Journal of pharmaceutical sciences最新文献_第3页

Protein-bound cisplatin could exhibit an efficient antitumor effect in vivo 蛋白结合的顺铂在体内表现出有效的抗肿瘤作用

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-06-17 DOI: 10.1016/j.xphs.2025.103881

Nana Cristina Amorim Matsuo , Hidenori Ando , Haruka Takata , Tatsuhiro Ishida

{"title":"Protein-bound cisplatin could exhibit an efficient antitumor effect in vivo","authors":"Nana Cristina Amorim Matsuo , Hidenori Ando , Haruka Takata , Tatsuhiro Ishida","doi":"10.1016/j.xphs.2025.103881","DOIUrl":"10.1016/j.xphs.2025.103881","url":null,"abstract":"<div><div>Cisplatin has been a mainstay in the treatment of various cancers, and continues to be one of the most effective and essential drugs for cancer treatment. However, the severe nephrotoxicity induced by cisplatin continues to be problematic in clinical settings. Following intravenous (<em>i.v.</em>) injection, cisplatin binds to serum proteins in blood circulation. Also, the contributions that protein-bound cisplatin confers to both the antitumor and adverse effects remain uncertain. In this study, therefore, we performed pharmacokinetic and pharmacological studies of protein-bound cisplatin. Following <em>i.v.</em> injection, protein-bound cisplatin was retained in blood circulation much longer than free-form cisplatin. The protein-bound cisplatin caused no renal toxicities, while equivalent doses of free-form cisplatin did produce this negative effect. In antitumor studies, surprisingly, sequential <em>i.v.</em> treatments with protein-bound cisplatin clearly suppressed tumor growth to an extent that was comparable to the same doses of free-form cisplatin both in the treatment of murine B16F10 melanoma as well as in that for human A2780 ovarian tumor-bearing mice. These results suggest that the protein-bound form partially contributes to the therapeutic outcome of <em>i.v.</em>-injected cisplatin for cancer treatments. Also, protein-bound cisplatin could become a novel anticancer agent to suppress tumor growth with less renal toxicity.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103881"},"PeriodicalIF":3.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335744","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}

引用次数: 0

Sustained release of betamethasone from solid lipid nanoparticles loaded polymeric hydrogels with natural emollient: One step closer to effective topical therapy for atopic dermatitis 固体脂质纳米颗粒负载天然润肤剂的聚合水凝胶中倍他米松的持续释放：离特应性皮炎的有效局部治疗又近了一步。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-06-16 DOI: 10.1016/j.xphs.2025.103876

Tejas Mahesh Athavale , Maddhusja Nalliah , Sybil Obuobi , Øystein Grimstad , Nataša Škalko-Basnet

{"title":"Sustained release of betamethasone from solid lipid nanoparticles loaded polymeric hydrogels with natural emollient: One step closer to effective topical therapy for atopic dermatitis","authors":"Tejas Mahesh Athavale , Maddhusja Nalliah , Sybil Obuobi , Øystein Grimstad , Nataša Škalko-Basnet","doi":"10.1016/j.xphs.2025.103876","DOIUrl":"10.1016/j.xphs.2025.103876","url":null,"abstract":"<div><div>Atopic dermatitis (AD), an inflammatory skin disease, has persisted as a global burden for decades. The existing therapy lacks multitargeted formulations, is ineffective, and bears adverse effects. Consequently, it offers limited relief from pruritus and inflammation, impacting both the patients’ quality of life as well as health care systems. We hypothesize that localized therapy comprising natural emollients offers better therapeutic outcome and superior acceptability. Herewith, we propose the novel hydrogel formulations for multipurpose treatment that utilizes lipid nanoparticles with model drug betamethasone dipropionate (BMS), that are incorporated in gel formulation comprising a natural emollient, coconut oil. BMS-solid lipid nanoparticles (BMS-SLNs), optimized for size and drug load, were embedded in three different hydrogels, all comprising coconut oil as an emollient. Chitosan, alginate, and carbomer were selected as hydrogel-forming material. The nanocarriers-in-hydrogel formulations were evaluated through BMS permeation in human skin as well as their physicochemical properties including viscosity, stability, texture, rheology and pH. Preliminary <em>in vitro</em> and <em>ex vivo</em> studies demonstrated that all hydrogel formulations prolonged BMS release up to 24 h. All formulations were found to be safe as confirmed by <em>in vitro</em> cytotoxicity assay. The novel nanocarrier-in-hydrogel formulations hold promise as an effective therapeutic strategy for AD management.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103876"},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293931","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}

