International Journal of Pharmaceutics: X最新文献_第2页

Ligand-modified liposomes as drug delivery systems for the active targeting of pancreatic cancer 配体修饰脂质体作为主动靶向胰腺癌的药物递送系统

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2026-01-02 DOI: 10.1016/j.ijpx.2026.100483

Yerin Jang , Jaehee Jang , Jaewoo Son , Hee-Young Lee , Jonghoon Choi

Pancreatic cancer is among the most fatal malignancies worldwide. The aggressive nature of this disease, coupled with late-stage diagnosis and limited therapeutic options, highlights the urgent need for innovative treatment approaches. Targeted therapy has emerged as a promising strategy to enhance therapeutic efficacy while minimizing systemic toxicity. Liposomes, as versatile nanoparticles, have shown significant potential to contribute to the develpment of drug delivery system. These lipid-based vesicles encapsulate chemotherapeutic drugs, shield them from degradation, and promote greater accumulation within tumor cites. Furthermore, liposomes can be surface-modifed with various ligands to improve their specificity and cellular uptake. Research on liposome-based targeted chemotherapy for pancreatic cancer has explored useful ligand-based strategies to enhance drug delivery to pancreatic cancer cells. In this review, liposome-based targeted strategies for pancreatic cancer are classified by ligand type, including antibodies, aptamers, carbohydrates, proteins and peptides, and integrates case studies to demonstrate how different targeting approaches translate into improved cellular uptake, therapeutic efficacy, and antitumor effects. In addition, emerging formulations such as dual-targeting liposomes are described, highlighting their potential to further strengthen treatment performance. The review summarizes the current research landscape of liposome-based targeted drug delivery systems for pancreatic cancer, providing insights into promising biomarkers and ligand-mediated targeting strategies. It further discusses broader opportunities for target exploration and liposomal design optimization, as well as future research directions aimed at overcoming existing limitations and improving therapeutic outcomes.

胰腺癌是世界上最致命的恶性肿瘤之一。这种疾病的侵袭性，加上晚期诊断和有限的治疗选择，突出了迫切需要创新的治疗方法。靶向治疗已成为一种有前途的策略，以提高治疗效果，同时尽量减少全身毒性。脂质体作为一种多用途的纳米颗粒，在药物传递系统的发展中显示出巨大的潜力。这些以脂质为基础的囊泡包裹化疗药物，保护它们免受降解，并促进肿瘤细胞内更大的积累。此外，脂质体可以用各种配体进行表面修饰，以提高其特异性和细胞摄取。基于脂质体的胰腺癌靶向化疗研究探索了有效的基于配体的策略来增强药物对胰腺癌细胞的递送。在这篇综述中，基于脂质体的胰腺癌靶向策略按配体类型分类，包括抗体、适体、碳水化合物、蛋白质和肽，并整合案例研究来证明不同的靶向方法如何转化为改善细胞摄取、治疗效果和抗肿瘤效果。此外，介绍了双靶向脂质体等新兴制剂，强调了它们进一步加强治疗性能的潜力。本文总结了目前基于脂质体的胰腺癌靶向药物递送系统的研究现状，为有前途的生物标志物和配体介导的靶向策略提供了见解。它进一步讨论了靶点探索和脂质体设计优化的更广泛机会，以及旨在克服现有局限性和改善治疗效果的未来研究方向。

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引用次数: 0

Engineering exosomes for cancer therapy - Modification technologies and subcellular targeting strategies: A review 用于癌症治疗的工程外泌体-修饰技术和亚细胞靶向策略：综述

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-31 DOI: 10.1016/j.ijpx.2025.100473

Fengbo Liu, Chengxing Xia, Hang Yu, Xiaofang Yang, Liping Ge, Chunwei Ye

Exosomes are secreted lipid bilayer vesicles of 30–150 nm in diameter. Their low immunogenicity, excellent biocompatibility, and inherent targeting capability make them a promising drug delivery vehicle for cancer therapeutics. However, the use of natural exosomes is still challenging for therapeutic applications, including limited targeting precision and drug-loading efficiency, necessitating engineered modification strategies to optimize their performance. To further enhance exosome targeting capacity, recent studies have explored precision delivery strategies targeting subcellular structures such as lysosomes, nuclei, mitochondria, and the endoplasmic reticulum, thereby improving exosome therapeutic potential. This review systematically summarizes the core advantages of exosomes as drug carriers, elaborates on their engineering modification methods, and highlights recent advances in strategies to improve exosomes targeting of subcellular structures to enhance antitumor efficacy. The review aims to provide a theoretical foundation and technical guidance for developing exosome-based precision therapies for cancer.

