Molecular Pharmaceutics最新文献_第10页

Voices in Molecular Pharmaceutics: Meet Dr. Herma Pierre, Dedicated to Developing Safer and More Effective Therapeutics. 分子药剂学的声音：认识Herma Pierre博士，致力于开发更安全，更有效的治疗方法。

IF 4.5 2区医学

Molecular Pharmaceutics Pub Date : 2025-05-05 Epub Date: 2025-03-07 DOI: 10.1021/acs.molpharmaceut.5c00283

Herma Pierre

引用次数: 0

Purpurin/Indocyanine Green Nanocomposite for Restricting Glutaminolysis to Enhance Dual Phototherapy of Cancer. 紫嘌呤/吲哚菁绿纳米复合材料抑制谷氨酰胺水解增强肿瘤双重光疗。

IF 4.5 2区医学

Molecular Pharmaceutics Pub Date : 2025-05-04 DOI: 10.1021/acs.molpharmaceut.5c00001

Sen Li, Shenyi Wang, Yanfei Cai, Dong Hua, Jian Jin, Hao Zhang, Zhaoqi Yang

{"title":"Purpurin/Indocyanine Green Nanocomposite for Restricting Glutaminolysis to Enhance Dual Phototherapy of Cancer.","authors":"Sen Li, Shenyi Wang, Yanfei Cai, Dong Hua, Jian Jin, Hao Zhang, Zhaoqi Yang","doi":"10.1021/acs.molpharmaceut.5c00001","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00001","url":null,"abstract":"Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising noninvasive cancer treatments owing to their precision and convenience. Indocyanine green (ICG), a dual-functional agent capable of generating both PDT and PTT effects under single-wavelength laser irradiation, is widely explored in oncology. However, ICG faces limitations such as poor bioavailability, rapid systemic clearance, and tumor microenvironment glutathione (GSH) overexpression, which scavenges reactive oxygen species (ROS) and diminishes therapeutic efficacy. To address this, we developed albumin-based nanoparticles (ICG&purpurin@BSA) co-encapsulating ICG and purpurin. Purpurin inhibits mitochondrial glutaminolysis, a metabolic pathway critical for GSH synthesis, thereby reducing GSH-mediated ROS depletion. Flow cytometry and Western blot analyses confirmed significant GSH downregulation. The nanocomposite demonstrated robust anticancer effects in vitro and in vivo, achieving near 90% tumor growth suppression within 12 days. The outcomes of this research demonstrate the benefits of combining biocompatible nanocomposites with glutamine pathway inhibitors and dual phototherapy agent ICG.","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951453","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}

引用次数: 0

Next-Generation Transformable Nanomedicines: Revolutionizing Cancer Drug Delivery and Theranostics. 下一代可转化纳米药物：革命性的癌症药物输送和治疗。

IF 4.5 2区医学

Molecular Pharmaceutics Pub Date : 2025-05-03 DOI: 10.1021/acs.molpharmaceut.4c01495

Swapnil Shinde, Saurabh Shah, Paras Famta, Suraj Wagh, Giriraj Pandey, Abhishek Sharma, Ganesh Vambhurkar, Akshita Jain, Saurabh Srivastava

{"title":"Next-Generation Transformable Nanomedicines: Revolutionizing Cancer Drug Delivery and Theranostics.","authors":"Swapnil Shinde, Saurabh Shah, Paras Famta, Suraj Wagh, Giriraj Pandey, Abhishek Sharma, Ganesh Vambhurkar, Akshita Jain, Saurabh Srivastava","doi":"10.1021/acs.molpharmaceut.4c01495","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01495","url":null,"abstract":"Nanomedicine has significantly advanced the treatment of various cancer phenotypes, addressing numerous challenges associated with conventional therapies. Researchers have extensively investigated the physicochemical properties of nanocarriers, such as charge, morphology, and surface chemistry, to optimize drug delivery systems. In the context of transformable nanomedicine, these properties are particularly critical for overcoming existing limitations, including suboptimal blood circulation times, sequestration by the reticuloendothelial system and mononuclear phagocyte system, and inefficient targeting of the tumor microenvironment (TME). Alterations in nanocarrier geometry, surface charge, and hydrophilicity have shown potential in mitigating these barriers, offering improved therapeutic outcomes and enhanced biomedical applications. This review explores controlled modulation of these properties in the context of anticancer therapy, offering an in-depth exploration of transformable strategies activated by both internal and external stimuli. We analyze the implications of these tunable characteristics on pharmacokinetics, biodistribution, and targeted delivery to the TME. Additionally, we address the current challenges in the clinical translation of these advanced nanocarriers and propose strategies to overcome these obstacles to enhance the clinical feasibility of nanomedicine-based cancer therapies.","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955611","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}

