Molecular Pharmaceutics最新文献

{"title":"Slurry Conversion: A General Method for Formulating Amorphous Solid Dispersions and Fully Integrating Drug and Polymer Components.","authors":"Amy Lan Neusaenger, Caroline Fatina, Yichun Shen, Junguang Yu, Lian Yu","doi":"10.1021/acs.molpharmaceut.5c00240","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00240","url":null,"abstract":"<p><p>A solvent-sparing method, called \"slurry conversion\", has been tested as a general approach to preparing amorphous solid dispersions (ASDs). In this method, a solid mixture of a drug and a polymer is stirred in the presence of a small quantity of a solvent, which is subsequently removed. In previous work, the method enabled more complete salt formation between lumefantrine (LMF), a basic antimalarial, with acidic polymers, than the common methods of hot melt extrusion and spray drying, leading to improved physical stability and release. Here, we apply this method to 18 poorly soluble drugs formulated as binary and ternary ASDs. For a rigorous test, the drugs were formulated with a single polymer, poly(acrylic acid) (PAA), under the same condition: room temperature stirring in 1:1 ethanol-dichloromethane at 4:1 solvent/solid ratio. ASDs were prepared for 16 of the 18 drugs at 25% drug loading and 11 at 50% drug loading. The drugs that were not fully amorphized did not dissolve in the default solvent or crystallized during drying. For most drugs, an abrupt \"clearing\" of the slurry occurred during stirring, indicating complete dissolution and amorphization before drying. While clearing did not occur for some drugs (e.g., clofazimine), the product was still fully amorphous, through solvent-mediated conversion. For a basic drug, the degree of protonation by PAA increases smoothly with PAA concentration and is ordered by its basic strength, supporting the conclusion that the method allows the system to reach thermodynamic equilibrium. In addition to binary ASDs, ternary ASDs containing two drugs (LMF and artemether or LMF and artesunate) were successfully prepared to support applications in combination therapies. In these ternary formulations, the protonation of LMF follows the trend established for binary systems. We find that slurry conversion can be scaled up 60-fold from the typical batch size without any difficulties or adverse effect on the structure and properties of the product. Overall, our results demonstrate that slurry conversion is a general, low-cost, and green alternative to conventional methods for manufacturing ASDs where the components are fully integrated.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289349","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":"A Synergistically Enhanced Near-Infrared ESIPT Fluorescent Probe for High-Performance In Situ Imaging of Cellular Apoptosis.","authors":"Qian Lei, Xiang Cheng, Qian Chen, Xiaoqian Ma, Wei Wang, Pengfei Rong, Bin Feng, Shengwang Zhang, Wenbin Zeng","doi":"10.1021/acs.molpharmaceut.5c00615","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00615","url":null,"abstract":"<p><p>Monitoring apoptotic progression is critical for tracking disease development and evaluating therapeutic interventions. Fluorescent probes that integrate aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) offer some advantages, including large Stokes shifts, high quantum yields in the aggregated state, and strong photostability. In this study, we developed an ESIPT-based fluorescent probe, <b>ABTT-DEVD</b>, with AIE properties for the highly sensitive detection of caspase-3 and real-time imaging of apoptosis. The probe design incorporates a hydrophilic DEVD peptide substrate linked to a hydrophobic ESIPT fluorophore. Caspase-3-mediated cleavage induces a significant change in water solubility, leading to strong fluorescence enhancement with an ultralow detection limit of 1.2 pM. Molecular docking studies corroborate the specific interaction of the DEVD peptide with the caspase-3 active site. Furthermore, <b>ABTT-DEVD</b> enabled the visualization of endogenous caspase-3 activity in living cells, facilitating the evaluation of antitumor drug efficacy. The probe's effectiveness in tracking apoptosis progression is further supported by fluorescence data and flow cytometry analysis, underscoring its potential as a valuable tool for apoptosis monitoring in biomedical research.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264835","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":"Application of Biomaterials in the Development of Enteric-Coated Luminar Capsule Microneedles for Selective Delivery of Sofosbuvir to the Liver: A Promising Treatment for Hepatitis C.","authors":"Musyfira Sahra, Nurul Fitrayani, Abigael Alik Samma, Christopher Kosasi Ko, Felicia Virginia Thios, Andi Dian Permana","doi":"10.1021/acs.molpharmaceut.4c01529","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01529","url":null,"abstract":"<p><p>In commercial applications, sofosbuvir (SOF) for hepatitis C is only available in tablet dosage form, resulting in minimal SOF accumulation in the liver (26.94%) due to its low intestinal permeability and high molecular weight (529.5 Da). Therefore, in this study, luminar capsule microneedles (LUCAMs) were developed, in which SOF was delivered via dissolving microneedles (DMN) attached to a branch and encapsulated in an enteric-coated hard capsule designed to dissolve exclusively in the intestinal environment. The needle on the DMN has the potential to facilitate SOF absorption in the