Journal of pharmaceutical sciences最新文献

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IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2025-04-24 DOI: 10.1016/S0022-3549(25)00248-5
{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S0022-3549(25)00248-5","DOIUrl":"10.1016/S0022-3549(25)00248-5","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103790"},"PeriodicalIF":3.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863833","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
Metal-induced oxidation of polysorbate 80 in the presence of hydrogen peroxide: mechanistic studies 过氧化氢存在下金属诱导的聚山梨酸80氧化:机理研究
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2025-04-19 DOI: 10.1016/j.xphs.2025.103799
Yaqi Wu , Lin Zhang , Steve W. Dodd , Christian Schöneich
{"title":"Metal-induced oxidation of polysorbate 80 in the presence of hydrogen peroxide: mechanistic studies","authors":"Yaqi Wu ,&nbsp;Lin Zhang ,&nbsp;Steve W. Dodd ,&nbsp;Christian Schöneich","doi":"10.1016/j.xphs.2025.103799","DOIUrl":"10.1016/j.xphs.2025.103799","url":null,"abstract":"<div><div>Polysorbate 80 (PS80) is a commonly used surfactant in protein formulations and is highly susceptible to oxidative degradation. Here, we present mechanistic studies on metal-induced PS80 oxidation in the presence of hydrogen peroxide in acetate buffer. A total of 12 pharmaceutically relevant metal ions were tested, including Mn(II), Cu(II), Cu(I), Mg(II), Zn(II), Ca(II), Al(III), Pb(II), Sn(II), Co(II), Fe(III), Ni(II) and W(IV). The overall PS80 degradation was monitored by a fluorescence micelle assay (FMA) and the oxidation products were characterized by mass spectrometry (MS). Three metal ions, Cu(II), Co(II), and Fe(III), induced significant PS80 degradation and solutions containing these ions were subjected to further mechanistic studies. The extent of oxidation was dependent on both metal and peroxide concentrations. PS80 degradation catalyzed by Cu(II) and Co(II) was completely prevented by 250 µM and 500 µM ethylenediaminetetraacetic acid (EDTA), but only partially inhibited when catalyzed by Fe(III). The role for superoxide radical anion in the initiation of PS80 oxidation was examined by addition of Cu,Zn superoxide dismutase (SOD). The potential of the metal ions to generate free radicals was monitored with the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), followed by LC-MS analysis. Degradation mechanisms, particularly the initiation of the oxidation chain reactions, are discussed for each metal.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103799"},"PeriodicalIF":3.7,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899364","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
Intranasal delivery of temozolomide and desloratadine for brain tumour therapy: A cellular study on nasal epithelial toxicity, transport, and permeability 替莫唑胺和地氯雷他定鼻内给药用于脑肿瘤治疗:一项关于鼻上皮毒性、转运和通透性的细胞研究
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2025-04-14 DOI: 10.1016/j.xphs.2025.103795
Chun Yuen Jerry Wong , Elaine Leite , Hui Xin Ong , Daniela Traini
{"title":"Intranasal delivery of temozolomide and desloratadine for brain tumour therapy: A cellular study on nasal epithelial toxicity, transport, and permeability","authors":"Chun Yuen Jerry Wong ,&nbsp;Elaine Leite ,&nbsp;Hui Xin Ong ,&nbsp;Daniela Traini","doi":"10.1016/j.xphs.2025.103795","DOIUrl":"10.1016/j.xphs.2025.103795","url":null,"abstract":"<div><h3>Background</h3><div>The treatment of brain tumours, particularly glioblastoma (GBM), remains a significant challenge due to limited therapeutic options and the restrictive nature of the blood-brain barrier (BBB), which contributes to inadequate effective drug delivery. Temozolomide (TMZ), the first-line chemotherapeutic agent for GBM, offers only a modest survival benefit of 14.6 months and is associated with significant systemic side effects. Intranasal drug delivery has emerged as a promising non-invasive alternative, offering direct nose-to-brain (N2B) pathways to bypass the BBB. This method enables rapid and targeted drug transport while minimising systemic toxicity.</div></div><div><h3>Methods</h3><div>This study investigates the potential of desloratadine (DL), a repurposed non-sedating second-generation antihistamine, to enhance the therapeutic profile of TMZ in a nasal epithelial barrier model, representing the initial point of contact for N2B drug delivery. Cellular studies were conducted to evaluate the cytotoxicity, half-maximal inhibitory concentration, combination index, epithelial integrity, and drug transport properties of TMZ and DL alone and in combination. Transepithelial electrical resistance (TEER) and permeability coefficient (P<sub>app</sub>) assays assessed barrier integrity and drug transport across the nasal epithelial cells, while cytotoxicity studies confirmed selective targeting of nasal cells during intranasal administration without affecting bronchial cell viability.