p><p>Lung diseases remain a leading cause of mortality globally, posing a substantial challenge to public health. Conditions such as asthma, tuberculosis, cystic fibrosis, pneumonia, chronic obstructive pulmonary disease (COPD), and lung cancer are highly prevalent and of increasing concern due to their rising incidence in recent years. The recent global outbreak of coronavirus disease 2019 (COVID-19) has further highlighted the urgent need for more effective therapeutic approaches to combat pulmonary diseases. In this context, growing interest in nanotechnology for pulmonary drug delivery has emerged, driven by its potential to enable localized treatment, reduce dosages, provide controlled release, enhance drug solubility, and improve bioavailability. Among the various nanomaterials explored, poly(lactic-<i>co</i>-glycolic acid) (PLGA)─a copolymer of lactic and glycolic acids─has gained regulatory approval as a safe, biodegradable, and biocompatible carrier, with an extended-release profile, making it an ideal candidate for the development of nanostructured drug delivery systems. Multiple methodologies are available for synthesizing PLGA nanoparticles tailored to pulmonary administration, supported by a wide array of devices designed to cater to individual patient needs. This review seeks to evaluate the advantages of PLGA-based nanoparticles for pulmonary drug delivery, with a focus on their potential to enhance inhalation therapy formulations.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"3542-3562"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245352","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":"","authors":"Kenneth C. Waterman*,&nbsp;Maria J. Krisch,&nbsp;Tyler J. McDonald,&nbsp;Rebekah Theriault,&nbsp;Chris Wood,&nbsp;Michael D. Bielak,&nbsp;Connie Tang and Jana O’Donnell,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144569156","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":"","authors":"Kaili Wang,&nbsp;Chunjing Guo,&nbsp;Xue Dong,&nbsp;Yueming Yu,&nbsp;Bingjie Wang,&nbsp;Wanhui Liu and Daquan Chen*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00583","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144569161","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":"","authors":"Marco Tjakra,&nbsp;Nopdanai Chakrapeesirisuk,&nbsp;Magdalena Jacobson,&nbsp;Mikael E. Sellin,&nbsp;Jens Eriksson,&nbsp;Alexandra Teleki and Christel A. S. Bergström*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00298","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144569162","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":"","authors":"Siddhant Kumar,&nbsp;Akshay Yadav,&nbsp;Rahul K. Verma,&nbsp;Akhilesh Kumar,&nbsp;Piyush Kumar Gupta and Rahul Shukla*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144569163","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":"","authors":"Jitong Wang,&nbsp;Fan Zhao,&nbsp;Yu Zhang,&nbsp;Yuting Wen,&nbsp;Wenxu Wang,&nbsp;Jinru Hu,&nbsp;Chun Qiao,&nbsp;Ruixiang Li* and Ruofei Du*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.4c01383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144569165","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}