Journal of pharmaceutical sciences最新文献

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Limitation of Anion Exchange Chromatography and Potential Application of Hydrophobic Interaction Chromatography for Monitoring AAV9 Capsid Degradation Upon Thermal Stress. 阴离子交换色谱法的局限性和疏水相互作用色谱法在监测热应力下 AAV9 荚膜降解过程中的潜在应用
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2024-11-15 DOI: 10.1016/j.xphs.2024.11.005
Antonela Rodriguez, Ali Banazadeh, Amr Ali, Rajeeva Singh, Chen Zhou
{"title":"Limitation of Anion Exchange Chromatography and Potential Application of Hydrophobic Interaction Chromatography for Monitoring AAV9 Capsid Degradation Upon Thermal Stress.","authors":"Antonela Rodriguez, Ali Banazadeh, Amr Ali, Rajeeva Singh, Chen Zhou","doi":"10.1016/j.xphs.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.11.005","url":null,"abstract":"<p><p>Adeno-Associated Virus (AAV) is often selected as the vector of choice for gene therapy due to its superior clinical performance compared to other gene delivery systems. Currently the characterization of AAV degradation, especially the chemical degradation of capsid, has been limited due to lack of suitable methods. Our study using AAV9 as a model molecule shows that anion exchange chromatography (AEX) as a charge-based separation method has limitations in monitoring the chemical degradation of AAV9 capsid due to a confounding effect from DNA cargo ejection. We developed a hydrophobic interaction chromatography (HIC) method, free from DNA interference, that could serve as a quick and reliable alternative to resource-demanding peptide mapping method for monitoring AAV capsid chemical degradation. Compared with brief thermal stress at 75 °C, AAV9 capsid exhibited much higher levels of chemical degradation but slower capsid titer loss upon extended exposure for 4 weeks at 40 °C.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648001","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
Controlled Self-Assembly of Macrocyclic Peptide into Multifunctional Photoluminescent Nanoparticles. 将大环肽受控自组装成多功能光致发光纳米粒子。
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2024-11-15 DOI: 10.1016/j.xphs.2024.11.006
Ranga Dissanayake, Nauman Nazeer, Zeyaealdin Zarei, Adnan Murad Bhayo, Marya Ahmed
{"title":"Controlled Self-Assembly of Macrocyclic Peptide into Multifunctional Photoluminescent Nanoparticles.","authors":"Ranga Dissanayake, Nauman Nazeer, Zeyaealdin Zarei, Adnan Murad Bhayo, Marya Ahmed","doi":"10.1016/j.xphs.2024.11.006","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.11.006","url":null,"abstract":"<p><p>Self-assembled peptide nanoparticles are unique stimuli responsive biodegradable materials with applications in biomedicines as delivery carriers and imaging agents. This study investigates the controlled self-assembly of chicken Angiogenin 4 derived immunomodulatory macrocyclic peptide (mCA4-5) in the presence of an inert amphipathic stabilizing peptide and as a function of pH, temperature and presence of ions to yield optically active, physiologically stable and biodegradable peptide nanoparticles. The photoluminescent peptide nanoparticles (PLPNs) produced were characterized for the size, surface charge, optical properties and crystallinity. The carvacrol loaded nanoparticles prepared by facile encapsulation of the drug during the self-assembly process were evaluated for the drug release efficacies, as a function of pH and in the presence of reducing agent. Carvacrol loaded, physiologically stable PLPNs obtained with high conversion efficacy were highly effective against planktonic bacteria and bacterial biofilms and efficiently eradicated intracellular bacteria in infected macrophages and fibroblast. Furthermore, the drug-loaded nanoparticles exhibited significant antioxidant activities and immunomodulatory effects, highlighting their multifunctional therapeutic potential.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647985","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
Ultrasound/Magnetic Resonance Bimodal Imaging-Guided CD20-Targeted Multifunctional Nanoplatform for Photothermal/Chemo Synergistic Therapy of B-Cell Lymphoma. 超声/磁共振双模成像引导的 CD20 靶向多功能纳米平台用于 B 细胞淋巴瘤的光热/化疗协同治疗
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2024-11-15 DOI: 10.1016/j.xphs.2024.11.004
Zhengji Wang, Jian Huang, Weiyang Lv, Chunxin Huang, Ying Wang, Xing Li, Huilin Liu, Liguo Hao
