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Current Opinion in Pharmacology最新文献

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Precision medicine and immunotherapeutic approaches for relapsed/refractory paediatric acute myeloid leukaemia 复发/难治性小儿急性髓性白血病的精准医学和免疫治疗方法
IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-06-19 DOI: 10.1016/j.coph.2025.102546
Caroline C. Smith , Sarah K. Tasian
Despite improved clinical outcomes amongst children and adolescents/young adults with acute myeloid leukaemia (AML) treated with modern risk-adapted frontline therapies, approximately one third of patients will relapse. Significant advances in comprehensive cytomolecular genetic diagnostics and correlation with survival outcomes via clinical trial data have identified paediatric patients with AML at highest risk of primary chemoresistance and/or subsequent relapse for whom new treatment approaches are needed. This brief North American-based perspective highlights promising small molecule inhibitors and antibody-based and cellular immunotherapies with demonstrated or emerging activity in specific high-risk subtypes of paediatric AML and outlines potential treatment strategies for children and adolescents/young adults with relapsed AML.
尽管采用现代风险适应一线疗法治疗急性髓性白血病(AML)的儿童和青少年/年轻人的临床结果有所改善,但仍有大约三分之一的患者会复发。通过临床试验数据,全面的细胞分子遗传学诊断和与生存结果的相关性取得了重大进展,确定了原发性化疗耐药和/或随后复发风险最高的儿科AML患者,需要新的治疗方法。这篇以北美为基础的简短文章强调了小分子抑制剂、基于抗体和细胞免疫疗法的前景,这些疗法在特定的高危儿科AML亚型中已证明或正在出现活性,并概述了复发性AML儿童和青少年/年轻人的潜在治疗策略。
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引用次数: 0
Transdermal delivery of antibacterial peptides in the management of methicillin-resistant Staphylococcus aureus 经皮给药抗菌肽在耐甲氧西林金黄色葡萄球菌治疗中的应用
IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-06-19 DOI: 10.1016/j.coph.2025.102548
Shivraj Sangappa Shivpuje , Durgacharan A. Bhagwat , Pankaj Ashok Jadhav , Kimaya P. Joshi , Suraj N. Mali
Bacterial antimicrobial resistance (AMR) is of major public concern around the globe that arises when bacteria which earlier responded to the antibiotic therapy no longer respond to the same therapy and become resistant. The AMR has emerged due to the antibiotic abuse resulting in the development of multidrug-resistant (MDR) bacteria including methicillin-resistant Staphylococcus aureus (MRSA). The conventional antibiotics including vancomycin have nowadays become ineffective due to the gradual evolution and adaptation of bacteria to the surrounding environment. Antimicrobial peptides (AMPs) have emerged as an effective therapeutic option for the treatment of MRSA-induced skin and soft tissue infections (SSTIs). They offer broad-spectrum antibacterial activity with lower probability of drug resistance development. However, these AMPs face limitations such as proteolytic degradation, poor bioavailability, and potential cytotoxicity limiting their efficacy in clinical settings. Transdermal drug delivery platforms, including microneedles (MNs) coupled with the nano-formulations, have been developed to improve the AMP stability, bioavailability, and targeted release to avoid off-target cytotoxicity. Innovative strategies including Janus-type antibacterial dressings, bioresponsive MNs, and metal–organic frameworks (MOFs)-based nanocarriers have shown favorable results against the MRSA-induced skin infection. Numerous naturally occurring and synthetic antibacterial biopeptides and a Food and Drug Administration–approved glycopeptide, vancomycin, exhibited improved biofilm penetration and therapeutic efficacy when combined with smart MNs and nanosystems. Despite these improvements, challenges associated with AMP stability, cytotoxicity, and manufacturing costs still remain that limit its clinical translation. This review discussed the various MN-assisted deliveries of AMPs and associated challenges for the treatment of MRSA infections.