外泌体是直径30 ~ 150nm的脂质双分子层囊泡。它们的低免疫原性、良好的生物相容性和固有的靶向性使它们成为一种很有前途的癌症治疗药物递送载体。然而，天然外泌体的使用在治疗应用中仍然具有挑战性，包括有限的靶向精度和载药效率，需要工程修饰策略来优化其性能。为了进一步提高外泌体的靶向能力，最近的研究探索了针对亚细胞结构（如溶酶体、细胞核、线粒体和内质网）的精确递送策略，从而提高外泌体的治疗潜力。本文系统总结了外泌体作为药物载体的核心优势，阐述了其工程修饰方法，并重点介绍了近年来外泌体靶向亚细胞结构以提高抗肿瘤疗效的策略进展。本文旨在为开发基于外泌体的肿瘤精准疗法提供理论基础和技术指导。

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引用次数: 0

Improving the bioavailability of nintedanib by formulating inhalable ufasomes as a targeted therapy for non-small cell lung cancer 提高尼达尼布的生物利用度，通过制定可吸入的非小细胞肺癌的靶向治疗

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-30 DOI: 10.1016/j.ijpx.2025.100482

Salman M. Ghazwani , Sami Alhazmi , Salhah M. Ghazwani , Hussam M. Shubaily , Ahmed M. Wafi , Naifa Alenazi , Marwa Qadri , Amal Naif Alshammari , Wedad Mawkili , Jobran M. Moshi , Zenat Khired , Salama A. Salama

The safety and effectiveness of nintedanib in treating non-small cell lung cancer (NSCLC) have been evaluated in several clinical trials. However, nintedanib exhibits low oral bioavailability due to its poor solubility and first-pass metabolism. To enhance the sustainability, targeting, bioavailability, and effectiveness of nintedanib, a targeted therapy for NSCLC was developed in the form of nebulized nintedanib ufasomes (NLU). Various NLU formulations were optimized utilizing the Design Expert software. The selected NLU was then evaluated for its aerodynamics, cytotoxicity, bioavailability, and targeting capabilities. To evaluate the effectiveness and safety of the optimal NLU formulation, a dose-dependent study was conducted using a mouse model of lung cancer induced by Lewis lung carcinoma (LLC) cell lines. The selected NLU formulation increased the sustainability, bioavailability, and targeting capability of nintedanib by 49.5 %, 6.63-fold, and 8.99-fold, respectively. Additionally, it decreased the IC₅₀ value by 4.7-fold. The nebulized NLU showed better anti-tumor, anti-inflammatory, and anti-oxidative effects than oral nintedanib in terms of LDH, CEA, AFP, MDA, TNF-α, and IL-1β. The histopathological analysis confirmed these results. The safety and efficacy studies demonstrated that the nebulized NLU formulation at a dose of 100 mg/kg could serve as a viable therapy for NSCLC.

尼达尼布治疗非小细胞肺癌（NSCLC）的安全性和有效性已在多个临床试验中得到评价。然而，尼达尼布由于其溶解度和首次代谢较差，口服生物利用度较低。为了提高尼达尼布的可持续性、靶向性、生物利用度和有效性，一种以雾化尼达尼布素（NLU）形式的非小细胞肺癌靶向治疗被开发出来。利用Design Expert软件对各种NLU配方进行了优化。然后对选定的NLU进行空气动力学、细胞毒性、生物利用度和靶向能力的评估。为了评价最佳NLU配方的有效性和安全性，采用Lewis肺癌（LLC）细胞系诱导的小鼠肺癌模型进行了剂量依赖性研究。选择的NLU配方使尼达尼布的可持续性、生物利用度和靶向性分别提高了49.5%、6.63倍和8.99倍。此外，IC50值降低了4.7倍。在LDH、CEA、AFP、MDA、TNF-α、IL-1β等指标上，NLU雾化组的抗肿瘤、抗炎、抗氧化作用优于口服尼达尼布。组织病理学分析证实了这些结果。安全性和有效性研究表明，雾化NLU制剂剂量为100mg /kg，可作为一种可行的治疗NSCLC的方法。

