Pharmaceutical Research最新文献

{"title":"Pharmacological Innovations in Space: Challenges and Future Perspectives.","authors":"Zinnet Şevval Aksoyalp, Aybala Temel, Merve Karpuz","doi":"10.1007/s11095-024-03788-x","DOIUrl":"10.1007/s11095-024-03788-x","url":null,"abstract":"<p><strong>Purpose: </strong>Since the first human experience in space, the interest in space research and medicine to explore universe is growing day by day. The extreme space conditions mainly radiation and microgravity effects on human physiology, antimicrobial susceptibility, and efficacy, safety, and stability of drugs. Therefore, the aim of this review is to address the impact of extreme space conditions, mainly microgravity and radiation, on human physiology and highlights the need for future approaches by evaluating the effectiveness of strategies to prevent or mitigate health problems.</p><p><strong>Methods: </strong>Published papers and NASA technical documents were searched in Pubmed and Google Scholar databases using the keywords ''antimicrobial susceptibility or drug resistance or drug stability or innovations or pharmacokinetic or pharmacodynamics'' and ''radiation or microgravity or space environments or space medicine or space pharmacy'' to prepare this review.</p><p><strong>Results: </strong>In this review, the challenges regarding physiological effects and drug-related problems are examined through the evaluation of extreme conditions in space. Medications used in spaceflight are summarized, and the role of pharmacists specializing in space medicine is briefly explained. Last but not least, to overcome the aforementioned issues, novel approaches have been addressed, such as personalised treatments, development of space-resistant formulations and various microbial applications.</p><p><strong>Conclusions: </strong>Further research in the space medicine is required to facilitate the safe and healthy travel of humans to the Moon, Mars and other extraterrestrial destinations. One bear in mind that space research will contribute not only to the exploration of the universe, but also to the advancement of health and technological discoveries on Earth.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2095-2120"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623481","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 Current State of Biotransformation Science - Industry Survey of In Vitro and In Vivo Practices, Clinical Translation, and Future Trends.","authors":"John P Savaryn, Kevin Coe, Matthew A Cerny, Kevin Colizza, Patricia Moliner, Lloyd King, Bin Ma, Jim Atherton, Adam Auclair, Mark T Cancilla, Marsha Eno, Ulrik Jurva, Qin Yue, Sean Xiaochun Zhu, Elyse Freiberger, Guo Zhong, Ben Barlock, Jonny Nachtigall, Laurent Laboureur, Sandeepraj Pusalkar, Runcong Guo, Michael Niehues, Simon Hauri, Ester Tor Carreras, Christine Maurer, Chandra Prakash, Gary J Jenkins","doi":"10.1007/s11095-024-03787-y","DOIUrl":"10.1007/s11095-024-03787-y","url":null,"abstract":"<p><p>Embedded within the field of drug metabolism and pharmacokinetics (DMPK), biotransformation is a discipline that studies the origins, disposition, and structural identity of metabolites to provide a comprehensive safety assessment, including the assessment of exposure coverage in toxicological species. Spanning discovery and development, metabolite identification (metID) scientists employ various strategies and tools to address stage-specific questions aimed at guiding the maturation of early chemical matter into drug candidates. During this process, the identity of major (and minor) circulating human metabolites is ascertained to comply with the regulatory requirements such as the Metabolites in Safety Testing (MIST) guidance. Through the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), the \"Translatability of MetID In Vitro Systems Working Group\" was created within the Translational and ADME Sciences Leadership Group. The remit of this group was to objectively determine how accurate commonly employed in vitro systems have been with respect to prediction of circulating human metabolites, both qualitatively and quantitatively. A survey composed of 34 questions was conducted across 26 pharmaceutical companies to obtain a foundational understanding of current metID practices, preclinically and clinically, as well as to provide perspective on how successful these practices have been at predicting circulating human metabolites. The results of this survey are presented as an initial snapshot of current industry-based metID practices, including our perspective on how a harmonized framework for the conduct of in vitro metID studies could be established. Future perspectives from current practices to emerging advances with greater translational capability are also provided.