细菌抗菌素耐药性(AMR)是全球公众关注的主要问题,当先前对抗生素治疗有反应的细菌不再对同一治疗有反应并产生耐药性时,就会出现这种情况。抗生素耐药性的出现是由于抗生素滥用导致耐甲氧西林金黄色葡萄球菌(MRSA)等多重耐药(MDR)细菌的发展。由于细菌对周围环境的逐渐进化和适应,包括万古霉素在内的传统抗生素已经失效。抗菌肽(AMPs)已成为治疗mrsa诱导的皮肤和软组织感染(SSTIs)的有效治疗选择。它们具有广谱抗菌活性,耐药可能性较低。然而,这些amp面临着诸如蛋白水解降解、生物利用度差和潜在的细胞毒性等限制其临床疗效的局限性。经皮给药平台,包括微针(MNs)与纳米制剂的结合,已经被开发出来,以提高AMP的稳定性、生物利用度和靶向释放,以避免脱靶细胞毒性。包括janus型抗菌敷料、生物反应性MNs和基于金属有机框架(mof)的纳米载体在内的创新策略在对抗mrsa诱导的皮肤感染方面显示出良好的效果。许多天然存在和合成的抗菌生物肽以及美国食品和药物管理局批准的糖肽万古霉素,在与智能纳米网络和纳米系统结合时,表现出更好的生物膜渗透和治疗效果。尽管有这些改进,但与AMP稳定性、细胞毒性和制造成本相关的挑战仍然限制了其临床转化。这篇综述讨论了各种mn辅助AMPs的交付和MRSA感染治疗的相关挑战。
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引用次数: 0
Bioadhesive polymers in transdermal formulations for skin disorders 用于皮肤疾病的透皮配方中的生物粘合剂聚合物
IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-06-02 DOI: 10.1016/j.coph.2025.102544
Sanjeevani R. Desai , Durgacharan A. Bhagwat , Anil Kumar Singh , Rupali Baban Kumbhar , Jiyauddin Khan
Transdermal drug delivery (TDD) offer numerous advantages over conventional routes, including improved patient compliance and sustained drug release. Bioadhesive polymers play a crucial role in TDD, enhancing drug retention and controlled release. This review explores the applications of bioadhesive polymers in transdermal formulations for skin disorders, focusing on their adhesion mechanisms, structural modifications, and therapeutic potential. Natural bioadhesives like alginate and chitosan demonstrate anti-inflammatory, antimicrobial, and wound-healing properties, while synthetic polymers such as polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) offer controlled drug release and mechanical stability. Despite their advantages, challenges such as adhesion failure, moisture sensitivity, and limited macromolecular drug delivery persist. Recent innovations, including self-healing hydrogels, nanofiber-based transdermal systems, and enzymatic drug carriers, present new opportunities for dermatological applications.
经皮给药(TDD)提供了许多优于传统途径,包括提高患者依从性和持续的药物释放。生物黏附聚合物在TDD中起着至关重要的作用,增强了药物的保留和控释。本文综述了生物黏附聚合物在皮肤疾病透皮配方中的应用,重点介绍了它们的黏附机制、结构修饰和治疗潜力。海藻酸盐和壳聚糖等天然生物粘合剂具有抗炎、抗菌和伤口愈合的特性,而聚乙烯醇(PVA)和聚乙烯吡咯烷酮(PVP)等合成聚合物具有可控的药物释放和机械稳定性。尽管它们具有优势,但诸如粘附失败、水分敏感性和有限的大分子药物递送等挑战仍然存在。最近的创新,包括自修复水凝胶、纳米纤维透皮系统和酶促药物载体,为皮肤病学应用提供了新的机会。
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引用次数: 0
Advances in 3D-printed transdermal microneedle patches for antifungal therapy: Current scenario and challenges 用于抗真菌治疗的3d打印透皮微针贴片的进展:现状和挑战
IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-30 DOI: 10.1016/j.coph.2025.102545
Sarang Sunil Mahamuni , Madhuri Mahesh Desai , Koustubh Mansing Thorawades , Durgacharan A. Bhagwat
Skin fungal infection and systemic fungal infections are highly prevalent, causing significant healthcare burden. Addressing the pervasive and sometimes life-threatening nature of fungal infections has spurred extensive research into novel therapeutic strategies, particularly focusing on effective drug formulations and innovative delivery routes. Among this transdermal drug delivery (TDD) using microneedles (MNs) is a promising approach. 3D-printed MN patches are composed of arrays of tiny, needle-like structures engineered to facilitate the delivery of therapeutic agents by breaching the stratum corneum. Using the precision of 3D printing and improved drug delivery of MNs, 3D-printed transdermal MNs present a promising approach to manage fungal infections. This review provides a comprehensive analysis of recent literature on the use of 3D-printed MNs for antifungal therapy, emphasizing advancements in fabrication methods, drug incorporation techniques, and preclinical assessment outcomes. Furthermore, the study informs on various novel innovations employing antifungal agent administered through transdermal patches, demonstrating their efficacy and superiority over traditional methods. The majority of the studies are in vitro experimental studies, highlighting the need for human trials to translate 3D-printed MN-based TDD into clinical practice. The findings highlight the promise of 3D-printed microneedle patches in transforming transdermal antifungal therapy; however, extensive clinical validation remains crucial for regulatory endorsement and practical implementation.