引用次数: 0

Current and emerging strategies for subcutaneous delivery of high-concentration and high-dose antibody therapeutics 目前和新兴的策略皮下递送高浓度和高剂量抗体治疗。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-06-16 DOI: 10.1016/j.xphs.2025.103877

Steven Ren

{"title":"Current and emerging strategies for subcutaneous delivery of high-concentration and high-dose antibody therapeutics","authors":"Steven Ren","doi":"10.1016/j.xphs.2025.103877","DOIUrl":"10.1016/j.xphs.2025.103877","url":null,"abstract":"<div><div>Subcutaneous (SC) administration of monoclonal antibodies (mAbs) offers patient-centric benefits such as self-administration, fewer hospital visits, and cost savings. However, developing high-concentration formulations (HCFs, ≥ 100 mg/mL) for SC delivery presents challenges, particularly high viscosity, which affects manufacturability and injectability. This review examines the molecular basis of viscosity in highly concentrated antibody solutions, highlighting the roles of electrostatic and hydrophobic interactions. Key formulation factors, including pH, buffers, sugars, surfactants, and ionic strength are systematically analyzed for their impact on viscosity of antibody solutions. Computational and high-throughput screening tools, including machine learning and biophysical parameters, are explored for early-stage viscosity prediction and candidate selection. Viscosity reduction strategies, including approved and emerging viscosity-reducing agents (VRA) and their synergistic combinations, are comprehensively reviewed. Alternative SC delivery approaches for high-dose antibody therapeutics, such as maximized injection volume, prefilled syringes equipped with shorter ultra-thin wall (UTW) needles or tapered needles, multiple injections per dose, wearable devices, and co-formulation with hyaluronidase, are outlined. Additionally, novel technologies like non-aqueous powder suspensions and large-volume handheld autoinjectors (AI) are discussed, though further development is needed to address usability, bioavailability, and safety concerns. By integrating computational tools, high-throughput screening, diverse viscosity reduction strategies, and alternative delivery solutions, this review provides a structured framework for overcoming high-viscosity and high-dose challenges, facilitating the development of patient-friendly antibody therapeutics for SC administration.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103877"},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293916","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}

引用次数: 0

Improved identification of host cell proteins in monoclonal antibodies by combining filter-aided sample preparation and native digestion 结合过滤辅助样品制备和天然消化技术改进单克隆抗体中宿主细胞蛋白的鉴定。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-06-15 DOI: 10.1016/j.xphs.2025.103875

Yang Yang , Jing Wu , Fang Wang, Mark Lefers

{"title":"Improved identification of host cell proteins in monoclonal antibodies by combining filter-aided sample preparation and native digestion","authors":"Yang Yang , Jing Wu , Fang Wang, Mark Lefers","doi":"10.1016/j.xphs.2025.103875","DOIUrl":"10.1016/j.xphs.2025.103875","url":null,"abstract":"<div><div>Host cell proteins (HCPs) in biotherapeutics can present potential safety risks or compromise product stability at trace levels. Therefore, removal, testing, and characterization of HCPs are critical throughout biotherapeutic process development. While enzyme-linked immunosorbent assay (ELISA) is the gold standard for quantifying HCPs, it does not provide information on HCP identity. As a result, HCP analysis by liquid chromatography-mass spectrometry (LC-MS) has gained prominence for its ability to identifying HCPs. However, compared to ELISA’s parts-per-billion sensitivity, LC-MS is limited by its dynamic range, often unable to cover magnitude difference between HCP and biotherapeutic concentrations. Thus, an effective HCP enrichment method is highly desirable. In this study, we propose a new strategy for HCP identification that combines filter-aided sample preparation (FASP) with native digestion, followed by shotgun proteomics analysis. This approach improves mAb removal compared to standard native digestion, enabling greater HCP enrichment and identification. Our method detects all spiked proteins at 1 ppm and most at 0.5 ppm, ranging from 12 to 470 kDa, demonstrating broad molecular weight coverage of HCPs. A proof-of-concept analysis using the NISTmAb standard demonstrates that our filter-aided native digestion identifies 155 more HCPs than the standard native digestion. When applying this strategy to an in-house antibody with low amounts of HCPs, we can quantify HCPs at levels as low as 0.03 ppm, demonstrating the high sensitivity in HCP characterization.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103875"},"PeriodicalIF":3.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317176","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}

引用次数: 0

Thermal analysis and FTIR in supplier qualification: Evidence of impurities and risks associated with handling 供应商鉴定中的热分析和红外光谱：杂质和处理相关风险的证据。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-06-15 DOI: 10.1016/j.xphs.2025.103880