引用次数: 0

CD7-Targeted Cytotoxic Potency of Diphtheria Toxin- and Ricin-Based Immunotoxins in Targeted Therapy for T-Cell Acute Lymphoblastic Leukemia. 基于白喉毒素和蓖麻毒素的免疫毒素靶向治疗t细胞急性淋巴细胞白血病的cd7靶向细胞毒性

IF 4.5 2区医学

Molecular Pharmaceutics Pub Date : 2025-05-02 DOI: 10.1021/acs.molpharmaceut.5c00146

Hyun Bin Lee, Seong Guk Park, Hyo Jeong Kim, Jun Pyo Jeon, SuHyeon Oh, SangJoon Lee, Sung Ho Park, Sebyung Kang

{"title":"CD7-Targeted Cytotoxic Potency of Diphtheria Toxin- and Ricin-Based Immunotoxins in Targeted Therapy for T-Cell Acute Lymphoblastic Leukemia.","authors":"Hyun Bin Lee, Seong Guk Park, Hyo Jeong Kim, Jun Pyo Jeon, SuHyeon Oh, SangJoon Lee, Sung Ho Park, Sebyung Kang","doi":"10.1021/acs.molpharmaceut.5c00146","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00146","url":null,"abstract":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and heterogeneous hematologic malignancy, underscoring the urgent need for innovative treatments such as immunotoxins, which combine specific antigen targeting with potent cytotoxic activity. In this study, we developed two distinct immunotoxins (aCD7Nb/DTA and RTA/aCD7Nb) by combining the CD7-binding nanobody (aCD7Nb) with recombinant diphtheria toxin (DTA) and ricin (RTA), utilizing SpyCatcher/SpyTag (SC/ST) post translational protein ligation system for targeted therapy in T-cell acute lymphoblastic leukemia (T-ALL). Both aCD7Nb/DTA and RTA/aCD7Nb specifically bind to three CD7-expressing T-ALL cell lines, CCRF-CEM, Jurkat, and MOLT-4 cells, based on CD7 expression levels, but not to the CD7-negative Raji B-ALL cells. Both aCD7Nb/DTA and RTA/aCD7Nb demonstrated high cytotoxic against T-ALL cells, with IC50 values inversely correlated to CD7 expression. Notably, RTA/aCD7Nb exhibited approximately 2-fold higher anticancer efficacy compared to aCD7Nb/DTA in both CCRF-CEM and Jurkat cells. In an orthotopic model of CCRF-CEM T-ALL-engrafted NSG mice, systemic administration of RTA/aCD7Nb effectively inhibited T-ALL progression and extended survival, without any adverse effects. These findings underscore the potential of combining a CD7-binding ligand with an appropriate active toxin moiety to significantly enhance the efficacy of immunotoxins against T-ALL.","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951297","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}

引用次数: 0

Caffeic Acid-Biogenic Amine Complexes Outperform Standard Drugs in Reducing Toxicity: Insights from In Vivo Iron Chelation Studies. 咖啡酸-生物胺复合物在降低毒性方面优于标准药物：来自体内铁螯合研究的见解。

IF 4.5 2区医学

Molecular Pharmaceutics Pub Date : 2025-05-02 DOI: 10.1021/acs.molpharmaceut.4c01424

Pranathi Tata, Aparajita Ghosh, Trinath Jamma, Onkar Kulkarni, Ramakrishnan Ganesan, Jayati Ray Dutta

