Pharmaceutical Research最新文献

{"title":"Nano-DSF Technology as a Preliminary Decision-Making Tool for Long Term Stability Evaluation of Covid-19 Vaccine Antigens.","authors":"Rahul Misra, Siddhant Sharma, Manjit Haer, Jian Hu, Marina Kirkitadze, Przemek Kowal","doi":"10.1007/s11095-026-04097-1","DOIUrl":"https://doi.org/10.1007/s11095-026-04097-1","url":null,"abstract":"<p><strong>Purpose: </strong>Nano differential scanning fluorimetry (nano-DSF) is a high-throughput screening technique that simultaneously assesses colloidal and conformational stabilities of protein antigens by monitoring their thermal unfolding patterns and aggregation behaviors. It offers significant advantages over conventional approaches used for thermal stability assessment of proteins, such as Differential Scanning Calorimetry (DSC).</p><p><strong>Methods: </strong>The present study evaluates the thermal unfolding and aggregation behavior of an in-house recombinant COVID-19 SARS-CoV-2 spike protein variant and its engineered prototype as vaccine antigens. We investigated their structural integrity and colloidal behavior under well-defined physical conditions such as pH transition, addition of excipients, and at different manufacturing stages.</p><p><strong>Results: </strong>Changes in melting and aggregation temperatures (Tm and Tagg) were assessed as indicators of the structural integrity and colloidal stability of spike protein variants.</p><p><strong>Conclusion: </strong>We have shown how nano-DSF technology can be useful in developing a stable formulation which can minimize conformational changes and aggregation. Our study highlights the potential of nano-DSF for process optimization and as an advanced preliminary decision-making tool to be used before initiating long-term stability studies in biopharmaceutical R&D.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical Stability of Romiplostim: In-use Functional Study Using Microscale Thermophoresis New Strategy and Elisa.","authors":"Jesús Hermosilla, Salvador Casares-Atienza, Julio Ruiz-Travé, Anabel Torrente-López, Antonio Salmerón-García, Jose Cabeza, Natalia Navas","doi":"10.1007/s11095-026-04085-5","DOIUrl":"https://doi.org/10.1007/s11095-026-04085-5","url":null,"abstract":"<p><strong>Objective: </strong>Functional stability is crucial for therapeutic proteins at all stages of their lifecycle. Romiplostim (Nplate®) is world-wide used for treating immune thrombocytopenia purpura. Limited in-use stability data on the proper romiplostim handling is publicly available. This study aimed to evaluate romiplostin in-use functional stability focusing on the interaction with its therapeutic target (TPO-R) and to improve the existing functional assessment strategies by developing a new one using microscale thermophoresis (MST).</p><p><strong>Methods: </strong>Reconstituted romiplostim (Nplate®) samples were analysed. MST and ELISA functional methods were developed and optimized ad hoc to assess romiplostim functional stability. Far-UV-Circular-Dichroism and Intrinsic-Tryptophan-Fluorescence-Spectroscopy were used to ensure MST results by confirming the conformational stability of labelled TPO-R. In-use stability was assessed by subjecting romiplostim to conditions related to hospital handling, e.g. agitation and exposure to natural light; also, freezing and artificial light irradiation were checked as forced degraded condition.</p><p><strong>Results: </strong>MST and ELISA were described and validated by their figures of merit. Regarding romiplostim functional stability, both approaches yielded similar stability profiles, but MST detected subtle functional declines that were not revealed by ELISA. Furthermore, MST revealed insights into romiplostim binding stoichiometry, suggesting 1:2 interaction at high concentrations.</p><p><strong>Conclusion: </strong>Regarding functionality, romiplostim was particularly sensitive to light exposure, with less sensitivity to agitation and freezing. These findings also demonstrate that MST serves as new orthogonal strategy to ELISA for assessing functionality, even providing additional data on binding dynamics and stoichiometry. This new MST strategy is applicable for any type of functional study of therapeutic proteins.