Advanced drug delivery reviews最新文献_第3页

Emerging nanoparticle-based therapies for pancreatic cancer: Current clinical landscape 新兴的基于纳米颗粒的胰腺癌治疗方法：目前的临床前景

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-12 DOI: 10.1016/j.addr.2025.115760

Ainara Salgado-Pascual , Sara Zalba , Juan José Lasarte , Maria J. Garrido

Pancreatic cancer, particularly ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal subtypes due to late diagnosis, the absence of early biomarkers, and the presence of a complex tumor microenvironment (TME). This TME is characterized by a dense desmoplastic stroma, hypovascularization, immunosuppression, and an acidic extracellular pH. All of these factors hinder the delivery and efficacy of conventional therapies, especially in advanced stages.

Nanoparticles (NPs), including liposomes, polymeric micelles, albumin-bound particles and lipid nanoparticles, have emerged as a promising tool for overcoming TME barriers, and enhance drug delivery in tumor while minimizing systemic toxicity. NPs can exploit mechanisms such as the Enhanced Permeability and Retention (EPR) effect and active targeting. Clinically approved NPs such as Nab-Paclitaxel and liposomal Irinotecan have demonstrated improved pharmacokinetics and therapeutic benefits in PDAC. Furthermore, ongoing clinical trials are exploring novel NP-based strategies such as gene delivery, radiosensitization, immunomodulation and ferroptosis induction. Despite these promising advances, significant challenges remain, including poor tumor penetration, heterogeneity in EPR, and immune recognition of NPs leading to their clearance from bloodstream before reaching the tumor. Innovative solutions such as biomimetic coatings, stimuli-responsive systems and personalized formulations, are being evaluated to enhance NP performance. Standardization of NP characterization and data reporting are essential to accelerating clinical translation. The integration of artificial intelligence and machine learning could further optimize NP design and patient stratification. Overall, nanotechnology represents a crucial frontier of research for developing more effective and personalized pancreatic cancer treatments.

胰腺癌，特别是导管腺癌（PDAC）是最具侵袭性和致死性的亚型之一，由于诊断较晚，缺乏早期生物标志物，以及存在复杂的肿瘤微环境（TME）。这种TME的特征是致密的间质、低血管化、免疫抑制和酸性细胞外ph。所有这些因素都阻碍了常规治疗的传递和疗效，特别是在晚期。纳米颗粒（NPs），包括脂质体、聚合物胶束、白蛋白结合颗粒和脂质纳米颗粒，已经成为克服TME障碍、增强肿瘤药物传递同时最小化全身毒性的有前途的工具。NPs可以利用增强渗透性和保留性（EPR）效应和主动靶向等机制。临床批准的NPs，如nab -紫杉醇和伊立替康脂质体，已经证明改善了PDAC的药代动力学和治疗效果。此外，正在进行的临床试验正在探索新的基于np的策略，如基因传递、放射增敏、免疫调节和铁下垂诱导。尽管取得了这些有希望的进展，但仍然存在重大挑战，包括肿瘤穿透性差、EPR的异质性以及NPs的免疫识别导致其在到达肿瘤之前从血液中清除。人们正在评估诸如仿生涂层、刺激响应系统和个性化配方等创新解决方案，以提高NP性能。NP表征和数据报告的标准化对于加速临床翻译至关重要。人工智能和机器学习的结合可以进一步优化NP设计和患者分层。总的来说，纳米技术代表了研究开发更有效和个性化的胰腺癌治疗的关键前沿。

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引用次数: 0

Exploiting colloidal drug aggregation for drug delivery: From promise to prediction using computational tools 利用胶体药物聚集给药：从使用计算工具的承诺到预测

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-11 DOI: 10.1016/j.addr.2025.115758