Áquila Priscilla Ferreira de Mendonça, Alana Mara Calou de Araújo, Linaldo Francisco da Silva Filho, Ellen Oliveira da Trindade, José Lourenço de Freitas Neto, Antônio Rodolfo de Faria, Amanda Carla Quintas de Medeiros Vieira, Laís Felix de Queiroz Ferreira, Débora Vitória Firmino de Lima, Pedro José Rolim Neto, Maria José Cristiane Lima e Silva, Rosali Maria Ferreira da Silva

{"title":"Thermal analysis and FTIR in supplier qualification: Evidence of impurities and risks associated with handling","authors":"Áquila Priscilla Ferreira de Mendonça, Alana Mara Calou de Araújo, Linaldo Francisco da Silva Filho, Ellen Oliveira da Trindade, José Lourenço de Freitas Neto, Antônio Rodolfo de Faria, Amanda Carla Quintas de Medeiros Vieira, Laís Felix de Queiroz Ferreira, Débora Vitória Firmino de Lima, Pedro José Rolim Neto, Maria José Cristiane Lima e Silva, Rosali Maria Ferreira da Silva","doi":"10.1016/j.xphs.2025.103880","DOIUrl":"10.1016/j.xphs.2025.103880","url":null,"abstract":"<div><div>Magistral formulations allow for dose customization according to patient needs. The qualification of raw material suppliers is essential to ensure the efficacy and safety of the final product. Despite regulations, deviations, losses, and contamination may occur during the process. Thus, this study analyzed supplier qualification, highlighting the importance of characterization tests to ensure high-quality raw materials and, consequently, good pharmaceutical products. Four raw materials commonly used in compounding pharmacies were evaluated: hyaluronic acid, ketoconazole, hydroquinone, and papain, all susceptible to changes caused by factors such as temperature, humidity, and light. Samples were obtained from two compounding pharmacies in Recife, Brazil, between February and March 2024. The characterization tests included Differential Scanning Calorimetry, Thermogravimetric Analysis, and Fourier Transform Infrared Spectroscopy. The results showed impurities in some samples, especially those of papain, indicating structural modifications. On the other hand, the samples of hyaluronic acid, ketoconazole, and hydroquinone showed adequate purity. Therefore, it is essential to perform physicochemical control of active pharmaceutical ingredients intended for compounding to confirm their respective purities and ensure the safety and efficacy of the medications produced, ultimately safeguarding patient health.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103880"},"PeriodicalIF":3.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317177","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}

引用次数: 0

Predictive stability in biopharmaceuticals and vaccines: perspectives and recommendations towards accelerating patient access 生物制药和疫苗的预测稳定性：加速患者获得的观点和建议。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-06-13 DOI: 10.1016/j.xphs.2025.103873

Daniel Skomski , Andrea Ji , Drago Kuzman , Didier Clenet , Aaron Hieb , Scott W Roberts , Joe Berry , Christopher Lentes , Jos Weusten , Kirsten MacArthur , Amy St. Charles , Ben Ahlstrom , Sandra Auguste-Bowler , Leanne Chinn , Armin Boehrer , Shaoxin Feng , Chris Thompson , Bernard Francq , Christian Laue , Marie-Eve Bury , Declan Lowney

{"title":"Predictive stability in biopharmaceuticals and vaccines: perspectives and recommendations towards accelerating patient access","authors":"Daniel Skomski , Andrea Ji , Drago Kuzman , Didier Clenet , Aaron Hieb , Scott W Roberts , Joe Berry , Christopher Lentes , Jos Weusten , Kirsten MacArthur , Amy St. Charles , Ben Ahlstrom , Sandra Auguste-Bowler , Leanne Chinn , Armin Boehrer , Shaoxin Feng , Chris Thompson , Bernard Francq , Christian Laue , Marie-Eve Bury , Declan Lowney","doi":"10.1016/j.xphs.2025.103873","DOIUrl":"10.1016/j.xphs.2025.103873","url":null,"abstract":"<div><div>The perspective review discusses predictive stability computational modeling and scientific risk-based approaches to prospectively assess long-term stability and shelf-life of biotherapeutics and vaccines. New regulatory approaches are considered in the context of evolving industry guidelines which are expected to lead to increased usage in clinical trials and market applications. Case studies for many critical quality attributes are broadly covered. Model methodologies, complexities, and mitigations, as well as emerging technologies, are also explained. Outputs of an industry-wide survey elucidate how biopharmaceutical companies are navigating this changing environment. Altogether, it is suggested that predictive stability holds promise for accelerating patient access to new medicines by overcoming stability-related bottlenecks while further enhancing scientific understanding and product robustness.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103873"},"PeriodicalIF":3.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293930","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}