{"title":"Caffeic Acid-Biogenic Amine Complexes Outperform Standard Drugs in Reducing Toxicity: Insights from In Vivo Iron Chelation Studies.","authors":"Pranathi Tata, Aparajita Ghosh, Trinath Jamma, Onkar Kulkarni, Ramakrishnan Ganesan, Jayati Ray Dutta","doi":"10.1021/acs.molpharmaceut.4c01424","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01424","url":null,"abstract":"Iron homeostasis imbalance, caused by conditions such as thalassemia, sickle cell anemia, and myocardial infarction, often results in elevated free iron levels, leading to ferroptosis and severe organ damage. While current iron chelators like deferoxamine (DFO) and deferiprone are effective, they are associated with significant side effects, including nephrotoxicity, gastrointestinal bleeding, and liver fibrosis. This creates an urgent need for safer, natural-product-based alternatives for effective iron chelation therapy (ICT). This study investigates caffeic acid (CA)-based complexes with biogenic amines, specifically spermine (CA-Sp) and histidine (CA-His), as potential ICT candidates. Initial in vitro assays on HEK-293 cells under iron dextran (ID)-induced toxicity have demonstrated their protective effects, with CA-Sp exhibiting superior efficacy. The in vivo studies in mice have further validated their potential, showing remarkable iron chelation and toxicity mitigation compared to DFO. Inductively coupled plasma mass spectrometry (ICP-MS) reveals significant iron excretion in fecal matter in the treatment group along with reductions in serum ferritin levels. The markers of nephrotoxicity (creatinine) and liver function (ALT, AST) have also been shown to be normalized in treated groups, while immunological analyses have revealed restored levels of neutrophils, T cells, and B cells. Additionally, the inflammatory cytokines, TNF-α and IL-6, have exhibited significant reductions, with the CA-based formulations surpassing the effects of DFO. Histological analyses using Prussian blue staining have further confirmed reduced iron deposition in vital organs such as the liver, kidney, and spleen. These findings highlight CA-Sp as a particularly promising candidate for ICT, offering a safer and more effective strategy for managing iron overload and its associated complications.","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956708","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}

引用次数: 0

Enantiomeric Excess Bupivacaine in a Lavender Oil NLC Tested in a Melanoma Model: Prolonged Release and Anticancer Effect. 薰衣草油NLC中过量布比卡因对映体在黑色素瘤模型中测试：延长释放和抗癌作用。

IF 4.5 2区医学

Molecular Pharmaceutics Pub Date : 2025-05-01 DOI: 10.1021/acs.molpharmaceut.5c00254

Gabriela Geronimo, Gustavo H Rodrigues da Silva, Ludmilla D de Moura, Fabíola V de Carvalho, Talita C Mendonça, Laura B Olivo, Bibiana Verlindo de Araújo, Teresa C Dalla Costa, Luccas Lavareze, Fernanda V Mariano, Eneida de Paula

{"title":"Enantiomeric Excess Bupivacaine in a Lavender Oil NLC Tested in a Melanoma Model: Prolonged Release and Anticancer Effect.","authors":"Gabriela Geronimo, Gustavo H Rodrigues da Silva, Ludmilla D de Moura, Fabíola V de Carvalho, Talita C Mendonça, Laura B Olivo, Bibiana Verlindo de Araújo, Teresa C Dalla Costa, Luccas Lavareze, Fernanda V Mariano, Eneida de Paula","doi":"10.1021/acs.molpharmaceut.5c00254","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00254","url":null,"abstract":"Recent studies have highlighted the potential of local anesthetics (LA) as adjuvants in cancer treatment, specifically by increasing survival rates when used in surgical excisions. However, the clinical use of LA is restricted due to their systemic toxicity. The development of drug delivery systems could address this issue and advance the utilization of these molecules. In this research, we explored the pharmacokinetics (using microdialysis probes) and antitumor properties of a nanostructured lipid carrier (NLC) formulation containing the commercially available enantiomeric excess form of bupivacaine (BVCS75). This NLC was prepared with lavender oil (NLC-L-BVC), an excipient with inherent antitumor properties. We compared this formulation to a control (NLC-BVC) using synthetic lipids. Pharmacokinetic assessments of the NLCs confirmed the sustained release of BVCS75 within the tumor, characterized by a reduced elimination rate constant and longer half-life (∼6×). The encapsulation of BVCS75 within nanoparticles (whether natural or synthetic) enhanced its effectiveness in treating the primary tumor, resulting in the inhibition of tumor growth (70% with NLC-L-BVC and 72% with NLC-BVC), outperforming free BVC (17% inhibition). However, the association of lavender oil with BVCS75 in an NLC did not yield synergistic properties. Furthermore, all BVCS75 treatments (whether free or encapsulated) improved animal survival rates. These findings confirm that encapsulation of bupivacaine in NLC can prolong drug action at the local site, contributing to improved local antitumor therapy while mitigating systemic effects.","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952732","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}