</div></div><div><h3>Results</h3><div>DL demonstrated significant intracellular retention in nasal epithelial cells, while TMZ exhibited efficient transport across the nasal barrier with moderate cellular retention. The combination of TMZ and DL reduced cytotoxicity in nasal epithelial cells compared to TMZ alone, suggesting DL’s protective role in mitigating TMZ-induced cytotoxic effects. TEER and P<sub>app</sub> analyses confirmed that both agents preserved nasal epithelial integrity, supporting their compatibility with N2B delivery. The synergistic effects of the combination therapy indicate an enhanced therapeutic profile for TMZ, with reduced off-target toxicity.</div></div><div><h3>Conclusion</h3><div>This study highlights the potential of a TMZ-DL drug combination therapy as a novel delivery strategy for brain tumour treatment. DL not only mitigates TMZ-induced cytotoxicity but also preserves the structural and functional integrity of the nasal epithelial barrier, addressing a critical translational gap in non-invasive drug delivery for brain tumours. Future work should focus on optimising dosing regimens and validating these findings in advanced 3D nasal models to facilitate clinical translation of this innovative therapeutic approach.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103795"},"PeriodicalIF":3.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894617","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
pH-sensitive sulfasalazine release from green-synthesized mesoporous Fe3O4@SiO2 nanocomposites using Opuntia ficus-indica extract 利用无花果树提取物合成的绿色介孔Fe3O4@SiO2纳米复合材料中ph敏感性磺胺嘧啶的释放
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2025-04-11 DOI: 10.1016/j.xphs.2025.103792
Muhammad Hossein Ashoub , Amin Golestani , Mahnaz Amiri , Razieh Razavi , Alireza Farsinejad
{"title":"pH-sensitive sulfasalazine release from green-synthesized mesoporous Fe3O4@SiO2 nanocomposites using Opuntia ficus-indica extract","authors":"Muhammad Hossein Ashoub ,&nbsp;Amin Golestani ,&nbsp;Mahnaz Amiri ,&nbsp;Razieh Razavi ,&nbsp;Alireza Farsinejad","doi":"10.1016/j.xphs.2025.103792","DOIUrl":"10.1016/j.xphs.2025.103792","url":null,"abstract":"<div><div>This study presents the green synthesis of mesoporous Fe<sub>3</sub>O<sub>4</sub>@SiO<sub>2</sub> nanocomposites using <em>Opuntia ficus-indica</em> extract for pH-sensitive delivery of sulfasalazine. The synthesized nanocomposites exhibited well-defined spherical morphology with particle sizes ranging from 80 to 120 nm and superior superparamagnetic properties with a saturation magnetization of 75.8 emu/g. X-ray diffraction analysis confirmed the formation of a pure magnetite phase with an average crystallite size of 17.37 nm, while nitrogen physisorption revealed a high specific surface area of 165.8 m²/g with uniform mesopores centered at 4.2 nm. The nanocomposites demonstrated exceptional drug loading characteristics with 81.1 % loading efficiency and 23.9 % loading capacity. pH-dependent release studies showed enhanced release under acidic conditions (82 % at pH 3.5) compared to physiological pH (50 % at pH 7.4), indicating potential for targeted drug delivery applications. Cytotoxicity studies using L929 cells and peripheral blood mononuclear cells (PBMCs) revealed remarkable biocompatibility at concentrations up to 200 µg/mL over 72 h. These findings establish the potential of green-synthesized mesoporous Fe<sub>3</sub>O<sub>4</sub>@SiO<sub>2</sub> nanocomposites as efficient carriers for pH-sensitive drug delivery systems, offering an environmentally friendly approach to developing advanced therapeutic platforms.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103792"},"PeriodicalIF":3.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894615","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 high-dose coenzyme Q10-emulgel for chronic oral therapy of deficient patients with secondary dysphagia 一种大剂量辅酶q10乳凝胶用于慢性口服治疗伴有继发性吞咽困难的缺陷患者
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2025-04-10 DOI: 10.1016/j.xphs.2025.103794
Ailin Camila Avila , Manuela R. Martinefski , Sergio Teves , Ana M. Rojas , Valeria P. Tripodi