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Progress in Exosome-Derived Nanocarriers for Breast Cancer Therapy: Advances, Translational Barriers, and Scale-Up Considerations.","authors":"Julie R Youssef, Esraa M Elgammal, Dina M Mahdy, Noha F Ghazi, George Bebawy","doi":"10.1007/s11095-026-04095-3","DOIUrl":"https://doi.org/10.1007/s11095-026-04095-3","url":null,"abstract":"<p><p>Breast cancer remains the most prevalent malignancy among women worldwide and a major cause of cancer-related mortality. Despite remarkable progress in molecularly targeted and immune-based therapies, therapeutic resistance, dose-limiting systemic toxicity, and inefficient drug delivery continue to hinder clinical outcomes, particularly in aggressive subtypes such as triple-negative breast cancer. Exosomes, naturally secreted nanosized vesicles, have emerged as a transformative platform owing to their biocompatibility, intrinsic targeting capability, and ability to transport diverse therapeutic cargos across biological barriers. Recent advances in exosome biology, engineering, and isolation technologies have reignited interest in their clinical exploitation as drug delivery systems. However, translation into clinical oncology remains in its early stages. This review provides a comprehensive overview of exosome-based drug delivery systems specifically within the context of breast cancer therapy, critically evaluating their sources, isolation techniques, cargo loading strategies, targeting mechanisms, and formulation considerations. It also examines preclinical findings demonstrating enhanced therapeutic efficacy and reduced off-target toxicity, alongside the limited yet growing number of clinical trials investigating exosome therapeutics in solid tumours. Importantly, the review identifies major gaps, including lack of standardized manufacturing protocols, incomplete pharmacokinetic understanding, and unresolved safety concerns, that currently impede clinical translation. By bridging molecular insights with translational perspectives, this work underscores the untapped potential of exosomes as next-generation drug carriers in breast cancer. It highlights the urgent need for harmonized methodologies, scalable production systems, and regulatory frameworks to enable their safe and effective integration into future cancer therapeutics.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Use of Digital Image Processing in the Modelling of a Roller Compaction Milling Operation.","authors":"David Wilson, Alexa Mesham, Felix Tim Bölle","doi":"10.1007/s11095-026-04101-8","DOIUrl":"https://doi.org/10.1007/s11095-026-04101-8","url":null,"abstract":"<p><strong>Purpose: </strong>Granulation by roller compaction is an important unit operation in the production of pharmaceutical oral solid dosages. This process involves producing a densified \"ribbon\" of compressed powder between two counter rotating rolls that is then feed into a screening type mill and particulate matter of the order of 1-2 mm is produced. In roller compaction, rate of production is generally maximised by increasing the roll speed, thus increasing the rate of ribbon production. However, such increases in production could result in issues with ribbon milling, potentially causing the mill to become overwhelmed. Knowledge of important milling parameters such as mill residence time and steady state hold up value as a function of roll and mill speed would allow for this parameter to be scaled. Traditional experiments towards this objective are problematic.</p><p><strong>Methods: </strong>Presented here is a digital image processing approach that allows the continual monitoring of the mass of powder within a roller compactor's mill utilising the equipment's observation window. This allowed for an assessment of steady state mass hold up and the mean residence time in the mill. In this study, mean residence times were calculated to be between 45 and 120 s.</p><p><strong>Results: </strong>The approach allowed for the rapid accumulation of data sufficient to construct a, data driven model predicting both residence time and steady state hold up as a function of both roll speed and mill speed.</p><p><strong>Conclusion: </strong>It is the authors assertion that this kind of image processing approach, has great utility in pharmaceutical manufacturing.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bio-inspired White Tablet Coating Film Without Titanium Dioxide.","authors":"Yutong Tian, Shihao Song, Yaojie Shi, Li Yuan, Jiaqi Yan, Da Wang, Luping Sha, Li Yang","doi":"10.1007/s11095-026-04102-7","DOIUrl":"https://doi.org/10.1007/s11095-026-04102-7","url":null,"abstract":"<p><strong>Background: </strong>Titanium dioxide (TiO₂) is widely used as a white additive in food and pharmaceuticals, but its safety has raised increasing concerns. Currently, calcium carbonate is commonly used as an alternative to TiO₂ in white film coatings, although it provides inferior whiteness. With the development of the health industry, TiO₂-free and pigment-free white tablet coatings are becoming more desirable.</p><p><strong>Methods: </strong>Inspired by white beetle scales, porous films were fabricated via phase separation between polyvinyl alcohol (PVA) and polyethylene glycol (PEG). The refractive index difference between polymer and air generated strong light scattering. Light-shielding effect of calcium carbonate of different morphologies was further investigated.