Kai V. Slaughter , Xiang Olivia Li , Molly S. Shoichet

Colloidal drug aggregates are amorphous nanoparticles formed by the self-assembly of hydrophobic small molecule drugs. They can be leveraged as drug-rich nanoparticle formulations for drug delivery. However, it is difficult to predict which drugs will form colloidal aggregates, which stabilizers will be effective, and what the in vivo fate of the nanoparticles will be. These challenges can be addressed, in part, with computational tools including artificial intelligence such as machine learning. Molecular dynamics simulations have been used to improve our understanding of the intermolecular forces that govern the assembly of colloidal drug aggregates. Several predictive tools exist to identify aggregators, but these are typically used to eliminate aggregators from screening libraries rather than design drug delivery formulations. Colloidal drug aggregates require stabilizers to prevent particle growth and precipitation. Computational analyses have been used to predict which colloidal drug aggregators can be stabilized by a particular small molecule excipient and to identify drug-stabilizer pairs. Successful stabilization has enabled colloidal drug aggregate evaluation for applications such as nanomedicine and sustained release. Additionally, certain colloid-forming drugs can be useful for co-delivery of nucleic acids. In future studies, computational tools can be developed to predict the biological activity of colloidal drug aggregates, building upon other approaches currently used for lipid nanoparticles and other modalities. Ultimately, leveraging computational strategies to improve the design of colloidal drug aggregates can help realize the potential of this high drug-loading delivery platform.

胶体药物聚集体是由疏水小分子药物自组装形成的无定形纳米颗粒。它们可以作为富含药物的纳米颗粒配方用于药物输送。然而，很难预测哪些药物会形成胶体聚集体，哪些稳定剂会有效，以及纳米颗粒在体内的命运如何。这些挑战可以部分地通过包括机器学习等人工智能在内的计算工具来解决。分子动力学模拟已被用于提高我们对控制胶体药物聚集体组装的分子间力的理解。有几种预测工具可以识别聚合器，但这些工具通常用于从筛选库中消除聚合器，而不是设计给药配方。胶体药物聚集体需要稳定剂来防止颗粒生长和沉淀。计算分析已经被用来预测哪些胶体药物聚集剂可以被特定的小分子赋形剂稳定，并识别药物稳定剂对。成功的稳定使胶体药物聚集体的应用评估，如纳米医学和缓释。此外，某些形成胶体的药物可用于核酸的共递送。在未来的研究中，可以开发计算工具来预测胶体药物聚集体的生物活性，以目前用于脂质纳米颗粒和其他模式的其他方法为基础。最终，利用计算策略来改进胶体药物聚集体的设计可以帮助实现这种高载药递送平台的潜力。

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引用次数: 0

Overcoming barriers and shaping the future: Challenges and innovations in nucleic acid therapies for Glioblastoma 克服障碍，塑造未来：胶质母细胞瘤核酸治疗的挑战与创新

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-10 DOI: 10.1016/j.addr.2025.115759

Alaa Zam , Nadia Rouatbi , Adam A. Walters , Khuloud T. Al-Jamal

Glioblastoma (GBM) is the most aggressive and treatment-resistant primary brain tumor in adults. Conventional therapies offer limited benefit due to the tumor's heterogeneity, invasive nature, and the presence of the blood–brain barrier, which restricts therapeutic access. Nucleic acid (NA)-based therapies, including small interfering RNA, microRNA, antisense oligonucleotides, splice-switching oligonucleotides, and CRISPR-based systems, have emerged as promising tools to modulate oncogenic pathways and overcome resistance mechanisms at the genetic level. However, effective delivery remains the primary challenge in translating these therapies into clinical success. This review examines the current landscape of NA-based strategies for GBM, with a focus on innovative delivery systems designed to navigate biological barriers and enhance therapeutic precision. We highlight clinical progress made with nanocarrier platforms such as liposomes, lipid nanoparticles, and exosome-based systems, and evaluate their safety, specificity, and delivery efficiency. Additionally, we discuss the most promising preclinical advances, including multifunctional, targeted, and stimuli-responsive carriers, that demonstrate strong potential for clinical translation. Our analysis underscores that the therapeutic efficacy of NA approaches in GBM is inseparable from the sophistication of their delivery platforms. Moving forward, the integration of rationally designed carriers with gene-targeted payloads holds the key to unlocking the full potential of precision medicine in GBM.