{"title":"Ultrasound/Magnetic Resonance Bimodal Imaging-Guided CD20-Targeted Multifunctional Nanoplatform for Photothermal/Chemo Synergistic Therapy of B-Cell Lymphoma.","authors":"Zhengji Wang, Jian Huang, Weiyang Lv, Chunxin Huang, Ying Wang, Xing Li, Huilin Liu, Liguo Hao","doi":"10.1016/j.xphs.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.11.004","url":null,"abstract":"<p><p>B-cell lymphoma has a poor prognosis due to difficulties in early diagnosis and the negative effects of systemic chemotherapy. Therefore, there is an urgent need to develop highly accurate and effective theranostic strategies for B-cell lymphoma. In this study, we designed a poly (lactic-co-glycolic acid) (PLGA)-based theranostic nanoplatform (denoted as TscNPs) to achieve ultrasound (US)/magnetic resonance (MR) bimodal imaging-guided photothermal (PTT)/chemo synergistic therapy of B-cell lymphoma. The nanoplatform was conjugated with a CD20 monoclonal antibody specifically targeting B-cell lymphoma to promote tumor accumulation. Encapsulated superparamagnetic iron oxide nanoparticles (SPIONs) as photothermal and MR imaging agents enabled thermal ablation of tumors and imaging-guided tumor therapy. When exposed to near-infrared (NIR) laser, TscNPs generate heat that induces optical droplet vaporization (ODV) of perfluoropentane (PFP), which transforms into microbubbles. This process not only enhanced ultrasound imaging, but also facilitated the release of celastrol (CST) from the nanoplatform, ultimately achieving a PTT/chemo synergistic therapy effect. In the tumor-bearing nude mice model, TscNPs were effectively accumulated in the tumor region. Furthermore, the combined treatment mode of TscNPs and NIR laser irradiation demonstrated a tumor inhibition rate of approximately 96.57%, which was significantly superior to the rates observed with PTT or chemotherapy alone. These results suggest that the multifunctional theranostic nanoplatform represents a promising new strategy for the therapy of B-cell lymphoma.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648003","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
A Workflow for Accurate and Consistent Quantitation of Host Cell Proteins by SWATH LC-MS/MS Analysis to Support Process Development. 通过 SWATH LC-MS/MS 分析对宿主细胞蛋白质进行准确一致定量的工作流程,以支持工艺开发。
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2024-11-15 DOI: 10.1016/j.xphs.2024.11.007
Jia Guo, Regina Kufer, Midori Greenwood-Goodwin, Stefanie Wohlrab, Fem Woodruff, Delia Li, Katharina Reckermann, Jonghae Youn, Dilip Kumar Reddy Kandula, Lei Xiong, Feng Yang
{"title":"A Workflow for Accurate and Consistent Quantitation of Host Cell Proteins by SWATH LC-MS/MS Analysis to Support Process Development.","authors":"Jia Guo, Regina Kufer, Midori Greenwood-Goodwin, Stefanie Wohlrab, Fem Woodruff, Delia Li, Katharina Reckermann, Jonghae Youn, Dilip Kumar Reddy Kandula, Lei Xiong, Feng Yang","doi":"10.1016/j.xphs.2024.11.007","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.11.007","url":null,"abstract":"<p><p>Residual host cell proteins (HCPs) in drug products may impact product quality, stability, efficacy and safety. To support consistent and accurate quantitative analysis for low levels of HCPs (≥ 1 ppm), the data-independent sequential window acquisition of all theoretical fragment ion spectra (SWATH) MS/MS-based method provides unique advantages over data dependent acquisition (DDA) or targeted methods for HCP identification and quantification. However, SWATH MS/MS-based methods can generate biased quantitative results that are highly dependent on the selected reference protein. In this study, we enhanced the accuracy of SWATH-based HCP quantitation relative to a spiked-in reference protein by selecting appropriate reference proteins based on their ranking values. We developed a reliable SWATH-based method for quantifying specific HCPs by adding sodium deoxycholate (SDC) during digestion to enhance both protein detection and quantitation consistency. By combining SWATH-based quantitation with standard addition, we showed its use in measuring HCP levels with good accuracy and reproducibility, confirmed by both targeted MRM-MS/MS and ELISA. Additionally, we demonstrated an automated Spectronaut data analysis workflow can efficiently generate SWATH quantitative results for HCPs in different in-process pools. Using SWATH-based quantitation, we were able to measure specific HCPs (e.g. Peroxiredoxin-1) and support process development with good throughput and quantitation consistency.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647975","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
Synchrotron computed tomography combined with AI-based image analysis for the advanced characterization of spray dried amorphous solid dispersion particles. 同步辐射计算机断层扫描与基于人工智能的图像分析相结合,用于喷雾干燥无定形固体分散颗粒的高级表征。
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2024-11-14 DOI: 10.1016/j.xphs.2024.10.033
Tatiana Marcozzi, Sruthika Baviriseaty, Phillip Yawman, Shawn Zhang, Chris Vervaet, Valérie Vanhoorne, Sune Andersen