引用次数: 0

Design and in vitro evaluation of thiolated alginates with N-acetyl-L-cysteine/L-cysteine substructures 具有n -乙酰- l-半胱氨酸/ l-半胱氨酸亚结构的硫代海藻酸盐的设计和体外评价。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-06-12 DOI: 10.1016/j.xphs.2025.103872

Laura Mackaya-Navarro , Patrick Knoll , Víctor H. Campos-Requena , Paulina I. Hidalgo , Andreas Bernkop-Schnürch

{"title":"Design and in vitro evaluation of thiolated alginates with N-acetyl-L-cysteine/L-cysteine substructures","authors":"Laura Mackaya-Navarro , Patrick Knoll , Víctor H. Campos-Requena , Paulina I. Hidalgo , Andreas Bernkop-Schnürch","doi":"10.1016/j.xphs.2025.103872","DOIUrl":"10.1016/j.xphs.2025.103872","url":null,"abstract":"<div><div>A new generation S-protected thiolated alginate was synthesized using a ligand based on l-cysteine protected with <em>N</em>-acetyl-l-cysteine (NACys-Cys) in order to obtain a thiomer with improved mucoadhesive properties. Two types of alginate with different molar mass were evaluated with two ligand concentrations. The successful protection with NACys-Cys was confirmed with FT-IR, NMR and free amino group quantification. Quantification of disulfide and thiol groups showed a maximum of 546.93 ± 58.27 µmol S–S/g polymer and 35.48 ± 1.79 µmol –SH/g polymer. Evaluation of swelling behavior showed a ∼5-fold increase in weight at 2 h in buffer pH 6.8. <em>Ex vivo</em> mucoadhesion tests were performed with porcine intestinal mucosa where the S-protected thiomers remained adhered for an average of 70.9 ± 7.0 h, which was ∼15-fold longer than unmodified alginate (<em>p</em> < 0.0001). Cytotoxicity of S-protected thiomers was evaluated on human colorectal carcinoma cells (Caco-2) by resazurin assay. Both unmodified polymer and thiomers did not show a significant decrease in cell viability (<em>p</em> > 0.05). The results indicate that this novel third-generation S-protected thiomer provides remarkable <em>ex vivo</em> mucoadhesive properties, adequate swelling capacity and no <em>in vitro</em> cytotoxicity. According to results it might be a promising material for medical and pharmaceutical applications.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103872"},"PeriodicalIF":3.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293917","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}

引用次数: 0

Particle size distribution resolution limit of AAV hs-SV-AUC relative to ls-SV-AUC, mass photometry, and charge-detection mass spectrometry AAV - hs-SV-AUC相对于ls-SV-AUC、质光度法和电荷检测质谱法的粒径分布分辨率极限。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-06-12 DOI: 10.1016/j.xphs.2025.103878

Bashkim Kokona , Austin Vogt , Neal Whitaker , Aubree O’Neill , Kevin D. Ausman , Jin Wen , Alfredo Lopez De Leon , Kimberly A. Malecka , Thomas A. Laue , Steven A. Berkowitz , Sambit R. Kar

{"title":"Particle size distribution resolution limit of AAV hs-SV-AUC relative to ls-SV-AUC, mass photometry, and charge-detection mass spectrometry","authors":"Bashkim Kokona , Austin Vogt , Neal Whitaker , Aubree O’Neill , Kevin D. Ausman , Jin Wen , Alfredo Lopez De Leon , Kimberly A. Malecka , Thomas A. Laue , Steven A. Berkowitz , Sambit R. Kar","doi":"10.1016/j.xphs.2025.103878","DOIUrl":"10.1016/j.xphs.2025.103878","url":null,"abstract":"<div><div>Precise and accurate particle size distributions (PSD) of adeno-associated virus (AAV) preparations are an important measure of sample quality. Particularly challenging is the quantitation of AAV particles carrying genetic payload variants, which are considered impurities that must be minimized. While a plethora of methods exist to evaluate the amount of empty and full AAV particles, quantitation of partially-filled capsids having genomes close to the size of full capsids, has proven more challenging. The recently developed high-speed sedimentation velocity protocol (hs-SV-AUC) provides precise and accurate PSDs quickly. Here we assess the limiting resolution of hs-SV-AUC using both simulated and experimental data for a 1:1 mixture of two purified AAV preparations differing in DNA payloads by 696 nucleotides (NT). As few as 12 absorbance scans are needed to achieve baseline resolution of the two AAV components, while also providing AAV composition information via dual-wavelength analysis. For comparison, PSDs were obtained for the same 1:1 AAV mix using low-speed SV-AUC (ls-SV-AUC), mass photometry (MP) and charge detection mass spectrometry (CD-MS). In terms of their ability to separate the two full AAV peaks, the order of resolution of these methods is as follows: hs-SV-AUC > CD-MS > MP ≈ ls-SV-AUC. The advantages and disadvantages of each method are discussed.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103878"},"PeriodicalIF":3.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293918","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}