</p><p><strong>Results: </strong>Under the same type of calcium carbonate as the opacifier, porous PVA/PEG films showed CIELab whiteness all above 80 (up to 87), much higher than the dense films using lipid plasticizers. With the same porous structure, quasi-rhombohedral calcium carbonate increased whiteness by 8.2% compared with spindle aggregates.</p><p><strong>Conclusions: </strong>Porous structures dominated whiteness improvement. Bioinspired porous films via polymer-polymer phase separation represented a novel strategy for TiO₂-free white tablet coating, and could guide the screening of other phase-separating polymers to further improve the film whiteness and properties.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Cyclodextrins in Modulating Stimuli-Responsiveness for Anticancer Drug Delivery.","authors":"Andrea Cesari, Liu Zhengming, Fabio Bellina","doi":"10.1007/s11095-026-04096-2","DOIUrl":"https://doi.org/10.1007/s11095-026-04096-2","url":null,"abstract":"<p><strong>Background: </strong>The precision delivery of active pharmaceutical ingredients remains a major challenge in modern pharmacology, where conventional therapies often lack selectivity and cause severe side effects. Stimuli-responsive drug delivery systems (SRDDS) represent a promising strategy to achieve controlled release in response to pathological microenvironments or external triggers. While various organic and inorganic carriers have been investigated, cyclodextrins (CDs) occupy a unique position due to their biocompatibility, safety record, and distinctive molecular architecture. Beyond their established role as solubilizing excipients, CDs can act as a fundamental component capable of driving responsiveness within drug delivery systems.</p><p><strong>Objective: </strong>This review highlights cyclodextrin-based stimuli-responsive systems (SRCDS) in which CDs themselves mediate responsiveness, rather than serving as simple structural elements.</p><p><strong>Scope and focus: </strong>A comparative discussion of different responsive mechanisms is provided, offering insights into the design principles that may accelerate the clinical translation of CD-based SRDDS. A particular focus will be provided to chemical structure components exerting stimuli responsiveness. In addition, recent publications on SRCDS with pharmacological or biological experimental investigations and relevance are reviewed, with particular attention to applications in cancer therapy.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Particle Properties on High Concentration Suspension Performance and Stability of Spray-Dried Monoclonal Antibodies.","authors":"Yijing Huang, Jiaying Liu, Ruomeng Qiu, Kaizhu Guo, Abby Devlin, Ashlesha Raut","doi":"10.1007/s11095-026-04083-7","DOIUrl":"https://doi.org/10.1007/s11095-026-04083-7","url":null,"abstract":"<p><strong>Objective: </strong>Subcutaneous (subQ) administration of biologic drug products is increasingly preferred to enable patient self-administration and reduce healthcare burden. However, the small dosing volume for subQ delivery necessitates high-concentration formulations, which often suffer from elevated viscosity and physical instability, creating challenges in manufacturing, injectability, and storage. Spray drying has emerged as a versatile particle engineering technique to produce solid biologic powders that can be redispersed into suspensions. While suspensions of spray-dried particles have shown promise in reducing viscosity compared to liquid solutions, the influence of biologic particle properties on suspension performance remains poorly understood. This study aimed to elucidate how particle size and surface characteristics affect viscosity and stability of high-concentration monoclonal antibody (mAb) suspensions.</p><p><strong>Methods: </strong>Spray-dried mAb particles were prepared with varied sizes and leucine addition. Suspensions were evaluated for viscosity, injectability through 27G needles, sedimentation, physical, chemical and structural stability during storage at 5°C and 25°C for 3 months and at 40°C for 1 month.</p><p><strong>Results: </strong>Larger particle size, less surface dimpling and leucine addition significantly reduced viscosity without compromising physical and chemical stability; no sedimentation was observed. All suspensions were injectable via 27G needles. No notable aggregation or fragmentation occurred under tested conditions.</p><p><strong>Conclusion: </strong>Particle size and surface properties modulate suspension viscosity but do not impact stability. Particle engineering through spray drying represents an effective approach to enable high-concentration biologic suspensions for subQ delivery.