皮肤真菌感染和全身真菌感染非常普遍,造成重大的医疗负担。针对真菌感染的普遍性和有时危及生命的性质,已经刺激了对新治疗策略的广泛研究,特别是关注有效的药物配方和创新的给药途径。其中,使用微针(MNs)的透皮给药(TDD)是一种很有前途的方法。3d打印MN贴片由微小的针状结构阵列组成,旨在通过破坏角质层来促进治疗剂的输送。利用3D打印的精度和改进的纳米颗粒的药物输送,3D打印透皮纳米颗粒提供了一种很有前途的治疗真菌感染的方法。这篇综述全面分析了最近关于3d打印MNs用于抗真菌治疗的文献,强调了制造方法、药物掺入技术和临床前评估结果的进展。此外,该研究还介绍了通过透皮贴片施用抗真菌剂的各种新颖创新,证明了它们比传统方法的有效性和优越性。大多数研究都是体外实验研究,强调了将3d打印的mn基TDD转化为临床实践的人体试验的必要性。这一发现强调了3d打印微针贴片在转化透皮抗真菌治疗方面的前景;然而,广泛的临床验证对于监管认可和实际实施仍然至关重要。
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引用次数: 0
Challenges in formulating transdermal systems for treating chronic skin infections 制定治疗慢性皮肤感染的透皮系统的挑战
IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-21 DOI: 10.1016/j.coph.2025.102540
Akshay Ramchandra Yadav , Shital Aniket Shinde , Shubhangi B. Sutar , Snehal Aditya Arvindekar , Dwi Marlina Syukri
Chronic skin infections, such as those caused by bacteria, viruses, and fungi compromise the skin's physical barrier, allowing microbial incursion, biofilm formation, and weakened immune response. This microbial assault disrupts skin hydration, and pH and induces inflammation, making it difficult for drug formulations to penetrate and manage the infection effectively. Traditional therapeutic strategies face hurdles like poor drug retention, systemic side effects, and antimicrobial resistance. Transdermal drug delivery systems (TDDS), on the other hand, offer localized and regulated drug release, decreasing systemic toxicity and improving bioavailability. However, physiological barriers, primarily the stratum corneum, limit the drug's capability to penetrate the deeper layers of the skin and necessitate the usage of permeation enhancers and advanced formulation techniques. Physicochemical barriers of the drug, including high molecular weight, lipophilicity, and solubility, also hamper transdermal drug absorption. Additionally, issues related to drug stability, release kinetics, and adhesive matrices affect drug retention, controlled release, and therapeutic efficacy in the infected skin, which might be compromised due to ulceration, hyperkeratosis, or excessive irritation. Novel strategies such as nanocarrier-based TDDS including liposomes, nanoparticles, and microneedles potentially improve drug permeation and bioavailability while treating chronic skin infections. Nevertheless, the challenges remain in adjusting the compatibility of the drug formulations with the infected skin, while maintaining its effectiveness. This review is a comprehensive look at the physiological and formulation challenges in TDDS for managing chronic skin infections. More real-world evidence is required to further refine TDDS formulations for improved permeation, stability, and clinical efficacy against chronic skin infections.