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2079-2093"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576500","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 Update on Recent Drug Delivery Systems Targeting Brain Diseases via the Transnasal Pathway.","authors":"Huiying Zeng, Huangjie Lu, Jie Yang, Ping Hu","doi":"10.1007/s11095-024-03790-3","DOIUrl":"10.1007/s11095-024-03790-3","url":null,"abstract":"<p><strong>Objective: </strong>To explore the potential of transnasal drug delivery systems (DDS) as an effective means of bypassing the bloodbrain barrier (BBB) for enhanced central nervous system (CNS) targeting, aiming to improve therapeutic outcomes for CNS disorders while reducing systemic side effects.</p><p><strong>Methods: </strong>A review of current and emerging DDS technologies, including polymer nanoparticles, liposomes, and micelles, was conducted to assess their suitability for precision-targeted delivery to the brain through the transnasal route.</p><p><strong>Results: </strong>The investigated DDS demonstrate promising capabilities for CNS targeting via the nasal pathway, effectively preserving both the nasal mucosa and CNS integrity. These systems enhance drug precision within neural tissues, potentially improving therapeutic outcomes without harming adjacent tissues.</p><p><strong>Conclusions: </strong>Transnasal DDS offer a promising alternative to traditional delivery methods, with significant potential to advance the treatment of cerebrovascular diseases, neurodegenerative disorders, brain tumors, and psychiatric conditions. This approach represents an evolving frontier in neurotherapeutics, with the potential to transform CNS drug delivery practices.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2121-2141"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546708","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":"Development of 3D-Printed Two-Compartment Capsular Devices for Pulsatile Release of Peptide and Permeation Enhancer.","authors":"Pengchong Xu, Hanh Thuy Nguyen, Siyuan Huang, Huyen Tran","doi":"10.1007/s11095-024-03785-0","DOIUrl":"10.1007/s11095-024-03785-0","url":null,"abstract":"<p><strong>Objective: </strong>The oral absorption of a peptide is driven by a high local concentration of a permeation enhancer (PE) in the gastrointestinal tract. We hypothesized that a controlled release of both PE and peptide from a solid formulation, capable of maintaining an effective co-localized concentration of PE and peptide could enhance oral peptide absorption. In this study, we aimed to develop a 3D-printed two-compartment capsular device with controlled pulsatile release of peptide and sodium caprate (C10).</p><p><strong>Methods: </strong>3D-printed two-compartment capsular device was fabricated using a fused deposition modeling method. This device was then filled with LY peptide and C10. The release profile was modulated by changing the thickness and polymer type of the capsular device. USP apparatus II dissolution test was used to evaluate the impacts of device thickness and polymer selection on release profile in vitro. An optimal device was then enteric coated with HPMCAS.</p><p><strong>Results: </strong>A strong linear relationship between the thickness of capsular devices and the delay in the release onset time was observed. An increase in the device thickness or the use of PLA decreased the release rate. The capsular device with compartment 1, compartment 2 and fence thickness of 0.4; 0.95 and 0.5 mm, respectively, and the use of PVA achieved desired pulsatile release profiles of both peptide and C10. Furthermore, enteric-coated capsular devices with HPMCAS had similar pulsatile release profiles compared to non-enteric coated devices.</p><p><strong>Conclusion: </strong>These findings suggest potential application of 3D-printing techniques in the formulation development for complex modified drug release products.