引用次数: 0

Synthesis and Biological Evaluation of ¹³¹I-Risedronate with Bone Targeting Activity. 具有骨靶向活性的131i -利塞膦酸盐的合成及生物学评价

IF 4.5 2区医学

Molecular Pharmaceutics Pub Date : 2025-05-01 DOI: 10.1021/acs.molpharmaceut.5c00300

Zehui Lin, Wangxi Hai, Pengfei Pan, Jin-Hong Lin, Biao Li, Ji-Chang Xiao

引用次数: 0

Engineered Peptide Coacervates Enable Efficient Intracellular Delivery of the MYC Inhibitor omoMYC. 工程肽凝聚体能够有效地在细胞内递送MYC抑制剂omoMYC。

IF 4.5 2区医学

Molecular Pharmaceutics Pub Date : 2025-04-30 DOI: 10.1021/acs.molpharmaceut.5c00468

Carmine P Cerrato, Martin Krkoška, Yue Sun, Judit Liaño-Pons, Qi Ying Neo, Thibault Vosselman, Mohammad Alzrigat, Borek Vojtěšek, David P Lane, Marie Arsenian Henriksson, Ali Miserez, Michael Landreh

{"title":"Engineered Peptide Coacervates Enable Efficient Intracellular Delivery of the MYC Inhibitor omoMYC.","authors":"Carmine P Cerrato, Martin Krkoška, Yue Sun, Judit Liaño-Pons, Qi Ying Neo, Thibault Vosselman, Mohammad Alzrigat, Borek Vojtěšek, David P Lane, Marie Arsenian Henriksson, Ali Miserez, Michael Landreh","doi":"10.1021/acs.molpharmaceut.5c00468","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00468","url":null,"abstract":"Intracellular delivery is a bottleneck in the development of therapeutic peptides and proteins. Here, we demonstrate the efficient delivery of omoMYC, the first MYC inhibitor in clinical trials, using HBpep-SP, an engineered peptide forming liquid-liquid phase-separated coacervates. HBpep-SP coacervates facilitate efficient cellular uptake and intracellular delivery of the omoMYC peptide at concentrations lower than those required for spontaneous uptake. Strikingly, omoMYC coacervates result in reduced proliferation and apoptosis induction in the low c-MYC expressing cell lines HEK293 and SH-SY5Y cells, but not in HeLa and SK-N-BE(2) cells with high c-MYC/MYCN expression, respectively, suggesting that endogenous MYC/N levels may impact the effects of omoMYC. Importantly, our approach bypasses the need for cell penetration-enhancing chemical modifications, offering a novel strategy for the investigation of peptide drug mechanisms in therapeutic development.","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951083","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}

引用次数: 0

Development of Structurally Identical Therapeutic and Diagnostic Agents for Image-Guided Boron Neutron Capture Therapy: c(RGD-BPA-K) Peptide with ¹²⁵I/^natI Albumin-Binding Moiety. 具有125I/natI白蛋白结合片段的c（RGD-BPA-K）肽在图像引导硼中子俘获治疗和诊断中的应用

IF 4.5 2区医学

Molecular Pharmaceutics Pub Date : 2025-04-30 DOI: 10.1021/acs.molpharmaceut.5c00291