慢性皮肤感染,如由细菌、病毒和真菌引起的感染,会破坏皮肤的物理屏障,使微生物侵入,形成生物膜,削弱免疫反应。这种微生物的攻击破坏了皮肤的水合作用和pH值,并引起炎症,使药物配方难以渗透和有效地控制感染。传统的治疗策略面临着诸如药物潴留不良、全身副作用和抗菌素耐药性等障碍。另一方面,透皮给药系统(TDDS)提供局部和可调节的药物释放,降低全身毒性并提高生物利用度。然而,生理障碍,主要是角质层,限制了药物穿透皮肤深层的能力,需要使用渗透增强剂和先进的配方技术。药物的物理化学屏障,包括高分子量、亲脂性和溶解度,也阻碍药物经皮吸收。此外,与药物稳定性、释放动力学和粘附基质相关的问题影响药物在感染皮肤中的保留、控制释放和治疗效果,这可能由于溃疡、角化过度或过度刺激而受到损害。新策略,如基于纳米载体的TDDS,包括脂质体、纳米颗粒和微针,在治疗慢性皮肤感染时可能改善药物渗透和生物利用度。然而,在调整药物配方与受感染皮肤的相容性,同时保持其有效性方面仍然存在挑战。本文综述了TDDS治疗慢性皮肤感染的生理和配方挑战。需要更多的实际证据来进一步完善TDDS配方,以提高渗透性、稳定性和抗慢性皮肤感染的临床疗效。
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引用次数: 0
Editorial overview: Advanced therapies and new targets in ocular diseases 编辑综述:眼部疾病的先进疗法和新靶点
IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-17 DOI: 10.1016/j.coph.2025.102543
Claudio Bucolo, Chiara M. Eandi, Sanjoy K. Bhattacharya
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引用次数: 0
Lipid-based nanocarriers in topical applications for skin infections 脂基纳米载体在皮肤感染的局部应用
IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-16 DOI: 10.1016/j.coph.2025.102541
Monali M. Upare , Koustubh Mansing Thorawade , Abhay Prakash Mishra , Manisha Nigam , Neti Waranuch
Skin infections are a significant healthcare issue, particularly with rising AMR. LBNs like liposomes, SLNs, and NLCs hold promise for enhancing topical drug delivery in treating skin infections. They improve solubility, stability, and sustained release of antimicrobial agents, allowing deeper skin penetration. Their biocompatibility and ability to encapsulate various drugs make them effective against bacterial and fungal infections. However, challenges such as stability issues (aggregation, fusion, sedimentation, and oxidation), regulatory hurdles (lack of specific guidelines), and manufacturing scalability limit their clinical use. This article reviews the benefits, advancements, and challenges of lipid-based nanocarriers for treating skin infections through topical delivery.
皮肤感染是一个重要的医疗问题,特别是随着抗生素耐药性的上升。脂质体、sln和NLCs等lbn有望在治疗皮肤感染时增强局部药物输送。它们改善了抗菌剂的溶解度、稳定性和持续释放,允许更深的皮肤渗透。它们的生物相容性和包封各种药物的能力使它们对细菌和真菌感染有效。然而,诸如稳定性问题(聚集、融合、沉淀和氧化)、监管障碍(缺乏具体指南)和制造可扩展性等挑战限制了它们的临床应用。本文综述了脂基纳米载体通过局部递送治疗皮肤感染的益处、进展和挑战。
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引用次数: 0
Advanced microneedle arrays for transdermal antibiotic delivery 用于经皮给药的先进微针阵列
IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-15 DOI: 10.1016/j.coph.2025.102542
Vishin Patil , Pooja S. Patil , Mugdha Vasant Kulkarni , Suraj Nijamso Pattekari , Zamir G. Khan
Traditional antibiotic delivery methods face limitations including, systemic toxicity and poor bioavailability. Transdermal microneedle (MN) arrays bypass skin barriers, enhancing antibiotic penetration while minimizing resistance risks. This review examines advanced MN systems such as solid, coated, hollow, dissolvable, and smart stimuli-responsive, highlighting design innovations, nanomaterial integration, and preclinical efficacy against infections like methicillin-resistant Staphylococcus aureus (MRSA). While MN technology enables targeted, minimally invasive delivery, clinical adoption requires overcoming scalability hurdles and demonstrating real-world efficacy. Comprehensive clinical validation remains essential to translate these systems into mainstream solutions for combating antibiotic resistance and improving chronic wound management.