{"title":"Synchrotron computed tomography combined with AI-based image analysis for the advanced characterization of spray dried amorphous solid dispersion particles.","authors":"Tatiana Marcozzi, Sruthika Baviriseaty, Phillip Yawman, Shawn Zhang, Chris Vervaet, Valérie Vanhoorne, Sune Andersen","doi":"10.1016/j.xphs.2024.10.033","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.033","url":null,"abstract":"<p><p>Particle engineering aims to design particles with specific properties. A deeper understanding of how particle formation relates to material attributes and process conditions are critical to strengthen knowledge on powder properties and enhance modeling capabilities. New, alternative powder characterization techniques can offer novel and more accurate measures for particle properties, giving more advanced characterization information. In this context, a case study is presented in which spray dried amorphous solid dispersion powders produced by modifying process conditions were characterized by both well-established compendial methods (i.e., laser light diffraction, SEM image analysis, bulk and tapped density, and gas adsorption), as well as a new method combining synchrotron computed tomography (SyncCT) with AI-based image analysis. SyncCT was used to classify and quantify the spray dried particles as hollow spheres and solid particles, giving a more detailed quality measure of the particle shape, as they impact downstream processing differently. Moreover, hollow particle wall thicknesses, as well as internal and external particle surface areas were measured by SyncCT. Altogether, powder characterization data from SyncCT show similar trends to that obtained from compendial techniques and giving additional quality measure regarding particle shape, showing promise of this new and advanced characterization method.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643772","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
Highly Sensitive and Robust LC-MS/MS Method for Determination up to 15 Small Molecule Nitrosamine Impurities in Pharmaceutical Drug Substances. 高灵敏度和稳健的 LC-MS/MS 方法,用于测定药物中多达 15 种小分子亚硝胺杂质。
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2024-11-14 DOI: 10.1016/j.xphs.2024.11.003
Swapna Daripelli, Nitin Ashok Jadhav, Anindita Sarkar, Vinit Yadav, Mayank Bhanti, Mrunal Jaywant
{"title":"Highly Sensitive and Robust LC-MS/MS Method for Determination up to 15 Small Molecule Nitrosamine Impurities in Pharmaceutical Drug Substances.","authors":"Swapna Daripelli, Nitin Ashok Jadhav, Anindita Sarkar, Vinit Yadav, Mayank Bhanti, Mrunal Jaywant","doi":"10.1016/j.xphs.2024.11.003","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.11.003","url":null,"abstract":"<p><p>Nitrosamine impurities have been classified as probable human carcinogens for decades. These impurities were reported in water, food, tobacco, pesticides, and plastics but received attention in mid-2018 when N-nitrosodimethylamine (NDMA) was reported in valsartan drug products. Subsequently, it was revealed that several small molecule and complex nitrosamine impurities can form in any active pharmaceutical ingredient (API) or drug product in which secondary or tertiary amines are present (as API or as impurities) along with a nitrosating agent. Consequently, regulators have provided several guidelines for the risk assessment of nitrosamine formation during manufacturing, storage, or from contaminated supply chains. This has led to a demand for validated analytical methods that quantify N-nitrosamine impurities in pharmaceutical products. In this study, a highly sensitive and robust analytical method was developed and validated for quantitatively determining up to 15 small nitrosamines at low levels (0.01 ppm) in sartan drug substances. The study also suggests that this method can be extended not only to corresponding sartan drug products but could also be used as a generic screening method to test a variety of drug substances, and drug products with the minimum required optimization of method conditions.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643771","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
Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Voriconazole. 速释口服固体制剂的生物豁免专论:伏立康唑。
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2024-11-13 DOI: 10.1016/j.xphs.2024.10.055
Kristian Beran, Bertil Abrahamsson, Naseem Charoo, Rodrigo Cristofoletti, René Holm, Atsushi Kambayashi, Peter Langguth, Alan Parr, James E Polli, Vinod P Shah, Jennifer Dressman