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引用次数: 0

In vitro, ex vivo, and in vivo evaluation of ophthalmic ointments containing dexamethasone and tobramycin 含地塞米松和妥布霉素的眼软膏的体外、体外和体内评价

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-25 DOI: 10.1016/j.ijpx.2025.100476

Catheleeya Mekjaruskul , Andre O'Reilly Beringhs , Tuo Meng , Aji Alex Moothedathu Raynold , Qingguo Xu , Matthew Halquist , Bin Qin , Yan Wang , Xiuling Lu

This investigation compares in vitro release, ex vivo release and permeation, and in vivo ocular pharmacokinetics to render biologically informed evaluations of ophthalmic semi-solid drug products containing dexamethasone (hydrophobic) and tobramycin (hydrophilic). Both drugs were formulated with three petrolatum matrices (IGI® 320 A, IGI® 386, or Spectrum®) with distinct rheological character and benchmarked against the reference listed drug, Tobradex®. Temperature-sweep rheology revealed that IGI® 386 most closely reproduced the viscoelastic profile of the reference product. USP Apparatus I release testing with surfactant-free medium provided maximal discrimination for dexamethasone (Tobradex® > IGI® 320 A > IGI® 386 > Spectrum®), and rank-order release rates correlated strongly with ex vivo corneal permeation and in vivo corneal exposure. In contrast, tobramycin required a polysorbate-containing medium to resolve formulation differences in vitro, yet those differences did not persist ex vivo or in vivo, consistent with its rapid dissolution and diffusion, which attenuate matrix effects. The data demonstrate that drug solubility dictates the choice of biorelevant release conditions in petrolatum-based ophthalmic ointments: surfactant-free media capture formulation-dependent release for hydrophobic actives, whereas hydrophilic actives may yield artifactual discrimination when surfactant is present. However, formulations indistinguishable in vitro were typically similar in their in vivo ocular pharmacokinetics. By integrating tiered models, the framework enhances understanding of critical quality attributes, supports regulatory decision-making, and may help reduce reliance on animal studies, thereby expediting the development of therapeutically equivalent generic ophthalmic ointments.

本研究比较了含地塞米松（疏水）和妥布霉素（亲水）的眼科半固体药物产品的体外释放、体外释放和渗透以及体内眼药代动力学，以提供生物学信息评价。这两种药物均由三种凡夫林基质（IGI®320 A， IGI®386或Spectrum®）配制，具有不同的流变特性，并以参考上市药物Tobradex®为基准。温度扫描流变学表明，IGI®386最接近再现参考产品的粘弹性轮廓。USP Apparatus I无表面活性剂介质的释放测试为地塞米松（Tobradex®> IGI®320 A > IGI®386 > Spectrum®）提供了最大的鉴别，并且顺序释放率与离体角膜渗透和体内角膜暴露密切相关。相比之下，妥布霉素需要含有聚山梨酸酯的培养基来解决体外配方差异，但这些差异在体内或体外都不会持续存在，这与它的快速溶解和扩散一致，从而减弱了基质效应。数据表明，在以凡士林为基础的眼膏中，药物的溶解度决定了生物相关释放条件的选择：无表面活性剂的介质捕获依赖于疏水活性的配方释放，而当表面活性剂存在时，亲水活性可能产生人为区分。然而，在体外难以区分的制剂在其体内眼药代动力学中通常相似。通过整合分层模型，该框架增强了对关键质量属性的理解，支持监管决策，并可能有助于减少对动物研究的依赖，从而加快治疗等效的通用眼药膏的开发。

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引用次数: 0

Precision PEGylation of ZnO quantum dots enables selective intracellular killing of Uropathogenic E. coli via multimodal antibacterial mechanisms without inducing resistance ZnO量子点的精确聚乙二醇化能够通过多模式抗菌机制选择性地杀死尿路致病性大肠杆菌，而不会引起耐药性