intestine, thereby enabling maximum absorption. A thorough evaluation of DMN, branches, and capsules was conducted, encompassing formulation, characterization, differential scanning calorimetry, and dissolution time. This comprehensive evaluation demonstrated that the results obtained align with the established specifications. Furthermore, a series of evaluations, including capsule coating, revealed that the capsules dissolve selectively under intestinal pH conditions, as indicated by a hemolysis assay and irritation potential levels below 5%. These findings collectively demonstrate that the utilized biomaterial is nontoxic and nonirritating. In vitro and ex vivo permeability studies demonstrated that LUCAMs released 99.32 ± 11.92 and 203.97 ± 19.78 μg/mL SOF within 24 h, respectively. In vivo studies were conducted on two groups, namely, LUCAMs and controls, with measurements taken at 12, 24, and 36 h. The results demonstrated a significant increase in SOF concentration in the liver, reaching 1.26 ± 0.18 μg/mL in the LUCAM group by 36 h, in contrast to the control group, which was only detected at 12 h (0.83 ± 0.13 μg/mL) and not detected at 24 and 36 h. Histopathological analysis confirmed the absence of severe tissue damage, indicating that LUCAMs are a promising approach for enhancing the delivery of SOF to the liver and improving the efficacy of hepatitis C treatment.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273707","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":"https://doi.org/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":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","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":"Correction to \"Endotracheal Aerosolization Device for Laboratory Investigation of Pulmonary Delivery of Nanoparticle Suspensions: In Vitro and in Vivo Validation\".","authors":"Zhengwei Huang, Ying Huang, Cheng Ma, Xiangyu Ma, Xuejuan Zhang, Ling Lin, Ziyu Zhao, Xin Pan, Chuanbin Wu","doi":"10.1021/acs.molpharmaceut.5c00752","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00752","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273708","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":"Tumor-Specific Activatable Nanopaltform Achieves Oxidative Stress Amplification and Reversal of Cisplatin Resistance to Provoke Enhanced Ferroptosis-Apoptosis Cancer Therapy.","authors":"Jieming Zhang, Fangfang Zhou, Xin Du, Meiru Zhang, Suxiao Li, Songtao Niu, Qungang Chang, Yongju He","doi":"10.1021/acs.molpharmaceut.5c00406","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00406","url":null,"abstract":"<p><p>Cisplatin-based chemotherapy is widely used to combat cancers through an apoptosis pathway. However, drug resistance induced by upregulated glutathione (GSH) in tumor cells and systemic side effects significantly compromise its therapeutic efficacy. The application of nanocarriers with a GSH-scavenging ability is a promising strategy to overcome these obstacles. In addition, ferroptosis has shown great potential in eliminating the limitation of apoptosis-mediated chemotherapeutics. Herein, a multifunctional nanoplatform (S4MON-Cis@TA-Fe³⁺), loaded with cisplatin in tetrasulfide bonds-bridged mesoporous organosilica nanoparticles (S4MON) and then coated with tannic acid (TA)-Fe³⁺ metal-phenolic network, is developed for apoptosis-ferroptosis synergistic therapy. In the acidic tumor cells, the outer TA-Fe³⁺ network is disassembled into Fe³⁺ and TA, and the internal S4MON-Cis network is exposed. The released TA and endogenous GSH reduce Fe³⁺ to Fe²⁺, which significantly increases cellular oxidative stress through the Fenton reaction and GSH consumption. Moreover, S4MON-Cis decreases the intracellular GSH content through redox reaction between tetrasulfide bonds and GSH, which further augments cellular oxidative stress and triggers nanoparticle degradation to release cisplatin. Subsequently, cisplatin induces apoptosis and elevates the cellular hydrogen peroxide level to improve the Fenton reaction efficiency. The multiple oxidative stress amplification greatly promotes lipid peroxidation and glutathione peroxidase 4 downregulation, boosting tumor ferroptosis. Meanwhile, the dual GSH elimination significantly improves the antitumor effect of cisplatin. As a result, S4MON-Cis@TA-Fe³⁺ exhibits effective tumor growth inhibition through self-enhanced apoptosis-ferroptosis synergistic therapy, which holds great promise for cancer therapy.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273709","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":"Aptasensing Technology and Its Potential Applications: Where Do We Stand?","authors":"Jhilik Roy, Neelanjana Bag, Shubham Roy, Dhananjoy Mondal, Tingting Gong, Rajib Mondal, Bing Guo, Ruma Basu, Sukhen Das","doi":"10.1021/acs.molpharmaceut.5c00352","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00352","url":null,"abstract":"<p><p>Aptamers, valued for their stability, target affinity, and modifiability, have advanced biosensing, yet key challenges hinder their translation into practical sensing platforms. This work explores the future potential of aptasensing technologies across various fields, such as clinical chemistry, quality control, protein analysis, wastewater treatment, nanomaterial characterization, forensic evidence analysis, animal health monitoring, heavy metal detection, security, machine learning, and AI in aptamer design. This review also provides a detailed discussion of their underlying molecular mechanisms, highlighting their applications and effectiveness. Herein, numerous challenges in the field and potential solutions have been proposed, which could expedite the selection of the aptasensing paradigm for future usage and aid in diversifying aptasensors. This review aims to update researchers in biomedical engineering, materials science, clinical microbiology, and food science, advancing aptasensors toward clinical application.