胶质母细胞瘤（GBM）是成人中最具侵袭性和治疗耐药性的原发性脑肿瘤。由于肿瘤的异质性、侵袭性和血脑屏障的存在，限制了治疗途径，传统疗法的疗效有限。基于核酸（NA）的治疗，包括小干扰RNA、微RNA、反义寡核苷酸、剪接开关寡核苷酸和基于crispr的系统，已经成为在遗传水平上调节致癌途径和克服耐药机制的有前途的工具。然而，有效的递送仍然是将这些疗法转化为临床成功的主要挑战。本文综述了目前基于na的GBM治疗策略，重点关注旨在克服生物屏障和提高治疗精度的创新给药系统。我们强调了纳米载体平台（如脂质体、脂质纳米颗粒和外泌体系统）的临床进展，并评估了它们的安全性、特异性和递送效率。此外，我们还讨论了最有希望的临床前进展，包括多功能、靶向和刺激反应性载体，这些载体显示出强大的临床转化潜力。我们的分析强调NA入路治疗GBM的疗效与其输送平台的复杂性密不可分。展望未来，整合合理设计的载体与基因靶向有效载荷是释放GBM精准医疗全部潜力的关键。

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引用次数: 0

Engineering tumor spatial heterogeneity in vitro 体外工程肿瘤空间异质性

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-10 DOI: 10.1016/j.addr.2025.115757

Changchong Chen , Zixuan Zhao , Dong Hua Seah , Kenny Zhuoran Wu , Senthilkumar Mohanaselvi , Eliza Li Shan Fong

Spatial heterogeneity is a fundamental feature of the tumor microenvironment, characterized by structured variations in cellular composition, phenotypic states, extracellular matrix (ECM) organization, and biochemical and biophysical gradients. These spatial patterns shape tumor evolution, modulate immune infiltration, and underlie resistance to therapy. Advances in spatial transcriptomics and multiplex imaging have revealed dynamic and region-specific niches, such as hypoxic cores, immune-excluded zones, and fibroblast-dense invasive fronts, that correlate with clinical outcomes. However, most in vitro models fail to capture this architectural complexity. Recent engineering technologies, including 3D bioprinting, organoid assembloids, organ-on-a-chip systems, and ECM-mimetic scaffolds, now enable controlled reconstruction of tumor spatial organization and microregional heterogeneity. These technologies allow integration of patient-derived cells, tunable matrix environments, and spatially defined signaling to mimic in vivo pathophysiology. When integrated with spatial transcriptomics and proteomics, these models enable mechanistic exploration of microregional tumor biology, evaluation of therapeutic responses, and investigation of immunotherapy resistance. This review integrates our current understanding of spatial heterogeneity in cancer with enabling engineering strategies to guide future developments in tumor biology and therapeutic innovation.

空间异质性是肿瘤微环境的一个基本特征，其特征是细胞组成、表型状态、细胞外基质（ECM）组织以及生化和生物物理梯度的结构性变化。这些空间模式塑造肿瘤的演变，调节免疫浸润，并对治疗产生抵抗。空间转录组学和多重成像技术的进步揭示了与临床结果相关的动态和区域特异性生态位，如缺氧核心、免疫排斥区和成纤维细胞密集侵入前沿。然而，大多数体外模型无法捕获这种架构复杂性。最近的工程技术，包括3D生物打印、类器官组装体、器官芯片系统和模拟ecm支架，现在可以控制肿瘤空间组织和微区域异质性的重建。这些技术允许整合患者来源的细胞、可调节的基质环境和空间定义的信号来模拟体内病理生理。当与空间转录组学和蛋白质组学相结合时，这些模型可以对微区域肿瘤生物学进行机制探索，评估治疗反应，并研究免疫治疗耐药性。这篇综述将我们目前对癌症空间异质性的理解与工程策略结合起来，以指导肿瘤生物学和治疗创新的未来发展。

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引用次数: 0

Integrating PROTAC-based targeted protein degradation with nanodelivery systems to overcome cancer therapeutic resistance 整合基于protac的靶向蛋白降解与纳米递送系统克服癌症治疗耐药性