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-25 DOI: 10.1016/j.ijpx.2025.100479

Jingqi Niu , Fangyuan Du , Mingxuan Zhang , Beiliang Miao , Yu Hong , Heyujia Yu , Xiaohua Liang , Mengqi Gao , Qifan Chen , Shiwei Liu , Baoshan Liu , Hongwei Xin , Zeliang Chen

The intracellular persistence and biofilm-forming capacity of uropathogenic Escherichia coli (UPEC) are major contributors to urinary tract infections (UTIs) recurrence and antibiotic failure. Here, we report a precisely engineered nanotherapeutic based on ZnO quantum dots (QDs) surface-functionalized with low-molecular-weight polyethylene glycol (PEG200), designed to enhance biocompatibility while preserving potent antibacterial activity. The optimized ZnO@PEG200 QDs exhibited excellent aqueous dispersibility, minimal cytotoxicity, and broad-spectrum efficacy against both drug-sensitive and multidrug-resistant Escherichia coli strains. Mechanistic studies revealed that the QDs exerted multimodal bactericidal effects, including Zn²⁺ ion release, membrane destabilization, intracellular reactive oxygen species (ROS) generation, genomic DNA fragmentation, and transcriptional repression of key virulence genes such as papG, FimH, and FliC. Notably, ZnO@PEG200 QDs disrupted bacterial motility and eradicated established biofilms even at sub-inhibitory concentrations. Long-term passaging assays demonstrated that sub-MIC exposure to ZnO@PEG200 QDs did not induce resistance development. In vivo, the QDs preferentially accumulated in the bladder and kidneys, significantly reduced intracellular bacterial burden, suppressed inflammatory cytokine expression, and promoted tissue repair in a murine UTIs model. Collectively, this work establishes ZnO@PEG200 QDs as a safe and effective nanoplatform for precision antimicrobial therapy, offering a resistance-free strategy for the treatment of intracellular and biofilm-associated bacterial infections.

尿路致病性大肠杆菌（UPEC）的细胞内持久性和生物膜形成能力是尿路感染（uti）复发和抗生素失效的主要原因。在这里，我们报道了一种基于低分子量聚乙二醇（PEG200）表面功能化的ZnO量子点（QDs）的精确工程纳米疗法，旨在增强生物相容性，同时保持有效的抗菌活性。优化后的ZnO@PEG200量子点具有优异的水分散性、最小的细胞毒性和广谱的抗药效果，可抑制耐药和多药大肠杆菌菌株。机制研究表明，量子点具有多模式的杀菌作用，包括Zn2+离子释放、膜不稳定、细胞内活性氧（ROS）产生、基因组DNA断裂以及关键毒力基因（如papG、FimH和flc）的转录抑制。值得注意的是，ZnO@PEG200量子点即使在亚抑制浓度下也会破坏细菌的运动并根除已建立的生物膜。长期传代实验表明，亚mic暴露于ZnO@PEG200量子点不会诱导抗性发展。在小鼠UTIs模型中，量子点优先在膀胱和肾脏积累，显著减少细胞内细菌负担，抑制炎症细胞因子表达，促进组织修复。总的来说，这项工作建立了ZnO@PEG200量子点作为精确抗菌治疗的安全有效的纳米平台，为治疗细胞内和生物膜相关的细菌感染提供了无耐药性的策略。

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引用次数: 0

Oxygen-sparing photodynamic therapy via dissolving microneedles for rheumatoid arthritis 溶微针保氧光动力治疗类风湿关节炎

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-24 DOI: 10.1016/j.ijpx.2025.100481

Lijie Zheng , Yingying Li , Xun Gu , Xinao Chang , Man Jiang , Wenjun Shao , Hanqing Zhao , Fangyuan Chen , Tao Ma , Qingqing Wang

