Asian Journal of Pharmaceutical Sciences最新文献

{"title":"A PET probe targeting polyamine transport system for precise tumor diagnosis and therapy","authors":"Ming Zhou ,&nbsp;Xiaoqin Yin ,&nbsp;Bei Chen ,&nbsp;Shuo Hu ,&nbsp;Wenhu Zhou","doi":"10.1016/j.ajps.2024.100924","DOIUrl":"10.1016/j.ajps.2024.100924","url":null,"abstract":"<div><p>Polyamine metabolism dysregulation is a hallmark of many cancers, offering a promising avenue for early tumor theranostics. This study presents the development of a nuclear probe derived from spermidine (SPM) for dual-purpose tumor PET imaging and internal radiation therapy. The probe, radiolabeled with either [⁶⁸Ga]Ga for diagnostic applications or [¹⁷⁷Lu]Lu for therapeutic use, was synthesized with exceptional purity, stability, and specific activity. Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells, showcasing outstanding tumor localization and target-to-non-target ratio. Mechanistic investigations employing polyamines, non-labeled precursor, and polyamine transport system (PTS) inhibitor, consistently affirmed the probeʼs targetability through recognition of the PTS. Notably, while previous reports indicated PTS upregulation in various tumor types for targeted therapy, this study observed no positive signals, highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis. Furthermore, when labeled with [¹⁷⁷Lu], the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival. Investigations into biodistribution, excretion, and biosafety in healthy humans laid a robust foundation for clinical translation. This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics, offering promising prospects for clinical implementation.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 3","pages":"Article 100924"},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000412/pdfft?md5=157f1e7aca3e72950e4a7d25d1af5d05&pid=1-s2.0-S1818087624000412-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140756333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies","authors":"Zhining Ma ,&nbsp;Yuequan Wang ,&nbsp;Huiyang He ,&nbsp;Tong Liu ,&nbsp;Qikun Jiang ,&nbsp;Xiaohong Hou","doi":"10.1016/j.ajps.2024.100928","DOIUrl":"10.1016/j.ajps.2024.100928","url":null,"abstract":"<div><p>Flurbiprofen (FB), a nonsteroidal anti-inflammatory drug, is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects. However, the racemic nature of its commercially available formulation (Ocufen®) limits the full potential of its therapeutic activity, as the (<em>S</em>)-enantiomer is responsible for the desired anti-inflammatory effects. Additionally, the limited corneal permeability of FB significantly restricts its bioavailability. In this study, we successfully separated the chiral isomers of FB to obtain the highly active (<em>S</em>)-FB. Subsequently, utilizing ion-pairing technology, we coupled (<em>S</em>)-FB with various counter-ions, such as sodium, diethylamine, trimethamine (TMA), and l-arginine, to enhance its ocular bioavailability. A comprehensive evaluation encompassed balanced solubility, octanol-water partition coefficient, corneal permeability, ocular pharmacokinetics, tissue distribution, and <em>in vivo</em> ocular anti-inflammatory activity of each chiral isomer salt. Among the various formulations, S-FBTMA exhibited superior water solubility (about 1–12 mg/ml), lipid solubility (1&lt; lg P_ow &lt; 3) and corneal permeability. In comparison to Ocufen®, S-FBTMA demonstrated significantly higher <em>in vivo</em> anti-inflammatory activity and lower ocular irritability (such as conjunctival congestion and tingling). The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 3","pages":"Article 100928"},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S181808762400045X/pdfft?md5=d713cf3b9937b0a72348e2d4c6af4318&pid=1-s2.0-S181808762400045X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141139770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances on thermosensitive hydrogels-mediated precision therapy","authors":"Hao Chen ,&nbsp;Jiangmei Xu ,&nbsp;Jiangwei Sun ,&nbsp;Yongxin Jiang ,&nbsp;Wang Zheng ,&nbsp;Wei Hu ,&nbsp;Haisheng Qian","doi":"10.1016/j.ajps.2024.100911","DOIUrl":"10.1016/j.ajps.2024.100911","url":null,"abstract":"<div><p>Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites, increased therapeutic efficacy, and reduced adverse effects. Over the past few years, sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential. These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature. Inspired