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-10 DOI: 10.1016/j.addr.2025.115755

Xinyu Gou , Shi He , Bilan Wang , Lingli Zhang , Yongzhong Cheng , Xiang Gao

Tumor drug resistance is a major challenge in cancer treatment, as traditional chemotherapeutic agents and small molecule inhibitors often become ineffective in targeting tumors due to drug resistance. Proteolysis Targeting Chimeras (PROTAC) technology, as a novel protein degradation method, provides a new insight into overcoming drug resistance in tumors with the assistance of nanodelivery systems. PROTAC is able to degrade rather than merely inhibit tumor-associated proteins, thus avoiding drug resistance caused by gene mutations, protein overexpression and conformational changes, demonstrating significant advantages in overcoming tumor resistance. First, PROTAC eliminates the biological activity of the target protein by directly degrading it, thus overcoming the limitation of traditional inhibitors, which are susceptible to mutations of the structure and activity of the target protein. Second, PROTAC molecules are highly versatile and flexible, and can target proteins that are difficult to target with conventional drugs, including enzymatically inactive proteins, transcription factors and oncogenic protein complexes. In addition, PROTAC technology, with the booster of nanodelivery systems, can effectively improve solubility and bioavailability, enhance targeting and delivery efficiency while improving its stability, and can be combined with other therapeutic methods to further enhance the therapeutic effect. The versatility of PROTAC makes it a highly promising option for overcoming tumor drug resistance, and their effectiveness has been validated in a variety of cancers, including breast cancer, prostate cancer, and leukemia. In this paper, we will review the recent progress of PROTAC technology in overcoming tumor drug resistance and briefly summarize the advantages and challenges of PROTAC technology combined with nanodelivery system, hoping to provide valuable references for researchers in related fields.

肿瘤耐药是肿瘤治疗的主要挑战，传统的化疗药物和小分子抑制剂往往由于耐药而无法靶向肿瘤。蛋白质水解靶向嵌合体（Proteolysis Targeting Chimeras， PROTAC）技术作为一种新的蛋白质降解方法，为利用纳米递送系统克服肿瘤耐药提供了新的思路。PROTAC能够降解而不仅仅是抑制肿瘤相关蛋白，从而避免了基因突变、蛋白过表达和构象改变引起的耐药，在克服肿瘤耐药方面具有显著优势。首先，PROTAC通过直接降解目标蛋白来消除其生物活性，从而克服了传统抑制剂易受目标蛋白结构和活性突变的限制。其次，PROTAC分子具有高度的通用性和灵活性，可以靶向传统药物难以靶向的蛋白质，包括酶失活蛋白、转录因子和致癌蛋白复合物。此外，PROTAC技术在纳米递送系统的助推下，可有效提高溶解度和生物利用度，在提高稳定性的同时增强靶向性和递送效率，并可与其他治疗方法联合使用，进一步提高治疗效果。PROTAC的多功能性使其成为克服肿瘤耐药性的极有希望的选择，其有效性已在多种癌症中得到验证，包括乳腺癌，前列腺癌和白血病。本文将综述PROTAC技术在克服肿瘤耐药方面的最新进展，并简要总结PROTAC技术结合纳米给药系统的优势和挑战，希望为相关领域的研究人员提供有价值的参考。

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引用次数: 0

Gas-based therapeutics and delivery platforms in cancer immunotherapy 肿瘤免疫治疗中的气体疗法和输送平台

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-06 DOI: 10.1016/j.addr.2025.115746