{"title":"Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Voriconazole.","authors":"Kristian Beran, Bertil Abrahamsson, Naseem Charoo, Rodrigo Cristofoletti, René Holm, Atsushi Kambayashi, Peter Langguth, Alan Parr, James E Polli, Vinod P Shah, Jennifer Dressman","doi":"10.1016/j.xphs.2024.10.055","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.055","url":null,"abstract":"<p><p>According to the ICH M9 Guideline, the triazole antifungal voriconazole is a Biopharmaceutics Classification System (BCS) class II drug, being highly soluble at the highest dose strength but not at the highest single dose. Although the ICH M9 allows for consideration of BCS-based biowaivers in such cases, voriconazole does not meet the additional requirement of dose proportional pharmacokinetics (PK) over the therapeutic dose range. By contrast, if the classification were based on the FDA solubility criteria that were in place prior to ICH M9 (based on the highest dose strength), voriconazole would belong to BCS class I and thus qualify for the BCS-based biowaiver. Since the highest oral dose strength of voriconazole dissolves very rapidly under all BCS conditions, and comparative in vitro dissolution of different tablet formulations aligns with the demonstration of BE in clinical studies, it seems that the ICH Guideline may be unnecessarily restrictive in the case of voriconazole. Therefore, this review discusses potential revisions of eligibility criteria and the extension of biowaiver approvals to encompass a wider range of appropriate drugs. Specifically, a classification system that is more relevant to in vivo conditions, the refined Developability Classification System (rDCS), coupled with biorelevant dissolution testing, may be more applicable to compounds like voriconazole.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639173","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
Impact of Citrate on Mitigating Iron Mediated Polysorbate 80 Degradation in Biotherapeutic Formulation Placebos. 柠檬酸盐对缓解生物治疗配方安慰剂中铁介导的聚山梨醇酯 80 降解的影响
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2024-11-13 DOI: 10.1016/j.xphs.2024.10.038
Rong-Sheng Yang, Chengbei Li, Liliana Henriquez, Hongxia Wang, Jainik Panchal, Wendy Zhong, Hillary Schuessler
{"title":"Impact of Citrate on Mitigating Iron Mediated Polysorbate 80 Degradation in Biotherapeutic Formulation Placebos.","authors":"Rong-Sheng Yang, Chengbei Li, Liliana Henriquez, Hongxia Wang, Jainik Panchal, Wendy Zhong, Hillary Schuessler","doi":"10.1016/j.xphs.2024.10.038","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.038","url":null,"abstract":"<p><p>Polysorbate 80 (PS80), a widely used polymeric surfactant in biotherapeutic formulation, possesses a unique structural composition that effectively prevents protein aggregation in highly concentrated protein drug formulations. However, PS80 is susceptible to hydrolysis, due to the presence of fatty acid esters that can be enzymatically hydrolyzed, The unsaturated bonds in the fatty acids are prone to oxidative degradation when exposed to air, especially in the presence of transition metals such as iron and copper, which may be introduced during production and purification processes or from contamination in raw materials used in drug formulation. The degradation of PS80, particularly through metal-mediated oxidative degradation, poses a significant challenge for the industry. Among the identified trace metals, iron plays a crucial role as the redox reaction between ferrous ion (Fe(II)) and ferric ion (Fe(III)) generates radicals that initiate the degradation process. In order to investigate the impact of iron on PS80 degradation and understand the mechanism of iron-catalyzed oxidation, we utilized charge-reduction mass spectrometry and two-dimensional ion density mapping technologies to characterize the degradation of PS80. This method has proven to be a convenient and effective tool for the quick and detailed profiling of PS80, allowing for visual monitoring and examination of the changes that reflect the difficult-to-identify and easy-to-miss oxidized species of PS80. Additionally, a high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry method was developed for the separation and measurement of Fe(II) and Fe(III). Through this investigation, we determined that the involvement of Fe(II)/Fe(III) in PS80 degradation is a temperature dependent process. Furthermore, we found citrate not only promotes the conversion of Fe(II) to Fe(III), but it also chelates Fe(III) and prevents its reduction to Fe(II), thus inhibiting the initiation of the PS80 degradation. Therefore, the addition of citrate can be a crucial ingredient for controlling the degradation of PS80 in biologic drug substances and products. Overall, this investigation has provided valuable insights to enhance product stability, optimize processes, and ensure the quality of formulations containing PS80.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639192","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