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation, which leads to significant morbidity and disability. Although current therapies offer benefits to some patients, they often fail to fully address the intricate pathophysiology of RA, particularly the inflammatory proliferation and hypoxic microenvironment in synovial tissue. Herein, we propose an oxygen-sparing photodynamic therapy (PDT) strategy via dissolving microneedles (DMNs), in which both the photosensitizer and glycolysis inhibitor are simultaneously loaded into the DMNs for RA treatment. The strategy integrates PDT to target and suppress synovial hyperplasia and alleviate joint inflammation and bone damage. Additionally, an oxygen-sparing strategy was employed through glycolysis inhibition to improve the hypoxic microenvironment in RA, thereby potentiating PDT, reducing inflammatory microenvironmental factors, and promoting inflammatory cell death. In vitro results demonstrated that the combination treatment significantly increased reactive oxygen species (ROS) levels by 426.15 %, reduced ATP content by 34.78 %, and induced significant death in inflammatory synovial cells, decreasing cell viability to 14.69 %. In adjuvant arthritis (AA) rats, the treatment significantly reduced paw swelling by 20.99 %, alleviated splenomegaly by 39.62 %, and improved inflammation and related pathological changes in both synovial and ankle tissues. Furthermore, the treatment significantly reduced serum levels of pro-inflammatory cytokines, indicating a broad anti-inflammatory effect. This multifaceted approach not only enhances therapeutic efficacy for RA but also provides a theoretical basis for the development of innovative treatment formulations.

类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其特征是持续的关节炎症，导致严重的发病率和致残。尽管目前的治疗方法对一些患者有益，但它们往往不能完全解决RA复杂的病理生理，特别是滑膜组织中的炎症增殖和缺氧微环境。在此，我们提出了一种通过溶解微针（DMNs）的保氧光动力治疗（PDT）策略，其中光敏剂和糖酵解抑制剂同时装载到DMNs中用于治疗RA。该策略结合PDT靶向和抑制滑膜增生，减轻关节炎症和骨损伤。此外，通过抑制糖酵解，采用保氧策略改善RA的缺氧微环境，从而增强PDT，减少炎症微环境因子，促进炎症细胞死亡。体外实验结果表明，联合处理显著提高了426.15%的活性氧（ROS）水平，降低了34.78%的ATP含量，并诱导炎性滑膜细胞显著死亡，使细胞活力降低14.69%。佐剂性关节炎（AA）大鼠治疗后，足跖肿胀减轻20.99%，脾肿大减轻39.62%，滑膜和踝关节组织炎症及相关病理改变改善。此外，治疗显著降低血清促炎细胞因子水平，表明具有广泛的抗炎作用。这种多方面的方法不仅提高了RA的治疗效果，而且为创新治疗配方的开发提供了理论基础。

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引用次数: 0

Gold-incorporated hyaluronic acid nanoparticles enhance ablative radiotherapy efficacy in lung cancer 含金透明质酸纳米颗粒增强肺癌消融放疗疗效

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-23 DOI: 10.1016/j.ijpx.2025.100480

Jenny Ling-Yu Chen , Shu-Jyuan Yang , Li-Cheng Lin , Chun-Kai Pan , Ching-Yi Tsai , Yu-Sen Huang , Ke-Cheng Chen , Ming-Jium Shieh , Yu-Li Lin

We aimed to investigate the utility of Au-incorporated hyaluronic acid nanoparticles (Au/HA NPs) for improving the therapeutic efficacy of ablative radiotherapy (RT) for tumor control and microenvironment remodeling. HA-functionalized NPs exhibited uniform size, stability, and efficient SN38 encapsulation. Au incorporation increased NP diameter and reduced surface charge while remaining stable. HA and Au/HA NPs were efficiently internalized by lung cancer cells, with free HA pretreatment suppressing internalization. Moreover, Au/HA NP internalization strongly downregulated CD44 expression in lung cancer cells, confirming CD44-mediated internalization. In vitro, Au/HA NPs enhanced radiation-induced G2/M phase arrest and γH2AX foci formation with increased DNA double-strand breaks. Au/HA NPs and RT induced immunogenic cell death (ICD) in lung cancer cells, characterized by elevated reactive oxygen species, increased calreticulin surface expression, and extracellular adenosine triphosphate release. Tumor control, survival, immune infiltration, and systemic effects were investigated in vivo using A549 xenografts and Lewis lung carcinoma synchronous flank-lung tumor models. Au/HA NPs and ablative RT decreased tumor growth, reduced lung tumor burden in non-irradiated areas, and prolonged survival. This therapeutic combination led to increased infiltration of natural killer (NK), NK T, CD8⁺ T, and dendritic cells and decreased regulatory T cells, suggesting robust immunological activation. Biodistribution studies confirmed CD44-targeted tumor-specific NP accumulation. No substantial toxicity was observed. In conclusion, Au/HA NPs and ablative RT induced ICD in vivo. Au/HA NPs enhanced local and systemic immunity via radiosensitization and ICD. This NP-assisted approach may improve RT efficacy in lung cancer.