引用次数: 0

Topological indices and data analysis techniques modeling to predict the physicochemical properties of tetracycline antibiotics 拓扑指数和数据分析技术建模预测四环素类抗生素的理化性质。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-06-10 DOI: 10.1016/j.xphs.2025.103871

Fateme Movahedi , Mahsa Zameni , Mohammad Hadi Akhbari , Mohammad Hassan Shahavi , Saeid Rajabnezhad

{"title":"Topological indices and data analysis techniques modeling to predict the physicochemical properties of tetracycline antibiotics","authors":"Fateme Movahedi , Mahsa Zameni , Mohammad Hadi Akhbari , Mohammad Hassan Shahavi , Saeid Rajabnezhad","doi":"10.1016/j.xphs.2025.103871","DOIUrl":"10.1016/j.xphs.2025.103871","url":null,"abstract":"<div><div>The tetracycline family of drugs is one of the most widely used groups of antibiotics in modern medicine. Topological indices act as a bridge between chemistry and mathematics. The Quantitative Structure-Property Relationship (QSPR) models utilize the molecular structure of compounds to predict the physicochemical properties. In this paper, a computational approach was performed using MATLAB coding and decoding to calculate the Sombor-type topological indices of this group of drugs. The linear regression approach has been used in the quantitative model of structure-property relationships to investigate the relationships between Sombor indices and physicochemical properties. This investigation aims to examine the efficacy of topological indices of the Sombor type in predicting the physicochemical properties of tetracycline numerically. The linear regression analysis concluded that the best predictor for H-bond donors, H-bond acceptors, rotatable bonds, and polar surface area is the modified reduced Sombor index, and the increased Sombor index is effective for polarizability and molecular weight. Furthermore, the best predictor of topological indices for refractivity is the Sombor index.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103871"},"PeriodicalIF":3.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285003","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}

引用次数: 0

Immunogenicity risk mitigation of therapeutic proteins with translational immunogenicity, analytical characterization, and regulatory insight. 免疫原性风险降低与翻译免疫原性治疗蛋白，分析表征，和调控的见解。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-06-08 DOI: 10.1016/j.xphs.2025.103870

Sadiqua Shadbar, Sathy Balu Iyer, Jared Auclair, Daniel Dadon

{"title":"Immunogenicity risk mitigation of therapeutic proteins with translational immunogenicity, analytical characterization, and regulatory insight.","authors":"Sadiqua Shadbar, Sathy Balu Iyer, Jared Auclair, Daniel Dadon","doi":"10.1016/j.xphs.2025.103870","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103870","url":null,"abstract":"<p><p>The immunogenicity of therapeutic proteins remains a key challenge, leading to early and late-stage clinical failures, posing a significant hurdle in the development of safe and efficacious biopharmaceuticals. This review highlights the main categories of factors influencing the immune response-mediated impacts of biotherapeutics: 1) patient-related factors, 2) product-related factors, and 3) administration-related factors. It provides a comprehensive overview of these immune response-mediated impacts, ranging from the development of anti-drug antibody (ADA) responses, injection site reactions (ISR), and injection site pain (ISP). Using immune response-mediated impacts as a focal point, the review discusses tools and strategies that can be used to evaluate the potential critical quality attributes (pCQAs) of therapeutic proteins as they have an impact on immunogenicity. These tools include various immunogenicity assessment assays spanning in silico, in vitro, ex vivo, in vivo animal models, and clinical tools. It also highlights a comprehensive repertoire of analytical characterization methods. Emphasis is placed on the importance of combined stage-appropriate use of these tools to minimize the risk of immunogenicity. Additionally, regulatory guidance, forums, and consortium landscapes are outlined to inform immunogenicity risk assessment strategy for therapeutic proteins. Ultimately, this integrated comprehensive immunogenicity testing strategy aims to advance the field of immunogenicity risk assessment to develop safe and efficacious protein therapeutics.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103870"},"PeriodicalIF":3.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266454","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}

引用次数: 0