Iqra Bibi, Kyung Jun Kang, Jung Young Kim, Sajid Mushtaq, Ji-Ae Park

{"title":"Development of Structurally Identical Therapeutic and Diagnostic Agents for Image-Guided Boron Neutron Capture Therapy: c(RGD-BPA-K) Peptide with 125I/natI Albumin-Binding Moiety.","authors":"Iqra Bibi, Kyung Jun Kang, Jung Young Kim, Sajid Mushtaq, Ji-Ae Park","doi":"10.1021/acs.molpharmaceut.5c00291","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00291","url":null,"abstract":"The development of boron neutron capture therapy (BNCT) agents and structurally similar radiolabeled counterparts for diagnostic imaging is an area of significant interest. In this study, we designed structurally same compounds, c(RGD-BPA-K)(PEG2-(4-iodophenylbutyl)) (compound 1) and its radioiodinated counterpart, c(RGD-BPA-K)(PEG2-(4-[125I]iodophenylbutyl)) ([125I]1), for efficient BNCT and SPECT/CT imaging, respectively. An albumin-binding moiety was introduced into the compound to enhance the blood circulation time and tumor accumulation. We evaluated the efficacy of compound 1 and [125I]1 in U87MG tumor-bearing mice using SPECT/CT imaging, biodistribution analysis, and inductively coupled plasma mass spectrometry. Both compound 1 and [125I]1 displayed similar pharmacokinetics, high blood retention, and substantial accumulation in U87MG tumors. This study highlights the potential of compound 1 and [125I]1 for SPECT/CT-guided BNCT. The structural identity between the therapeutic and diagnostic agents in BNCT can enhance its therapeutic efficacy. Further structural modifications to increase boron concentration in tumors, as well as thermal neutron irradiation studies, may be necessary to fully explore the potential of our novel BNCT agent.","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952129","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}

引用次数: 0

Pharmaceutical Analysis of Protein-Peptide Coformulations and the Influence of Polysorbates. 蛋白-肽共制剂的药理分析及聚山梨酸酯的影响。

IF 4.5 2区医学

Molecular Pharmaceutics Pub Date : 2025-04-30 DOI: 10.1021/acs.molpharmaceut.5c00119

Joseph Whiteley, Susanna Abrahmsén-Alami, Jonathan Booth, Steve Mellor, James Humphrey, Laura J Waters

{"title":"Pharmaceutical Analysis of Protein-Peptide Coformulations and the Influence of Polysorbates.","authors":"Joseph Whiteley, Susanna Abrahmsén-Alami, Jonathan Booth, Steve Mellor, James Humphrey, Laura J Waters","doi":"10.1021/acs.molpharmaceut.5c00119","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00119","url":null,"abstract":"Coformulation is an approach to formulating multiple biopharmaceutical therapeutics in a single formulation, promising the benefits of both therapies in one dose. However, as molecular stability is a key consideration in traditional biopharmaceutical formulations, stability of coformulations will require extensive investigation. This study evaluated the effects of traditional formulation stabilizers, specifically surfactants, at different grades, namely, regular grade (RG) Tween 20 and Tween 80 and Super-refined Polysorbate 20 and 80. Their effects were assessed through their interactions with human serum albumin (HSA) and a glucagon-like peptide-1 (GLP-1) receptor agonist (MEDI7219). Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) were implemented to determine the strength of the binding interactions and thermal stability of the tertiary system. ITC confirmed that upon titration of MEDI7219 into a solution of HSA and RG, Tween 20 the binding affinity of the peptide was reduced, resulting in negatively cooperative binding. However, when the peptide was titrated into a solution of HSA and both grades of Tween 80, the binding affinity increased with positive cooperative binding. DSC established that MEDI7219 increased the thermal stability of HSA to a similar extent to the polysorbates. Combining peptide and polysorbate did not further increase the thermal stability of HSA; however, it did reduce the unfolding of HSA molecules in the absence of heat. Overall, the unique findings in this study have demonstrated that the order of addition in a ternary coformulation affects the final composition which is an important consideration for pharmaceutical development.","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951451","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}

引用次数: 0