{"title":"A high-dose coenzyme Q10-emulgel for chronic oral therapy of deficient patients with secondary dysphagia","authors":"Ailin Camila Avila ,&nbsp;Manuela R. Martinefski ,&nbsp;Sergio Teves ,&nbsp;Ana M. Rojas ,&nbsp;Valeria P. Tripodi","doi":"10.1016/j.xphs.2025.103794","DOIUrl":"10.1016/j.xphs.2025.103794","url":null,"abstract":"<div><div>Coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>) is the major endogenously fat-soluble antioxidant synthesized in the mitochondrion inner membrane as the electron carrier in the respiratory chain. In CoQ<sub>10</sub>-deficient patients, early high-oral doses (5–50 mg/kg/day) can constrain renal dysfunction and neurological signs. CoQ<sub>10</sub>, a typical class IV drug, with low bulk density, was dissolved at high-dose (1 g) in the oil phase (20:80 O/W) of a novel emulgel of small serving size (25 g) for its chronic administration in deficient patients with secondary dysphagia, as an alternative to maintain therapy adherence. The novelty is that CoQ<sub>10</sub> remained dissolved in 5 g of oil phase (MCT and coconut oils) per 25 g of alginate-emulgel. This was physically stable for 9 months at 25 °C as a “weak gel” type network, with high zeta potential (‒80 mV) being then the oil droplet size (5.0 μm) successfully maintained. The emulgel showed pseudoplastic behavior and four times lower viscosities than those of a contrast fluid used for swallow studies in dysphagic patients. Chemical stability of CoQ<sub>10</sub> was 100 % for 12 months. Emulgel administration (25 g/day) for 2 weeks increased CoQ<sub>10</sub> plasma concentration in 3.9 times. The number of doses for high CoQ<sub>10</sub> therapy can then be reduced, without swallowing discomfort.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103794"},"PeriodicalIF":3.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892143","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
Safety, pharmacokinetics and population pharmacokinetic model of TQH2722, a novel IL-4Rα monoclonal antibody in healthy subjects: a phase I, first-in-human, single-dose and multiple-dose escalation study 新型IL-4Rα单克隆抗体TQH2722在健康受试者中的安全性、药代动力学和群体药代动力学模型:一项I期、首次人体单剂量和多剂量递增研究
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2025-04-10 DOI: 10.1016/j.xphs.2025.103773
Xin Li , Xin Wang , Shixing Zhu , Feifei Sun , Yao Fu , Rongxin Ban , Hong Tan , Zhichao Yin , Zhenyue Gao , Zhongnan Xu , Ding Yu , Yu Cao
{"title":"Safety, pharmacokinetics and population pharmacokinetic model of TQH2722, a novel IL-4Rα monoclonal antibody in healthy subjects: a phase I, first-in-human, single-dose and multiple-dose escalation study","authors":"Xin Li ,&nbsp;Xin Wang ,&nbsp;Shixing Zhu ,&nbsp;Feifei Sun ,&nbsp;Yao Fu ,&nbsp;Rongxin Ban ,&nbsp;Hong Tan ,&nbsp;Zhichao Yin ,&nbsp;Zhenyue Gao ,&nbsp;Zhongnan Xu ,&nbsp;Ding Yu ,&nbsp;Yu Cao","doi":"10.1016/j.xphs.2025.103773","DOIUrl":"10.1016/j.xphs.2025.103773","url":null,"abstract":"<div><div>The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics (PK) of TQH2722, an Interleukin-4 receptor alpha (IL-4Rα) monoclonal antibody, in healthy subjects. In this randomized, double-blind and placebo-controlled trial, TQH2722 was subcutaneously injected as single-ascending dose (<em>n</em> = 46; 50, 150, 300, 600 and 1200 mg) or multiple-ascending dose (<em>n</em> = 20; 150 and 600 mg; four doses every 2 weeks). Subjects were monitored for adverse events and blood samples were collected for pharmacokinetics. A population pharmacokinetic model was developed and validated. TQH2722 was well tolerated with no serious or severe adverse events observed. After a single dose, the maximum concentration occurred at 3-7 days, with t<sub>1/2</sub> ranged from 2.65 to 17.43 days. Four repeated dosing caused about 3-fold degree of accumulation for C<sub>max</sub> and AUC. Regardless of single or multiple doses, the exposure showed a nonlinear and greater than dose proportional increase. A two-compartment model taking into account the mechanistic target-mediated drug disposition process with parallel linear and nonlinear Michaelis-Menten (MM) elimination and first-order absorption well described the pharmacokinetics of TQH2722. In conclusion, TQH2722 was safe and well tolerated, and its PK profiles were well characterized, supporting its further clinical development in patients.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103773"},"PeriodicalIF":3.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908069","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
Filling process-induced tribo-charging of lubricated and non-lubricated gelatine and HPMC capsules 润滑和非润滑明胶和HPMC胶囊的填充过程引起的摩擦充电。
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2025-04-05 DOI: 10.1016/j.xphs.2025.103781
M. Stankovic-Brandl , S. Zellnitz-Neugebauer , T. Wutscher , S. Biserni , A. Mercandelli , G. D’Elpidio , M. Kobler , F. Buttini , L. Andrade , S. Ecenarro , A. Paudel