Van-Anh Thi Nguyen , Chieh-Cheng Huang , Yunching Chen

Gas-based therapeutics are emerging as a promising strategy in cancer immunotherapy. Small gaseous signaling molecules such as nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and oxygen (O₂) efficiently penetrate tumor tissues and modulate diverse immune pathways. These therapeutic gases can relieve tumor hypoxia, enhance immune cell infiltration, induce immunogenic cancer cell death, and suppress immunosuppressive signaling within the tumor microenvironment (TME). Therefore, they potentiate immune checkpoint blockade and other immunotherapies while overcoming key barriers to immune evasion. Despite this promise, the clinical translation of gas-based therapies faces significant challenges, including short half-lives, systemic toxicity, and lack of spatiotemporal control. To address these limitations, a variety of delivery platforms have been developed—from nanocarriers and injectable hydrogels to inhalable and oral prodrug formulations and stimuli-responsive systems—that enable safe, tumor-targeted, and controlled release of therapeutic gases. Such engineered strategies maximize antitumor efficacy while minimizing off-target effects. This review highlights the immunomodulatory roles of therapeutic gases, examines state-of-the-art delivery technologies, and discusses how these advances lay the foundation for precision gas immunotherapy to unlock the clinical potential of gaseous immunomodulators in cancer treatment.

基于气体的治疗方法正在成为一种有前景的癌症免疫治疗策略。小的气体信号分子如一氧化氮（NO）、一氧化碳（CO）、硫化氢（H2S）和氧（O2）有效地渗透肿瘤组织并调节多种免疫途径。这些治疗气体可以缓解肿瘤缺氧，增强免疫细胞浸润，诱导免疫原性癌细胞死亡，抑制肿瘤微环境（tumor microenvironment， TME）内的免疫抑制信号。因此，它们增强了免疫检查点封锁和其他免疫疗法，同时克服了免疫逃避的关键障碍。尽管前景光明，但气体疗法的临床转化面临着重大挑战，包括半衰期短、全身毒性和缺乏时空控制。为了解决这些限制，已经开发了各种递送平台-从纳米载体和可注射水凝胶到可吸入和口服前药制剂和刺激反应系统-使治疗气体的安全，肿瘤靶向和控制释放。这种工程策略最大限度地提高了抗肿瘤效果，同时最大限度地减少了脱靶效应。这篇综述强调了治疗气体的免疫调节作用，检查了最先进的输送技术，并讨论了这些进步如何为精确气体免疫治疗奠定基础，以释放气体免疫调节剂在癌症治疗中的临床潜力。

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引用次数: 0

Clinical translation and landscape of superparamagnetic iron oxide nanoparticles 超顺磁性氧化铁纳米颗粒的临床转化和景观

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-06 DOI: 10.1016/j.addr.2025.115756

Yanchen Li, Roman A. Barmin, Rui Zhang, Fabian Kiessling, Twan Lammers, Roger M. Pallares

Since their initial clinical approval as liver imaging agents nearly three decades ago, superparamagnetic iron oxide nanoparticles (SPIONs) have evolved beyond diagnostic imaging to include also therapeutic and theranostic applications. Their clinical utility in both diagnosis and therapy depends on a combination of intrinsic physicochemical properties and in vivo behaviors, such as biodistribution and pharmacokinetics. These attributes enable specific applications, depending on the mechanisms of action and route of administration. For example, nanoparticle degradation can support anemia treatments. Tissue-specific retention in fenestrated organs and pathological tissues after systemic administration allows for imaging of the liver and inflammation sites, and image-guided therapy. Local delivery enables applications such as sentinel lymph node mapping and localized tumor thermal ablation. At the same time, these properties also constrain SPIONs from broader use as universal nanodiagnostic and theranostic agents. This review provides an overview of the current clinical landscape of superparamagnetic iron oxide nanoparticles, identifies shared features that have facilitated their successful translation, and discusses the critical challenges that must be addressed to enable wider clinical adoption.

超顺磁性氧化铁纳米颗粒（SPIONs）自近30年前首次被临床批准为肝脏显像剂以来，已经从诊断性成像发展到治疗性和治疗性应用。它们在诊断和治疗中的临床应用取决于内在的物理化学性质和体内行为的结合，如生物分布和药代动力学。这些属性启用特定的应用程序，具体取决于操作机制和管理路径。例如，纳米颗粒降解可以支持贫血治疗。系统给药后，组织特异性滞留在开窗器官和病理组织中，可以对肝脏和炎症部位进行成像，并进行图像引导治疗。局部递送使前哨淋巴结定位和局部肿瘤热消融等应用成为可能。同时，这些特性也限制了SPIONs作为通用纳米诊断和治疗药物的广泛应用。这篇综述概述了超顺磁性氧化铁纳米颗粒目前的临床前景，确定了促进其成功转化的共同特征，并讨论了必须解决的关键挑战，以使其更广泛的临床应用。