我们的目的是研究含金透明质酸纳米颗粒（Au/HA NPs）在改善消融放疗（RT）治疗肿瘤控制和微环境重塑方面的疗效。ha功能化的NPs具有均匀的尺寸，稳定性和高效的SN38封装。金的加入增加了NP直径，降低了表面电荷，同时保持稳定。HA和Au/HA NPs被肺癌细胞有效内化，游离HA预处理抑制内化。此外，Au/HA NP内化在肺癌细胞中强烈下调CD44的表达，证实了CD44介导的内化。在体外，Au/HA NPs通过增加DNA双链断裂，增强辐射诱导的G2/M相阻滞和γ - h2ax灶形成。Au/HA NPs和RT诱导肺癌细胞免疫原性死亡（ICD），其特征是活性氧含量升高，钙调蛋白表面表达增加，细胞外三磷酸腺苷释放增加。采用A549异种移植物和Lewis肺癌同步侧肺肿瘤模型在体内研究肿瘤控制、生存、免疫浸润和全身效应。Au/HA NPs和消融RT可降低肿瘤生长，减轻非辐照区肺肿瘤负荷，延长生存期。这种治疗组合导致自然杀伤细胞（NK）、NK T、CD8+ T和树突状细胞的浸润增加，调节性T细胞减少，表明强大的免疫激活。生物分布研究证实了cd44靶向肿瘤特异性NP积累。未观察到明显的毒性。综上所述，Au/HA NPs和消融RT在体内诱导ICD。Au/HA NPs通过放射致敏和ICD增强局部和全身免疫。这种np辅助入路可能提高肺癌放疗的疗效。

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引用次数: 0

Liposomal antimicrobials in the fight against bacterial and fungal pathogens: Clinical successes and development challenges 抗细菌和真菌病原体的脂质体抗菌剂：临床成功和发展挑战

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-23 DOI: 10.1016/j.ijpx.2025.100478

Hussein T. Kenaan , Ross M. Duncan , Wafa T. Al-Jamal , David S. Jones , Gavin P. Andrews , Brendan Gilmore , Vanessa Yardley , Nicola Farrington , Katharine E. Stott , David Lawrence , Joseph N. Jarvis , Thomas S. Harrison , Stephen Robinson , Isabela Ribeiro , William Hope , Yiwei Tian

Bacterial, fungal, and protozoan infections pose a rapidly escalating threat to global health, exacerbated by the rise in antimicrobial resistance. Current therapies against microbial pathogens are limited by high systemic toxicity and poor drug solubility. Liposomal formulations (spherical vesicles composed of lipid bilayers) have demonstrated remarkable clinical potential in addressing these concerns, as evidenced by the marketed products AmBisome® and Arikayce®. These products, which deliver amphotericin B via parenteral injection and amikacin via inhalation, exemplify how liposomes effectively mitigate drug-associated toxicity, enhance therapeutic efficacy, and overcome the biological barriers inherent to infection sites, including complex microbial biofilms, mucosal interfaces, or the blood–brain barrier. Complementary insights from anticancer research indicate that strategic manipulation of liposomal composition and structure can enhance their therapeutic potential. Adjustments in lipid charge, fluidity, and PEGylation, in particular, highlight their versatility and broad applicability for antimicrobial drug delivery. Liposomal antimicrobials can modulate pharmacokinetic profiles, achieve targeted release at sites of infection, and increase local drug concentrations, which are key advantages over conventional treatments. Despite these therapeutic advances, successful clinical translation and widespread adoption of liposomal antimicrobials remain highly dependent on overcoming existing technological and manufacturing challenges. This review emphasises the need for a paradigm shift within liposomal antimicrobial development, encouraging progression from initial research and development toward scalable, reproducible, and economically viable commercial manufacturing platforms. This transition is essential not only for ensuring the global accessibility and affordability of existing therapies but also for expanding the development of clinically relevant liposomal antimicrobial nanomedicines.