{"title":"Filling process-induced tribo-charging of lubricated and non-lubricated gelatine and HPMC capsules","authors":"M. Stankovic-Brandl ,&nbsp;S. Zellnitz-Neugebauer ,&nbsp;T. Wutscher ,&nbsp;S. Biserni ,&nbsp;A. Mercandelli ,&nbsp;G. D’Elpidio ,&nbsp;M. Kobler ,&nbsp;F. Buttini ,&nbsp;L. Andrade ,&nbsp;S. Ecenarro ,&nbsp;A. Paudel","doi":"10.1016/j.xphs.2025.103781","DOIUrl":"10.1016/j.xphs.2025.103781","url":null,"abstract":"<div><div>Tribo-charging can negatively affect pharmaceutical processes and the quality of pharmaceutical products. This study investigates electrostatic charging during the filling of hard capsules intended to be used in dry powder inhalers (DPIs). Gelatin and HPMC capsules without and with external lubricants (sodium lauryl sulfate, carnauba wax, and magnesium stearate) were subjected to automatic powder filling at two filling speeds and two humidities. Tribo-charging was compared among capsules and correlated with filling parameters using a lactose and 1 % budesonide formulation. Further, we evaluated the aerodynamic performance post-filling to determine the relation of the process-induced tribo-charging on <em>in vitro</em> performance. Our findings indicate that capsules exhibited lower levels of charge before processing. Post-filling, gelatin capsules exhibited lower charge compared to HPMC capsules. External lubricants decreased the charge for both types of capsules. At higher filling humidity (51 % RH), capsules generally exhibited lower charge uptake comparing the 22 % RH condition; higher filling speed tends to reduce charge uptake. However, no clear correlation between the charging of capsules during filling and aerodynamic performance was observed. Processing seems to be more affected by the capsule surface properties (roughness and presence of surfactant), while the inhalation performance appears to be affected by the interplay of capsule material and process parameters (filling speed and humidity).</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103781"},"PeriodicalIF":3.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803597","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
Elucidation of the capping mechanism during the high-speed tableting process based on FEM simulation and fracture mechanics analysis 基于有限元模拟和断裂力学分析,阐述了高速压片过程中的旋盖机理。
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2025-04-04 DOI: 10.1016/j.xphs.2025.103784
Yusuke Imayoshi, Shuji Ohsaki, Hideya Nakamura, Satoru Watano
{"title":"Elucidation of the capping mechanism during the high-speed tableting process based on FEM simulation and fracture mechanics analysis","authors":"Yusuke Imayoshi,&nbsp;Shuji Ohsaki,&nbsp;Hideya Nakamura,&nbsp;Satoru Watano","doi":"10.1016/j.xphs.2025.103784","DOIUrl":"10.1016/j.xphs.2025.103784","url":null,"abstract":"<div><div>Capping is a phenomenon in which the cap of a tablet separates from the bonding area, thereby presenting a significant problem in tablet production. The compression speed is an important factor that affects the occurrence of capping. Capping is a phenomenon in which the tablet cap separates from the band of the tablet. However, the effect of compression speed on capping has not yet been fully elucidated. In this study, numerical analyses were performed using the finite element method (FEM) with the Drucker-Prager cap and Perzyna models at 40 mm/s to further understand the effect of compression speed on capping occurrence. The calculated loading curves agreed with the experimental curves at different tableting speeds. Moreover, the simulation results confirmed that the stress distribution inside the tablet became more non-uniform with increased compression speed. Additionally, we aimed to develop a prediction method for capping tendency using FEM simulation. Predicting the capping tendency by comparing the residual stress and tablet strength at the edge of the tablet is challenging. On the other hand, accurate predictions were achieved by comparing the stress intensity factor with the fracture toughness of the tablets, based on fracture mechanics principles. Our concept of predicting capping tendencies offers valuable insights for advancing research on the tableting process.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103784"},"PeriodicalIF":3.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795649","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
Oxaliplatin-loaded natural killer cell-derived exosomes for a safe and efficient chemoimmunotherapy of colorectal cancer 载奥沙利铂的自然杀伤细胞衍生外泌体用于安全有效的结直肠癌化学免疫治疗。
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2025-04-04 DOI: 10.1016/j.xphs.2025.103783