传统的抗生素给药方法存在局限性,包括全身毒性和生物利用度差。透皮微针(MN)阵列绕过皮肤屏障,增强抗生素渗透,同时最大限度地降低耐药风险。本文综述了先进的MN系统,如固体、涂层、空心、可溶解和智能刺激反应,强调了设计创新、纳米材料集成和抗耐甲氧西林金黄色葡萄球菌(MRSA)感染的临床前疗效。虽然MN技术可以实现有针对性的微创输送,但临床应用需要克服可扩展性障碍并证明实际疗效。全面的临床验证对于将这些系统转化为对抗抗生素耐药性和改善慢性伤口管理的主流解决方案仍然至关重要。
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引用次数: 0
Allogeneic double-negative T-cell therapy for acute myeloid leukemia 异基因双阴性t细胞治疗急性髓性白血病
IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-10 DOI: 10.1016/j.coph.2025.102537
Enoch Tin , Jongbok Lee , Li Zhang
CD3+CD4CD8 double-negative T cells (DNTs) represent a unique subset of T lymphocytes with potent cytotoxicity against acute myeloid leukemia (AML). Importantly, allogeneic DNTs do not induce graft-versus-host disease and have demonstrated characteristics suitable for off-the-shelf cellular therapy with promising efficacy in early-stage clinical trials. DNT therapy can synergize with conventional AML treatments and can be transduced with chimeric antigen receptors (CARs). Notably, persistent CAR+ T cells in patients, who achieved long-term remission, predominantly have a DNT phenotype. The unique and versatile therapeutic properties of allogeneic DNTs position them as a strong candidate among adoptive cellular therapies for AML.
CD3+CD4−CD8−双阴性T细胞(DNTs)是一种独特的T淋巴细胞亚群,对急性髓性白血病(AML)具有强大的细胞毒性。重要的是,同种异体DNTs不会诱导移植物抗宿主病,并且在早期临床试验中显示出适合现成细胞治疗的特性,具有良好的疗效。DNT治疗可以与传统的AML治疗协同,并且可以用嵌合抗原受体(car)转导。值得注意的是,在获得长期缓解的患者中,持续性CAR+ T细胞主要具有DNT表型。同种异体DNTs独特而多功能的治疗特性使其成为AML过继细胞疗法的有力候选。
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引用次数: 0
Colloidal drug delivery systems for infectious diseases of skin 皮肤传染病用胶体给药系统
IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-10 DOI: 10.1016/j.coph.2025.102536
Sopan Nangare , Varda Joshi , Shrikant Magdum , Riya Patil , Vishin Patil
Infectious skin diseases represent a major global health burden, demanding effective and affordable treatments. Conventional therapies often face challenges such as reduced bioavailability, enzymatic degradation, low permeability, and poor solubility. Colloidal-based transdermal drug delivery systems, including liposomes, ethosomes, niosomes, nanoemulsions, polymeric nanoparticles, micelles, solid lipid nanoparticles, etc., have emerged as promising alternatives. In brief, these colloidal systems enhance drug penetration, stability, biocompatibility, and customized release while improving antimicrobial efficacy against various pathogens and minimizing systemic side effects. In conclusion, colloidal formulations offer a targeted, efficient approach, optimizing therapeutic outcomes, improving patient compliance, and advancing the treatment of infectious skin diseases.
传染性皮肤病是全球主要的健康负担,需要有效和负担得起的治疗。传统疗法经常面临生物利用度降低、酶降解、渗透性低和溶解度差等挑战。基于胶体的透皮给药系统,包括脂质体、脂质体、乳质体、纳米乳液、聚合纳米颗粒、胶束、固体脂质纳米颗粒等,已经成为有希望的替代方案。简而言之,这些胶体系统增强了药物的渗透、稳定性、生物相容性和定制释放,同时提高了对各种病原体的抗菌功效,并最大限度地减少了全身副作用。总之,胶体制剂提供了一种有针对性的、有效的方法,优化了治疗结果,提高了患者的依从性,并推进了传染性皮肤病的治疗。
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引用次数: 0
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