by their unique properties, thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine. In this review, the state-of-the-art developments in thermosensitive hydrogels for precision therapy are investigated, which covers from the thermo-gelling mechanisms and main components to biomedical applications, including wound healing, anti-tumor activity, osteogenesis, and periodontal, sinonasal and ophthalmic diseases. The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 3","pages":"Article 100911"},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S181808762400028X/pdfft?md5=9e1a9f4505e3f11dd3f195e4a27aff17&pid=1-s2.0-S181808762400028X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140778325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoids-based prodrug design: Current strategies and research progress","authors":"Hongbing Liu ,&nbsp;Muse Ji ,&nbsp;Peifu Xiao ,&nbsp;Jingxin Gou ,&nbsp;Tian Yin ,&nbsp;Haibing He ,&nbsp;Xing Tang ,&nbsp;Yu Zhang","doi":"10.1016/j.ajps.2024.100922","DOIUrl":"10.1016/j.ajps.2024.100922","url":null,"abstract":"<div><p>Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract. These notorious side effects seriously compromise patients' quality of life, especially in patients with chronic diseases. Therefore, glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention. Among them, prodrugs have the advantages of low investment, low risk, and high success rate, making them a promising strategy. In this review, we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades, including polymer-based prodrugs, dendrimer-based prodrugs, antibody-drug conjugates, peptide-drug conjugates, carbohydrate-based prodrugs, aliphatic acid-based prodrugs and so on. Besides, we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs. This review is expected to be helpful for the research and development of novel GCs and prodrugs.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 3","pages":"Article 100922"},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000394/pdfft?md5=1a86498bf675c0b810b1b5ce25a9df62&pid=1-s2.0-S1818087624000394-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140781057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis","authors":"Rui Wang ,&nbsp;Tongyao Liu ,&nbsp;Xinhong Li ,&nbsp;Enhao Lu ,&nbsp;Yiting Chen ,&nbsp;Kuankuan Luo ,&nbsp;Tao Wang ,&nbsp;Xueli Huang ,&nbsp;Zhiwen Zhang ,&nbsp;Shilin Du ,&nbsp;Xianyi Sha","doi":"10.1016/j.ajps.2024.100913","DOIUrl":"10.1016/j.ajps.2024.100913","url":null,"abstract":"<div><p>Flare and multiple recurrences pose significant challenges in gouty arthritis. Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences. It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis, calling for therapeutic systems to achieve these two goals simultaneously. In this study, we propose a biomimetic integrated nanozyme, HMPB-Pt@MM, comprising platinum nanozyme and hollow Prussian blue. It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages. Additionally, it rapidly targets inflamed ankles through the camouflage of macrophage membranes. Furthermore, HMPB-Pt@MM exhibits urate oxidase-like capabilities, continuously metabolizing locally elevated uric acid concentrations, ultimately inhibiting multiple recurrences of gouty arthritis. In summary, HMPB-Pt@MM integrates ROS clearance with uric acid metabolism, offering a promising platform for the treatment of gouty arthritis.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 3","pages":"Article 100913"},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000308/pdfft?md5=ae817b13af18eab2a96c3b71ceede50d&pid=1-s2.0-S1818087624000308-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140788973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing HepG2 cell apoptosis with a combined nanoparticle delivery of miR-128–3p agomir and Oroxin B: A novel drug delivery approach based on PI3K-AKT and VEGF pathway crosstalk","authors":"Hechen Wang,&nbsp;Xudan Shen,&nbsp;Jiatong Liu,&nbsp;Xinlan Zhu,&nbsp;Su Zeng,&nbsp;Sheng Cai","doi":"10.1016/j.ajps.2024.100909","DOIUrl":"10.1016/j.ajps.2024.100909","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) shows the highest morbidity among liver cancers and is a major contributor to cancer-associated mortality. It is characterized by genetic mutations in hepatocytes, leading to uncontrolled cell growth and proliferation. Current treatment include surgery, chemotherapy