细菌、真菌和原生动物感染对全球健康构成了迅速升级的威胁，抗菌素耐药性的上升加剧了这一威胁。目前针对微生物病原体的治疗受到高全身毒性和药物溶解度差的限制。脂质体制剂（由脂质双层组成的球形囊泡）在解决这些问题方面显示出显著的临床潜力，上市产品AmBisome®和Arikayce®证明了这一点。这些产品通过肠外注射递送两性霉素B，通过吸入递送阿米卡星，证明了脂质体如何有效减轻药物相关毒性，提高治疗效果，并克服感染部位固有的生物屏障，包括复杂的微生物生物膜，粘膜界面或血脑屏障。来自抗癌研究的补充见解表明，对脂质体组成和结构的战略性操纵可以增强其治疗潜力。特别是脂质电荷、流动性和聚乙二醇化的调整，突出了它们在抗菌药物输送方面的多功能性和广泛适用性。脂质体抗菌剂可以调节药代动力学特征，在感染部位实现靶向释放，并增加局部药物浓度，这是传统治疗的关键优势。尽管有这些治疗进展，但脂质体抗菌剂的成功临床转化和广泛采用仍然高度依赖于克服现有的技术和制造挑战。这篇综述强调了脂质体抗菌药物开发模式转变的必要性，鼓励从最初的研究和开发向可扩展、可重复和经济上可行的商业制造平台发展。这种转变不仅对确保现有疗法的全球可及性和可负担性至关重要，而且对扩大临床相关脂质体抗菌纳米药物的开发也至关重要。

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引用次数: 0

Hydrogel-encapsulated antioxidant nanotherapeutics against age-related macular degeneration (AMD) oxidative damage 水凝胶包封抗氧化纳米治疗抗老年性黄斑变性（AMD）氧化损伤

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-22 DOI: 10.1016/j.ijpx.2025.100477

Jiemeng Xu , Taoyang Cai , Jing Li , Shangjie Ge-Zhang , Zhouzhou Jiang , Mingfang Cao

Age-related macular degeneration (AMD) is still the main cause of irreversible vision loss, and the current intravitreal injections is limited by frequent administration and short retinal residence time. This review summarizes the latest progress of hydrogel-nanocarrier hybrid systems, aiming at prolonging ophthalmic drug delivery and supporting retinal tissue. We summarized the pathogenesis of AMD, focusing on oxidative stress and degeneration of retinal pigment epithelium (RPE), and investigated inorganic and organic nano-platforms endowed with antioxidant, anti-inflammatory and anti-angiogenesis functions. The design strategy of embedding nanoparticles into injectable or stimulus-responsive hydrogels is discussed. However, challenges remain, including long-term biocompatibility, inflammatory response to degradation products and potential tissue accumulation. Finally, it is emphasized to accelerate clinical translation through comprehensive long-term in vivo safety evaluation, quantitative optimization of release kinetics, standardized evaluation scheme and development of extensible manufacturing process. It is worth noting that this review mainly emphasizes inorganic nanoparticles and extracellular vesicles, but does not discuss other mature organic nanocarriers in detail. These carriers have been widely studied and emphasized by many other reviews.