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引用次数: 0

Perspectives and trends in gas delivery systems based on ultrasound responsive nanomaterials for cancer therapy 基于超声响应纳米材料的气体输送系统用于癌症治疗的前景和趋势

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-04 DOI: 10.1016/j.addr.2025.115747

Jooho Moon , Hanhee Cho , Jeonghun Yu , Hyuncheol Kim , Kwangmeyung Kim

Gas-based therapeutic strategies (e.g., nitric oxide and carbon dioxide delivery) have shown promising potential for modulating the tumor microenvironment and enhancing anticancer efficacy. However, their clinical translation is limited by their poor spatiotemporal control, systemic toxicity, and limited tumor selectivity. As a powerful alternative, nanomaterial-based gas delivery systems offer improved stability, targeted accumulation, and programmable release in response to tumor-specific stimuli. Among various triggering methods, ultrasound has received particular attention because of its noninvasive nature, deep tissue penetration, and ability to locally activate nanocarriers. This review highlights the recent advances in ultrasound-triggered gas-generating delivery systems, including their design principles, gas-generating mechanisms, and representative nanoplatforms. The mechanistic insights into ultrasound-induced cavitation, thermal effects, and sonodynamic activation are discussed in the context of controlled gas release and drug delivery. Moreover, the therapeutic applications of these systems in solid tumors and metastatic lesions are summarized, and combination strategies integrating ultrasound-triggered gas release with chemotherapy, immunotherapy, or phototherapy are outlined. Finally, the current challenges and future perspectives for clinical translation are addressed, focusing on improving safety, scalability, and patient-specific tailoring. Ultrasound-responsive gas-generating delivery systems represent a promising approach for spatiotemporally controlled cancer therapy.

基于气体的治疗策略（例如，一氧化氮和二氧化碳输送）在调节肿瘤微环境和增强抗癌功效方面显示出良好的潜力。然而，它们的临床转化受到其较差的时空控制、全身毒性和有限的肿瘤选择性的限制。作为一种强大的替代方案，基于纳米材料的气体输送系统提供了更好的稳定性、靶向积累和可编程释放，以响应肿瘤特异性刺激。在各种触发方法中，超声因其非侵入性、深入组织和局部激活纳米载体的能力而受到特别关注。本文综述了超声触发产气输送系统的最新进展，包括其设计原理、产气机制和代表性纳米平台。在受控气体释放和药物传递的背景下，讨论了超声诱导空化、热效应和声动力激活的机理。此外，总结了这些系统在实体瘤和转移性病变中的治疗应用，并概述了将超声触发气体释放与化疗、免疫治疗或光疗相结合的联合策略。最后，讨论了临床翻译目前面临的挑战和未来的前景，重点是提高安全性、可扩展性和针对患者的定制。超声响应气体产生输送系统代表了一种有前途的方法，用于时空控制癌症治疗。

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引用次数: 0

Recent advances in numerical simulation of magnetically guided drug delivery systems and applications 磁导给药系统数值模拟及其应用的最新进展

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-04 DOI: 10.1016/j.addr.2025.115745

Zhenyang Xu , Tayebeh Mousavi , Xiaoli Liu , Anita Ahmadi Birjandi , Maya Thanou , Haiming Fan , Mark Ainslie

Magnetically guided drug delivery (MGDD) employs magnetic forces acting on magnetically responsive drug delivery systems (DDS) to direct therapeutic agents toward diseased regions, thereby enhancing local drug accumulation while minimising systemic side effects. Numerical simulation, grounded in the physical principles governing MGDD, provides an efficient computational framework for modelling and visualising these processes, thereby accelerating progress in MGDD research. This review comprehensively summarises recent advances in the application of numerical simulation to MGDD, including magnet design and analysis, multiscale modelling of DDS transport processes at macroscopic, mesoscopic, and microscopic scales, and DDS design and evaluation. In addition, the integration of optimisation algorithms and artificial intelligence (AI) with numerical simulation for MGDD is discussed. Finally, future perspectives are presented, emphasising the development of high-fidelity, multiscale, and AI-driven simulation frameworks to accelerate clinical translation toward personalised, efficient MGDD-based therapeutic systems.