Mechanistic characterization of iron-catalyzed oxidation of polysorbate 80: The role of ferrous iron, hydrogen peroxide, and superoxide. 铁催化聚山梨醇酯 80 氧化的机理特征:亚铁、过氧化氢和超氧化物的作用。
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2024-11-12 DOI: 10.1016/j.xphs.2024.10.053
David S Richards, Yaqi Wu, Christian Schöneich
{"title":"Mechanistic characterization of iron-catalyzed oxidation of polysorbate 80: The role of ferrous iron, hydrogen peroxide, and superoxide.","authors":"David S Richards, Yaqi Wu, Christian Schöneich","doi":"10.1016/j.xphs.2024.10.053","DOIUrl":"10.1016/j.xphs.2024.10.053","url":null,"abstract":"<p><p>We investigated the role of individual radical species during Fe-catalyzed oxidation of PS80. Solutions containing 1 gL<sup>-1</sup> PS80 (0.1 % w/v) in 10 mM acetate buffer (pH 6) were exposed to various amounts of either Fe(II) or Fe(III), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), and various enzymes or antioxidants. PS80 oxidation was measured using a fluorescence micelle assay (FMA) alongside LC-MS. Hydrogen peroxide inhibited PS80 oxidation in the presence of Fe(II) but promoted oxidation in the presence of Fe(III). Furthermore, Ferrostatin-1 (Fer-1), an antioxidant which is known to preferentially react with alkoxy radicals, inhibited PS80 oxidation in the presence of Fe(II). Superoxide dismutase (SOD) partially inhibited PS80 oxidation in the presence of either Fe(II) or Fe(III), suggesting that superoxide plays a role in both cases. Ferryl species (Fe<sup>IV</sup>=O) or hydroxyl radicals (HO•), produced by the Fenton reaction, do not play a major role in the oxidation of PS80. Rather, oxidation was initiated by the reaction of both Fe(II) and Fe(III) with pre-existing lipid hydroperoxides on PS80, as well as via superoxide.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622887","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
In vitro Analysis of XLAsp-P2 Peptide Loaded Cellulose Acetate Nanofiber for Wound Healing. 用于伤口愈合的 XLAsp-P2 肽负载醋酸纤维素纳米纤维的体外分析
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2024-11-12 DOI: 10.1016/j.xphs.2024.10.050
Saranya Selvaraj, Monali Perera, Piumika Yapa, Imalka Munaweera, Inoka C Perera, Tharindu Senapathi, Laksiri Weerasinghe
{"title":"In vitro Analysis of XLAsp-P2 Peptide Loaded Cellulose Acetate Nanofiber for Wound Healing.","authors":"Saranya Selvaraj, Monali Perera, Piumika Yapa, Imalka Munaweera, Inoka C Perera, Tharindu Senapathi, Laksiri Weerasinghe","doi":"10.1016/j.xphs.2024.10.050","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.050","url":null,"abstract":"<p><p>Recently, nanofiber-based wound dressings are currently a viable strategy to expedite the healing of wounds by providing a suitable microenvironment for tissue growth with active ingredients. This research study subjects the development of electrospun cellulose acetate (CA) nanofibers loaded with the XLAsp-P2, an antimicrobial peptide (AMP) that holds great potential for enhanced wound healing as a therapeutic agent. The synthesized XLAsp-P2-loaded CA nanofibers were fabricated via three loading percentages, 0.1 %, 0.2 %, and 0.3 % w/w, and characterized and evaluated their antimicrobial potential with MTT assay and Agar overlay methods as an alternative strategy. FT-IR analysis confirmed the compatibility of the peptide loaded CA nanocomposite, showing distinct peaks corresponding to the constituent materials. Scanning electron microscopy (SEM) analysis was employed to characterize the morphology of electrospun peptide CA nanocomposites and illustrate the fiber's size at the nanoscale. The in vitro release study during the 24 hrs, 87 % of the peptide was released which was approximately 5.2 mg; which was closer matched to the square root model of Higuchi at room temperature. MTT assay presented sensitive results towards Gram-positive bacteria compared to Gram Negative bacteria; which corresponded to the inhibition zones of the Agar overlay method proving that Escherichia coli (ATCC 25922) 17.66 ± 0.38 mm and Pseudomonas aeruginosa (ATCC 27853) 17.44 ± 0.38 mm exhibited moderate susceptibility, while Staphylococcus aureus (ATCC 25923)19.89 ± 0.69 mm and Bacillus cereus (ATCC 11778) 23.00 ± 0.33 mm showed promising responses. Collectively, The study's findings indicate that the XLAsp-P2 incorporated CA mat possesses an opportunity to function as an efficient platform for delivering therapeutic peptides.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622886","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
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