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264836","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":"Cerebrospinal Fluid Flow Enhancement (CFE) Increases the Spatial Distribution of Methotrexate after Intracerebroventricular Administration in a Sheep Model.","authors":"Hector Ribeiro Benatti, Toloo Taghian, Olivia Mihalek, Sarah Nath, Jillian Gallagher, Abigail McElroy, Erin F Hall, Rrita Daci, Nathan K Yingling, William C Baker, Susan Tuominen, Lindsey Bierfeldt, Xuntian Jiang, Heather L Gray-Edwards, Rachael W Sirianni","doi":"10.1021/acs.molpharmaceut.4c01030","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01030","url":null,"abstract":"<p><p>For the treatment of central nervous system (CNS) neoplasias, achieving widespread chemotherapy distribution throughout the brain remains a major challenge. Direct infusion of substances into the cerebrospinal fluid (CSF) is one method to bypass the blood-brain barrier (BBB) and increase the exposure of CNS tissues to therapeutic molecules. As of 2024, only a handful of drugs are FDA-approved for CSF administration, including morphine, baclofen, ziconotide, and methotrexate. However, despite the use of these approaches in clinical practice, relatively little is understood regarding the spatial distribution of CSF-administered agents, and these distributions remain to be optimized. Here, we focus on methotrexate (MTX), which is an antifolate antineoplastic agent that has been administered intrathecally to treat numerous conditions, including inflammatory and oncologic diseases. We examined the time course of the distribution of MTX to gain insight into the flow dynamics and hypothesized that CSF flow enhancement (CFE), i.e., manipulation of the pattern by which CSF moves within the CNS, would alter the spatial distribution of MTX in the CNS following CSF administration. This hypothesis was tested with a recirculating device, which we used to continuously recirculate fluid from the intracerebral lateral ventricles (ICV) to the cisterna magna (CM). Our experimental results provide detailed maps of the spatial distribution of MTX following CSF administration in sheep and support our expectation that CFE is an effective method to manipulate CNS drug distribution.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264837","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":"In Vitro and In Vivo Study of Novel PSMA-Targeted Radioligands: Enhancing Tumor Uptake and Therapeutic Efficacy through Zwitterionization and Albumin-Binding Strategies.","authors":"Yang Liu, Haiyang Li, Han Zhou, Hongmei Yuan, Yan Zhao, Zhicong Yang, Sufan Tang, Tongtong Wu, Li Wang, Zhanwen Huang, Yue Chen, Nan Liu, Zhijun Zhou","doi":"10.1021/acs.molpharmaceut.5c00214","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00214","url":null,"abstract":"<p><p>Prostate-specific membrane antigen (PSMA) targeted radioligand therapy (TRT) for metastatic castration-resistant prostate cancer has demonstrated significant potential. This study aimed to develop an optimal radiotherapeutic agent suitable for high-level PSMA expression by optimizing the ligand structure with albumin-binding zwitterionic strategies to increase tumor uptake and retention time and to explore the effects of these strategies on the in vitro and in vivo properties of PSMA inhibitors. All precursors were synthesized based on PSMA-targeting agent Flu-1. The radioligands were investigated for their physicochemical properties, imaging, and biodistribution by means of gallium and lutetium labeling to evaluate their pharmacokinetic properties, as well as their affinity and specificity for PSMA. The therapeutic effect of radioligands was systematically evaluated in [¹⁷⁷Lu]Lu-Flu-1, [¹⁷⁷Lu]Lu-BWD, [¹⁷⁷Lu]Lu-P4-BWD, and [¹⁷⁷Lu]Lu-P4-PND. All PSMA ligands were of chemical purity >95%. The final radiochemical purity of the radioligands was achieved up to 99%. The cell-based and imaging study results showed that BWD had a high affinity for PSMA (IC₅₀ = 35.86 ± 0.56) and was significantly superior to the other radioligands in terms of tumor uptake and retention. The biodistribution study further confirmed that the tumor uptake of [¹⁷⁷Lu]Lu-BWD (64.28 ± 12.46%ID/g) was significantly higher than that of other [¹⁷⁷Lu]Lu-radioligands at 4 h postinjection, including [¹⁷⁷Lu]Lu-PSMA-617 (47.64 ± 11.39%ID/g). The TRT results showed that a single injection of 7.4 MBq of [¹⁷⁷Lu]Lu-BWD significantly inhibited the growth of PC3-PIP tumors, and it was superior to that of [¹⁷⁷Lu]Lu-PSMA-617 under the same conditions. [¹⁷⁷Lu]Lu-BWD with greatly enhanced tumor uptake and retention demonstrated remarkable therapeutic efficacy using significantly lower dosages for clinical translation to treat PCa with high level of PSMA expression.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264838","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":"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":"https://doi.org/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":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-10","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}