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Versatile Role of GDF5 in Chondrogenic Progenitor Cell-mediated Cartilage Regeneration via a Hyaluronic Acid-fibrin IPN Hydrogel Platform.","authors":"Rui He, Venkateswaran Ganesh, Pornpoj Phruttiwanichakun, James A Martin, Dongrim Seol, Aliasger K Salem","doi":"10.1007/s11095-026-04079-3","DOIUrl":"https://doi.org/10.1007/s11095-026-04079-3","url":null,"abstract":"<p><strong>Objective: </strong>Focal damage to articular cartilage incurred during joint injuries frequently progresses to post-traumatic osteoarthritis (PTOA) due to the limited intrinsic repair capacity of cartilage. Chondrogenic progenitor cells (CPCs) residing within the cartilage can contribute to repair if effectively recruited and activated. Early interventions that enhance CPC homing and their subsequent chondrogenesis offer a regenerative strategy to prevent PTOA progression, addressing the current lack of effective early clinical therapies. GDF5 stands out as a key protein involved in cartilage development, yet its potential to mobilize CPC-mediated regeneration remains underexplored.</p><p><strong>Methods: </strong>We evaluated the effects of GDF5 on CPC migration, proliferation, chondrogenic differentiation, and anti-catabolic activity using in vitro CPC models. To assess CPC chemotaxis in a clinically relevant biomaterial context, GDF5 was incorporated into a hyaluronic acid/fibrin interpenetrating network (IPN) hydrogel and tested in an ex vivo cartilage defect model.</p><p><strong>Results: </strong>GDF5 acted as a potent chemoattractant for CPCs, promoting their recruitment toward cartilage defects when delivered via a hyaluronic acid/fibrin IPN hydrogel in an ex vivo model. GDF5 also enhanced CPC proliferation, consistent with activation of a glycolysis-associated transcriptional program. In addition, GDF5 significantly upregulated chondrogenic markers, including SOX9, COL2a1, and ACAN, and elevated extracellular matrix components in CPCs, potentially through activation of the PI3K/AKT signaling pathway. Furthermore, GDF5 reduced expression of a key catabolic enzyme ADAMTS5, possibly through the WWP2/miR-140 axis.</p><p><strong>Conclusion: </strong>These findings highlight the versatile role of GDF5 on endogenous CPCs. When combined with a hydrogel platform, GDF5 may serve as an early therapeutic strategy to convert injured cartilage from a passive site of degeneration into one of active regeneration.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Chemoprevention of Colon Carcinogenesis by Oleanolic Acid and Its Analog in Male F344 Rats and Modulation of COX-2 and Apoptosis in Human Colon HT-29 Cancer Cells.","authors":"Naveena B Janakiram, Cooma Indranie, Swamy V Malisetty, Patlolla Jagan, Vernon E Steele, Chinthalapally V Rao","doi":"10.1007/s11095-026-04090-8","DOIUrl":"https://doi.org/10.1007/s11095-026-04090-8","url":null,"abstract":"","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Innovative Multifaceted Approach to Enhance the Sensitivity of a Target Engagement ELISA.","authors":"Nahong Qiu, Alexandra Nitsche, Isabelle Beley, Alessio Maiolica, Jennifer Cunliffe, Julie De Gagné","doi":"10.1007/s11095-025-04003-1","DOIUrl":"https://doi.org/10.1007/s11095-025-04003-1","url":null,"abstract":"<p><p>Target engagement (TE) assessments often come with bioanalytical challenges, particularly with low baseline level targets like cytokines and chemokines. Commercial immunoassay kits often cannot meet the requirements of sensitivity and drug interference. We present a novel methodology that significantly enhances the sensitivity of a conventional sandwich enzyme-linked immunosorbent assay (ELISA) for TE assessment. To increase sensitivity, various strategies were applied, including the combined use of U-bottomed assay plates and Intelligent Multifunctional Analytical Plates (IMAPlate™). Lowering volumes of enzyme substrate and stop solution in U-bottomed plate led to a concentrated color solution. The unique bottom-less \"well\" of the IMAPlate™ was utilized to measure the intensified color solution, resulting in a significantly magnified signal. The use of Pluronic^® F-127 detergent into the assay buffer system helped reduce assay background while improving sensitivity. The biotin labeling process of the detection antibody was optimized and combined with using poly horseradish-peroxidase (HRP)-streptavidin to further enhance sensitivity. To evaluate this approach, we developed a sandwich ELISA to quantify total (free and drug bound) serum human interleukin-13 (IL-13). A pair of non-competing for target binding antibodies was used. Due to IL-13's small size, steric hindrance was observed in the presence of NVS-0031 (anti-IL-13 mAb) and a saturation method to mitigate this interference was implemented. Despite an initial 40% sensitivity loss, we eventually improved sensitivity approximately 200-fold to achieve a limit of quantitation of 0.05 pg/mL. This methodology has been effectively employed in other ELISA-based bioanalytical assays that require heightened sensitivity (data not shown), demonstrating its wide-ranging applicability.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}