磁导给药（MGDD）利用磁力作用于磁响应药物给药系统（DDS），将治疗剂导向病变区域，从而增强局部药物积累，同时最大限度地减少全身副作用。数值模拟以控制MGDD的物理原理为基础，为这些过程的建模和可视化提供了有效的计算框架，从而加速了MGDD研究的进展。本文综述了近年来数值模拟技术在磁体设计与分析、DDS输运过程宏观、介观和微观多尺度模拟、DDS设计与评价等方面的研究进展。此外，还讨论了优化算法和人工智能（AI）与MGDD数值模拟的集成。最后，提出了未来的展望，强调高保真、多尺度和人工智能驱动的模拟框架的发展，以加速向个性化、高效的基于mddd的治疗系统的临床转化。

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引用次数: 0

GMP-compliant manufacturing of iPSC-derived therapeutic cell products: Technologies, applications, risks and limitations ipsc衍生治疗细胞产品的gmp合规生产：技术、应用、风险和限制

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2025-12-02 DOI: 10.1016/j.addr.2025.115744

Alexandra Haase, Arjang Ruhparwar, Ulrich Martin

The development of induced pluripotent stem cells (iPSCs) has transformed the field of regenerative medicine. However, to use iPSCs for therapeutic applications, iPSC-based products must be produced under Good Manufacturing Practice (GMP) conditions. This process involves reprogramming somatic cells, characterizing and banking iPSC lines, introducing therapeutic transgenes if necessary, and scaling up cell expansion and differentiation for clinical use. This review provides an overview of the relevant regulatory authorities and relevant regulations in the US, Europe, and Japan. It also discusses the current challenges and opportunities in producing GMP-compliant iPSCs. These challenges include the need for defined culture media, as well as developing all the required GMP-compliant processes, such as reprogramming, establishing iPSC clones, and manufacturing processes that lead to the final advanced therapy medicinal product (ATMP). For autologous products in particular, this can be complicated by cell line-specific variation of proliferation velocity and differentiation biases. The review also discusses attempts to develop automated closed systems. It emphasizes the importance of ensuring the sterility, identity, (epi)genetic integrity, and functionality of the final cell products to guarantee the safety and the efficacy of iPSC-based therapies. However, the need for reproducibility, rigorous quality control and safety requirements has resulted in high regulatory hurdles and extremely high costs, which often prevent the initiation of clinical trials. Overcoming these challenges will enable iPSCs to play an integral role in future medicine and offer new treatment options for various diseases.

诱导多能干细胞（iPSCs）的发展已经改变了再生医学领域。然而，要将ipsc用于治疗应用，基于ipsc的产品必须在良好生产规范（GMP）条件下生产。这一过程包括对体细胞进行重编程，鉴定和储存iPSC系，必要时引入治疗性转基因，扩大细胞扩增和分化以供临床使用。本综述概述了美国、欧洲和日本的相关监管机构和相关法规。它还讨论了生产符合gmp的iPSCs的当前挑战和机遇。这些挑战包括需要明确的培养基，以及开发所有必需的符合gmp的流程，例如重编程，建立iPSC克隆，以及导致最终先进治疗药物产品（ATMP）的制造流程。特别是对于自体产物，这可能会因细胞系特异性增殖速度和分化偏差的变化而变得复杂。该评论还讨论了开发自动化封闭系统的尝试。它强调了确保最终细胞产品的无菌性、身份、（epi）遗传完整性和功能的重要性，以确保基于ipsc的治疗的安全性和有效性。然而，对可重复性、严格的质量控制和安全要求的需要导致了很高的监管障碍和极高的成本，这往往阻碍了临床试验的开展。克服这些挑战将使多能干细胞在未来医学中发挥不可或缺的作用，并为各种疾病提供新的治疗选择。

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