年龄相关性黄斑变性（AMD）仍然是不可逆视力丧失的主要原因，目前的玻璃体内注射由于给药频繁和视网膜停留时间短而受到限制。本文综述了水凝胶-纳米载体复合系统在延长眼科药物传递和支持视网膜组织方面的最新进展。我们总结了AMD的发病机制，重点关注氧化应激和视网膜色素上皮（RPE）的变性，并研究了具有抗氧化、抗炎和抗血管生成功能的无机和有机纳米平台。讨论了将纳米颗粒嵌入可注射或刺激反应型水凝胶的设计策略。然而，挑战仍然存在，包括长期生物相容性，降解产物的炎症反应和潜在的组织积累。最后，强调通过全面的长期体内安全性评价、定量优化释放动力学、标准化评价方案和开发可扩展的制造工艺来加速临床转化。值得注意的是，本文主要强调无机纳米粒子和细胞外囊泡，而没有详细讨论其他成熟的有机纳米载体。这些载体已被许多其他评论广泛研究和强调。

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引用次数: 0

Double action of HPMCAS as a dry binder and precipitation inhibitor in ASD tablet formulations of nifedipine prepared by hot-melt extrusion 热熔挤压法制备硝苯地平ASD片剂中HPMCAS干结合剂和沉淀抑制剂的双重作用

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-20 DOI: 10.1016/j.ijpx.2025.100475

David S. Nakhla , Saurabh M Mishra , Christian Lübbert , Luis Mejia , Kess Agatovure , Andreas Sauer

Poor tablet hardness and drug re-crystallization are two common challenges of amorphous solid dispersion (ASD) formulations prepared with hot-melt extrusion (HME). In the present study, we investigated the double action of hypromellose acetate succinate (HPMCAS) as a dry binder and precipitation inhibitor when externally added to high ASD load (65 %) tablets of nifedipine (NIF). Binary ASDs of NIF were prepared using either HPMCAS or copovidone (Kollidon® VA 64, PVP-VA64) as carrier polymers. Pre-dissolving HPMCAS (AS-HF) in the dissolution medium inhibited the drug precipitation and prolonged its supersaturation state at 12.5 wt % or 100 wt % relative to NIF content in ASDs prepared with either HPMCAS (1: 2, drug: polymer), or PVP-VA64 (1: 6, drug: polymer), respectively. In contrast, pre-dissolving hydroxypropyl cellulose (Klucel™, HPC-EXF) or PVP-VA64, did not prevent the drug re-crystallization. The external addition of AS-HF (5 % w/w) to the ASD tablets of NIF: HPMCAS (1: 2) improved the tabletability, compressibility and compactibility of the blend, resulting in tablets with good tensile strength (1.9 MPa) vs 1.5 MPa or 0.8 MPa with either HPC-EXF (5 % w/w) or PVP-VA64 (5 % w/w), respectively. The results from this study demonstrate, for the first time, the dual function of HPMCAS (AS-HF) as a dry binder and precipitation inhibitor in high ASD load tablets, independent of the carrier polymer. This can potentially reduce the pill burden and improve the drug bioavailability in ASD tablet formulations.

热熔挤压法制备的非晶固体分散体（ASD）制剂存在着片剂硬度差和药物再结晶的问题。在本研究中，我们研究了在高ASD负荷（65%）的硝苯地平（NIF）片中外用羟丙纤维素醋酸琥珀酸酯（HPMCAS）作为干燥粘合剂和沉淀抑制剂的双重作用。以HPMCAS或copovidone （Kollidon®VA64, PVP-VA64）为载体聚合物制备了NIF的二元asd。在HPMCAS（1:2，药物：聚合物）或PVP-VA64（1:6，药物：聚合物）制备的asd中，在溶解介质中预溶HPMCAS （AS-HF）抑制药物沉淀，并延长其过饱和状态，相对于NIF含量分别为12.5 wt %或100 wt %。相比之下，预溶羟丙基纤维素（Klucel™，HPC-EXF）或PVP-VA64不能阻止药物再结晶。在NIF: HPMCAS（1:2）的ASD片剂中加入AS-HF (5% w/w)，改善了共混物的压片性、压缩性和压实性，使片剂的抗拉强度（1.9 MPa）优于HPC-EXF （5% w/w）或PVP-VA64 （5% w/w）的片剂（1.5 MPa或0.8 MPa）。本研究的结果首次证明了HPMCAS （as - hf）在ASD高负荷片剂中作为干燥粘合剂和沉淀抑制剂的双重功能，而不依赖于载体聚合物。这可以潜在地减少ASD片剂制剂的药丸负担并提高药物的生物利用度。

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引用次数: 0