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2259-2270"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564647","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":"Pharmacokinetic Study of Fingolimod Nasal Films Administered via Nose-to-Brain Route in C57BL/6 J Mice as Potential Treatment for Multiple Sclerosis.","authors":"Paraskevi Papakyriakopoulou, Evangelos Balafas, Nikolaos Kostomitsopoulos, Dimitrios M Rekkas, Kumlesh K Dev, Georgia Valsami","doi":"10.1007/s11095-024-03745-8","DOIUrl":"10.1007/s11095-024-03745-8","url":null,"abstract":"<p><strong>Background: </strong>Fingolimod hydrochloride (FH) has emerged as a vital medication for managing Multiple Sclerosis (MS). Despite its high oral bioavailability of 93%, it is plagued by slow oral absorption (T_max = 8-12 h) and extensive hepatic metabolism. Intranasal administration has emerged as an alternative to address these limitations, ensuring efficient central nervous system delivery and minimizing peripheral exposure and first-pass metabolism.</p><p><strong>Objective: </strong>This study aims to develop and evaluate FH nasal films for enhanced drug delivery.</p><p><strong>Methods: </strong>A Design of Experiments approach was employed to formulate FH nasal films, utilizing HPMC E50 as a film-forming polymer, PEG 400 as a plasticizer, and Me-β-CD as a permeation enhancer. Two formulations with superior in vitro and ex vivo performance were selected for in vivo evaluation. A comparative pharmacokinetic study was conducted in C57BL/6 J mice in the brain and serum after administration of nasal films and oral FH solution, respectively. Sparse sampling and non-compartmental analysis were used.</p><p><strong>Results: </strong>FH nasal films efficiently delivered the drug to both serum (C_max(F3) = 0.35 ± 0.021, C_max(F4) = 0.38 ± 0.029 μg/mL) and brain (C_max(F3) = 0.39 ± 0.05, C_max(F4) = 0.44 ± 0.048 μg/mL), achieving higher levels than oral delivery. Brain relative bioavailability (% F_{rel (0-6 h)}) was 519% and 534%, while serum % F_{rel (0-6 h)} was 295% and 343%.</p><p><strong>Conclusions: </strong>The rapid nose-to-brain delivery within 30 min, in contrast to 10-h Tmax of the oral solution, indicates the potential of a combined IN and oral treatment regimen. This approach could expedite the attainment of steady-state concentrations, offering a promising method for managing multiple sclerosis (MS).</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1951-1963"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546709","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":"Molecular Dynamic Simulations Reveal that Water-Soluble QTY-Variants of Glutamate Transporters EAA1, EAA2 and EAA3 Retain the Conformational Characteristics of Native Transporters.","authors":"Alper Karagöl, Taner Karagöl, Shuguang Zhang","doi":"10.1007/s11095-024-03769-0","DOIUrl":"10.1007/s11095-024-03769-0","url":null,"abstract":"<p><strong>Objective: </strong>Glutamate transporters play a crucial role in neurotransmitter homeostasis, but studying their structure and function is challenging due to their membrane-bound nature. This study aims to investigate whether water-soluble QTY-variants of glutamate transporters EAA1, EAA2 and EAA3 retain the conformational characteristics and dynamics of native membrane-bound transporters.</p><p><strong>Methods: </strong>Molecular dynamics simulations and comparative genomics were used to analyze the structural dynamics of both native transporters and their QTY-variants. Native transporters were simulated in lipid bilayers, while QTY-variants were simulated in aqueous solution. Lipid distortions, relative solvent accessibilities, and conformational changes were examined. Evolutionary conservation profiles were correlated with structural dynamics. Statistical analyses included multivariate analysis to account for confounding variables.</p><p><strong>Results: </strong>QTY-variants exhibited similar residue-wise conformational dynamics to their native counterparts, with correlation coefficients of 0.73 and 0.56 for EAA1 and EAA3, respectively (p < 0.001). Hydrophobic interactions of native helices correlated with water interactions of QTY- helices (rs = 0.4753, p < 0.001 for EAA1). QTY-variants underwent conformational changes resembling the outward-to-inward transition of native transporters.</p><p><strong>Conclusions: </strong>Water-soluble QTY-variants retain key structural properties of native glutamate transporters and mimic aspects of native lipid interactions, including conformational flexibility. This research provides valuable insights into the conformational changes and molecular mechanisms of glutamate transport, potentially offering a new approach for studying membrane protein dynamics and drug interactions.