and immunotherapy; however, chemotherapeutics, which focus on single-targeted drug therapy, are still associated with certain limitations and may affect the treatment outcomes. Compared with chemotherapy drugs, natural products also show the anticancer effect of HCC and hypotoxicity, but overall low activity of natural products limits their further application. MmiRNAs can modulate post-transcriptional functions of target genes. An increasing body of evidence has demonstrated that miRNAs are the key regulators in HCC by targeting different molecules in different signaling pathways. However, miRNAs are fragile and liable to catabolism by RNases in serum and other body fluids and small molecules separated from natural products may have limited bio-availability. According to this background, a chitosan based, targeted sustained-release nanoparticle delivery miR-128–3p agomir (NA-miR-128–3p) was developed in this work. This nanoparticle was prepared by pentasodium tripolyphosphate (TPP), chitosan hydrochloride, and miR-128–3p agomir with target aptamer which was loaded into the chitosan nanoparticle by self-assembly. It can intervene in HCC progress by affecting AKT1 expression. Based on this, a novel, efficient, long-acting, multi-mechanism, low-dosage combination drug delivery strategy was proposed in this work and showed a prominent anti-tumor effect. NA-miR-128–3p combined with natural product Oroxin B significantly affected HCC progression by the interference with VEGF and PI3K-AKT pathways, better than using NA-miR-128–3p and Oroxin B alone. Taken together, this nanoparticle and combinative administration compensate for the shortcomings of the fragile RNA drugs and the low activity of natural products, with high prospects in HCC treatment.</div></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"20 3","pages":"Article 100909"},"PeriodicalIF":10.7,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor microenvironment reprogramming by nanomedicine to enhance the effect of tumor immunotherapy","authors":"Yu Huang ,&nbsp;Hui Fan ,&nbsp;Huihui Ti","doi":"10.1016/j.ajps.2024.100902","DOIUrl":"10.1016/j.ajps.2024.100902","url":null,"abstract":"<div><p>With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100902"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000199/pdfft?md5=999152305d8eff90cdeed688376a5a6d&pid=1-s2.0-S1818087624000199-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140156861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines","authors":"Cong Li,&nbsp;Lihong Wang,&nbsp;Kexin Zhang,&nbsp;Zeyu Wang,&nbsp;Zhihang Li,&nbsp;Zehao Li,&nbsp;Lijiang Chen","doi":"10.1016/j.ajps.2024.100906","DOIUrl":"10.1016/j.ajps.2024.100906","url":null,"abstract":"<div><p>Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils <em>in vivo</em>, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. <em>In vivo</em> and <em>vitro</em> experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100906"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000230/pdfft?md5=933a0e2aec5ccb44aba58479cf19b745&pid=1-s2.0-S1818087624000230-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140204316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet-derived microparticles and their cargos: The past, present and future","authors":"Jingwen Guo ,&nbsp;Bufeng Cui ,&nbsp;Jie Zheng ,&nbsp;Chang Yu ,&nbsp;Xuran Zheng ,&nbsp;Lixin Yi ,&nbsp;Simeng Zhang ,&nbsp;Keke Wang","doi":"10.1016/j.ajps.2024.100907","DOIUrl":"10.1016/j.ajps.2024.100907","url":null,"abstract":"<div><p>All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100907"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000242/pdfft?md5=3ff47aa50b4d9125dc4ec813343a5209&pid=1-s2.0-S1818087624000242-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140282817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury","authors":"Yunhan Zhang ,&nbsp;Zhulin Zou ,&nbsp;Shuang Liu ,&nbsp;Fangfang Chen ,&nbsp;Minglu Li ,&nbsp;Haoyang Zou ,&nbsp;Haiyan Liu ,&nbsp;Jianxun Ding","doi":"10.1016/j.ajps.2024.100886","DOIUrl":"10.1016/j.ajps.2024.100886","url":null,"abstract":"<div><p>Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 2","pages":"Article 100886"},"PeriodicalIF":10.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000035/pdfft?md5=4a2ddbf84e1e1e953be25b615bca6486&pid=1-s2.0-S1818087624000035-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139772324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}