Yu Han , WeiCheng Zheng , YuYi Zhang , CaiLing Tong , PengBo Song , ZhongQuan Qi , ShiFeng Zhang
{"title":"Oxaliplatin-loaded natural killer cell-derived exosomes for a safe and efficient chemoimmunotherapy of colorectal cancer","authors":"Yu Han ,&nbsp;WeiCheng Zheng ,&nbsp;YuYi Zhang ,&nbsp;CaiLing Tong ,&nbsp;PengBo Song ,&nbsp;ZhongQuan Qi ,&nbsp;ShiFeng Zhang","doi":"10.1016/j.xphs.2025.103783","DOIUrl":"10.1016/j.xphs.2025.103783","url":null,"abstract":"<div><div>In recent years, the limited biocompatibility and serious side effects of oxaliplatin (L-OHP) have restricted its clinical application. Exosomes are biologically active vesicles with a double membrane structure secreted by almost all living cells. They transport biomolecules (e.g., cytokines, proteins, neurotransmitters, and lipids) used for inter-cellular regulation and communication to target cells. Because of their excellent bio-compatibility, highly permeable and low-toxicity properties, exosomes are receiving widespread attention and importance as a drug delivery platform. In this study, we demonstrated the successful isolation of saucer-like Natural Killer cell exosomes (NK-Exosomes, NK-Exos) from NK cell cultures by density gradient centrifugation. The nano-drug delivery system (L-OHP-Exos) was successfully prepared using sonication. This nanomedicine delivery system based on exosomes effectively delivers chemotherapy drugs into tumor cells, inhibiting their growth. Moreover, it enhances the generation of reactive oxygen species (ROS) within tumor cells through the synergistic action of its Fas ligand (FasL) and oxaliplatin, subsequently inducing apoptosis. Following a series of rigorous in vivo experimental validations, we further confirmed the dual benefits of NK-Exos: their inherent growth inhibitory effects on tumors and their ability to markedly potentiate the antineoplastic activity of <span>L</span>-OHP in colorectal cancer therapy. Due to the limited solubility of oxaliplatin in phospholipid bilayers, encapsulation of oxaliplatin within <span>L</span>-OHP-Exos minimizes its binding to plasma proteins post-intravenous administration, thereby augmenting the sustained release and bioavailability of the drug. This nano-drug delivery system offers a novel approach for the treatment of colorectal cancer and holds promising potential for clinical application.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103783"},"PeriodicalIF":3.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795727","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
Development of polylactic acid microneedles for enhanced transdermal delivery of desmopressin peptides: A computational study 开发用于增强去氨加压素肽透皮给药的聚乳酸微针:计算研究。
IF 3.7 3区 医学
Journal of pharmaceutical sciences Pub Date : 2025-04-03 DOI: 10.1016/j.xphs.2025.103777
Amirhossein Dashti , Milad Salimibani , Yegane Fanaei
{"title":"Development of polylactic acid microneedles for enhanced transdermal delivery of desmopressin peptides: A computational study","authors":"Amirhossein Dashti ,&nbsp;Milad Salimibani ,&nbsp;Yegane Fanaei","doi":"10.1016/j.xphs.2025.103777","DOIUrl":"10.1016/j.xphs.2025.103777","url":null,"abstract":"<div><div>Addressing the challenges associated with traditional injection therapies, this research marks a significant advancement in personalized and targeted therapeutic interventions, offering improved efficacy, convenience, and safety for patients undergoing peptide-based treatments. This article presents a research study on the development and assessment of polylactic acid (PLA) microneedles for enhancing the delivery of proteins and peptides, mainly focusing on the transdermal administration of desmopressin. Using simulations with COMSOL multiphysics software, it has been shown that PLA microneedles have excellent durability and controlled drug delivery capabilities, which promise efficient and patient-friendly transdermal drug delivery applications. Computational modeling results highlighted the dynamic behavior of desmopressin flow within the microneedle system, emphasizing accelerated drug transport capabilities. The utilization of dissolving microneedles in this study underscores the potential of microneedle technology as a promising solution for enhancing transdermal drug permeation, particularly for hydrophilic and macromolecular substances like proteins and peptides, thus opening new avenues for effective drug delivery systems.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103777"},"PeriodicalIF":3.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788637","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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