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1965-1977"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of MicroRNA-124-3p in Breast Cancer Stem Cell Inhibition by Benzyl Isothiocyanate.","authors":"Su-Hyeong Kim, Shivendra V Singh","doi":"10.1007/s11095-024-03775-2","DOIUrl":"10.1007/s11095-024-03775-2","url":null,"abstract":"<p><strong>Purpose: </strong>We have shown previously that benzyl isothiocyanate (BITC) derived from cruciferous vegetables inhibits self-renewal of breast cancer stem-like cells (bCSC). The current study provides insights into the mechanism of bCSC inhibition by BITC.</p><p><strong>Methods: </strong>Quantitative real time-polymerase chain reaction and western blot analysis were performed to detect microRNAs (miRNAs) and Forkhead box Q1 (FoxQ1) protein expression, respectively. The bCSC were characterized by aldehyde dehydrogenase 1 activity and flow cytometric analysis of CD49f ^high/CD133^high fraction.</p><p><strong>Results: </strong>BITC treatment resulted in induction of miR-124-3p expression in MDA-MB-231 and MCF-7 cells. miR-124-3p did not affect BITC-mediated inhibition of cell migration or cell proliferation but it significantly regulated bCSC in response to BITC. We also found that miR-124-3p directly targets the 3'untranslated regions (UTR) of FoxQ1 and negatively regulates its expression. The BITC-mediated inhibition of bCSC was partially attenuated by miR-124-3p inhibitor.</p><p><strong>Conclusions: </strong>These findings indicate that miR-124-3p plays an important role in BITC-mediated inhibition of bCSC.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1921-1932"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392353","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":"Computational Modelling of the Impact of Evaporation on In-Vitro Dermal Absorption.","authors":"Benjamin N Deacon, Samadhi Silva, Guoping Lian, Marina Evans, Tao Chen","doi":"10.1007/s11095-024-03779-y","DOIUrl":"10.1007/s11095-024-03779-y","url":null,"abstract":"<p><strong>Purpose: </strong>Volatiles are common in personal care products and dermatological drugs. Determining the impact of evaporation of volatiles on skin permeation is crucial to evaluate and understand their delivery, bioavailability, efficacy and safety. We aim to develop an in-silico model to simulate the impact of evaporation on the dermal absorption of volatiles.</p><p><strong>Method: </strong>The evaporation of volatile permeants was modelled using vapour pressure as the main factor. This model considers evaporation as a passive diffusion process driven by the concentration gradient between the air-vehicle interface and the ambient environment. The evaporation model was then integrated with a previously published physiologically based pharmacokinetic (PBPK) model of skin permeation and compared with published in vitro permeation test data from the Cosmetics Europe ADME Task Force.</p><p><strong>Results: </strong>The evaporation-PBPK model shows improved predictions when evaporation is considered. In particular, good agreement has been obtained for the distributions in the evaporative loss, and the overall percutaneous absorption. The model is further compared with published in-silico models from the Cosmetics Europe ADME Task Force where favourable results are achieved.</p><p><strong>Conclusion: </strong>The evaporation of volatile permeants under finite dose in vitro permeation test conditions has been successfully predicted using a mechanistic model with the intrinsic volatility parameter vapour pressure. Integrating evaporation in PBPK modelling significantly improved the prediction of dermal delivery.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1979-1990"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Manufacturing Process and Compounding on Properties and Quality of Follow-On GLP-1 Polypeptide Drugs.","authors":"Morten Hach, Dorthe Kot Engelund, Simon Mysling, Jesper Emil Mogensen, Ole Schelde, Kim F Haselmann, Kasper Lamberth, Thomas Kvistgaard Vilhelmsen, Joan Malmstrøm, Kim Bonde Højlys-Larsen, Tina Secher Rasmussen, Jonas Borch-Jensen, Rasmus Worm Mortensen, Thomas Marker Thams Jensen, Julie Regitze Kesting, Andrei-Mircea Catarig, Désirée J Asgreen, Leif Christensen, Arne Staby","doi":"10.1007/s11095-024-03771-6","DOIUrl":"10.1007/s11095-024-03771-6","url":null,"abstract":"<p><strong>Purpose: </strong>The prevalence of follow-on and compounded products of glucagon-like peptide-1 analogs is increasing. We assessed glucagon-like peptide-1 analogs semaglutide and liraglutide for purity, potential immunogenicity, and expected stability, by comparing a representative selection of commercially available follow-on drug substances (DSs) and drug products (DPs) with their corresponding originators.</p><p><strong>Methods: </strong>Tests included several chromatography methods coupled with ultraviolet and mass spectrometry detectors, inductively coupled plasma optical emission spectroscopy, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, dissolution analyses, in silico peptide/major histocompatibility complex II-binding prediction, and fibrillation assays.</p><p><strong>Results: </strong>Overall, 16 injectable semaglutide, 8 oral semaglutide, and 2 injectable liraglutide follow-on products were analyzed alongside originator products. Compared with originator, follow-on injectable semaglutide DSs and DPs had new impurities and impurity patterns, including high molecular weight proteins, trace metals, anions, counterions, and residual solvents. Analyses showed that several commercialized follow-on oral semaglutide DPs had a markedly lower quantity of semaglutide than the label claim, while dissolution tests indicated different semaglutide and sodium N-(8-[2-hydroxybenzoyl] amino)caprylate (SNAC) release profiles, which may reduce bioavailability. Neoepitopes were identified in DS and DP semaglutide follow-ons, indicating potential immunogenicity. Fibrillation assays showed increased fibrillation tendency and reduced physical stability in liraglutide follow-on DP samples compared with originator.</p><p><strong>Conclusion: </strong>This study highlights that differences in the manufacturing processes of follow-on semaglutide and liraglutide (vs those used for originators) can result in several changes to the DSs and DPs. The impact of these changes on efficacy and safety outcomes remains unknown and should be investigated by clinical studies.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1991-2014"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392351","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":"Identification and Activity Study of an Impurity Band Observed in the nrSDS-PAGE of Aflibercept.","authors":"Meng Li, Weiyu Li, Xin Wang, Gang Wu, Jialiang Du, Gangling Xu, Maoqin Duan, Xiaojuan Yu, Chunbo Cui, Chunyu Liu, Zhihao Fu, Chuanfei Yu, Lan Wang","doi":"10.1007/s11095-024-03773-4","DOIUrl":"10.1007/s11095-024-03773-4","url":null,"abstract":"<p><strong>Background: </strong>Aflibercept is a biopharmaceutical targeting vascular endothelial growth factor (VEGF) that has shown promise in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in adults. Quality control studies of aflibercept employing non-reduced SDS-PAGE (nrSDS-PAGE) have shown that a significant variant band (IM1) is consistently present below the main band. Considering the quality control strategy of biopharmaceuticals, structural elucidation and functional studies are required.</p><p><strong>Methods: </strong>In this study, the variant bands in nrSDS-PAGE were collected through electroelution and identified by peptide mass fingerprinting based on liquid chromatography-tandem MS (LC-MS/MS). This variant was expressed using knob-into-hole (KIH) design transient transfection for the detection of ligand affinity, binding activity and biological activity.</p><p><strong>Results: </strong>The variant band was formed by C-terminal truncation at position N99 of one chain in the aflibercept homodimer. Then, this variant was successfully expressed using KIH design transient transfection. The ligand affinity of the IM1 truncated variant was reduced by 18-fold, and neither binding activity nor biological activity were detected.</p><p><strong>Conclusions: </strong>The efficacy of aflibercept is influenced by the loss of biological activity of the variant. Therefore, this study supports the development of a quality control strategy for aflibercept.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2031-2042"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351921","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}