Asian Journal of Pharmaceutical Sciences最新文献_第2页

Artificial polysaccharide-binding protein mediates co-assembly of nanodrug and probiotics against drug-resistant infectious enteritis 人工多糖结合蛋白介导纳米药物与益生菌共组装对抗耐药感染性肠炎

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.ajps.2025.101094

Ying Sun, Jiayue Yang, Zirun Zhao, Suke Liu, Mingchun Li, Qilin Yu

Intestinal drug-resistant pathogens, e.g., Salmonella enterica subsp. enterica serovar Typhimurium (S. Tm) and enteropathogenic Escherichia coli (E. coli), frequently cause life-threatening infectious enteritis. Probiotic-based therapy is a promising way to eliminate drug-resistant pathogens for treatment of infectious enteritis, but its colonizing and therapeutic efficacy after oral administration are limited. Here, we developed a facile therapeutic agent to treat infectious enteritis by co-assembly of the peptide nanodrug melittin-loaded MSN grafted by polysaccharide-binding protein (MMPB) with the famous probiotic bacteria Lactobacillus plantarum (Lac) and Bifidobacterium animalis subsp. lactis (Bif). The nanodrug was composed of the antimicrobial peptide melittin and mesoporous silica nanoparticles exposing the artificial polysaccharide-binding protein. Owing to presence of the artificial protein on the MMPB surface, the nanodrug strongly bound and cross-linked the probiotic cells, forming the Lac+Bif+MMPB co-assembly. During co-incubation with the kanamycin-resistant E. coli strain (Ecka), the co-assembly strongly reduced the viability of Ecka, leading to the increase in the ratio of probiotic to Ecka from 1.6 to 9.2. After oral administration of the co-assembly to the mice pre-colonized by Ecka, Lac+Bif+MMPB almost eliminated the kanamycin-resistant gene in the intestine, and led to 2–3-fold higher levels of the probiotic cells than the nanodrug MMPB or the combined probiotics Lac+Bif. More importantly, in the mice suffering from enteritis caused by drug-resistant S. Tm, the co-assembly remarkably recovered the mouse body weight, reduced intestine colonization of S. Tm cells, and decreased the levels of pro-inflammatory cytokines in both serum and colons. This study realized the synthetic biology technique-mediated abiotic/biotic co-assembly for efficient treating infectious enteritis induced by drug-resistant pathogens.

肠道耐药病原体，如肠沙门氏菌亚种。血清型鼠伤寒杆菌（S. Tm）和肠致病性大肠杆菌（E. coli）经常引起危及生命的感染性肠炎。以益生菌为基础的治疗是消除传染性肠炎耐药病原体的一种很有前景的方法，但其定植和口服给药后的治疗效果有限。本研究通过将多聚糖结合蛋白（MMPB）与著名的益生菌植物乳杆菌（Lac）和动物双歧杆菌亚种共组装，开发了一种简便的感染性肠炎治疗剂。lactis (Bif)。该纳米药物由抗菌肽蜂毒素和介孔二氧化硅纳米颗粒组成，暴露出人工多糖结合蛋白。由于人工蛋白存在于MMPB表面，纳米药物与益生菌细胞强结合交联，形成Lac+Bif+MMPB共组装体。在与耐卡那霉素大肠杆菌菌株（Ecka）共孵育期间，共组装强烈降低了Ecka的活力，导致益生菌与Ecka的比值从1.6增加到9.2。经Ecka预定植的小鼠口服该共组装体后，Lac+Bif+MMPB几乎消除了肠道中的卡那霉素耐药基因，并导致益生菌细胞水平比纳米药物MMPB或复合益生菌Lac+Bif高2 - 3倍。更重要的是，在耐药S. Tm引起肠炎的小鼠中，共组装显著恢复了小鼠体重，减少了S. Tm细胞的肠道定植，降低了血清和结肠中促炎细胞因子的水平。本研究实现了合成生物学技术介导的非生物/生物共组装，有效治疗耐药病原菌诱导的感染性肠炎。

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引用次数: 0

Magnetic continuum soft robot-driven precise delivery of prodrug nanoassemblies for gastric cancer chemo-immunotherapy 磁性连续体软机器人驱动的胃癌化学免疫治疗前药纳米组件的精确递送

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.ajps.2025.101103

Yuequan Wang , Hao Ye , Denis von Arx , Yukang Li , Yifan Wang , Alexandre Mesot , Carlos Franco , Xiang-Zhong Chen , Yuting Wang , Shenwu Zhang , Salvador Pané , Meng Niu , Bradley J. Nelson , Cong Luo

Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity. Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions, due to the challenges posed by the inaccessibility of deep-seated tumors. Herein, we report a magnetic continuum soft robot capable of non-invasive and site-specific delivery of prodrug nanoassemblies-loaded hydrogel. The nanoassemblies are co-assembled from redox-responsive docetaxel prodrug and oxaliplatin prodrug, and subsequently embedded into a hydrogel matrix. The hydrogel precursor and crosslinker are synchronously delivered using the soft robot under magnetic guidance and in situ crosslinked at the gastric cancer lesions, forming a drug depot for sustained release and long-lasting treatment. As the hydrogel gradually degrades, the nanoassemblies are internalized by tumor cells. The redox response ability enables them to be selectively activated within tumor cells to trigger the release of docetaxel and oxaliplatin, exerting a synergistic anti-tumor effect. We find that the combination effectively induces immunogenic cell death of gastric tumor, enhancing antitumor immune responses. This strategy offers an intelligent and controllable integration platform for precise drug delivery and combined chemo-immunotherapy.

局部精准给药有利于提高疗效，减少脱靶毒性。由于深部肿瘤难以进入，目前的局部递送方法主要集中在浅表或术后肿瘤病变上。在此，我们报道了一种磁性连续体软机器人，能够非侵入性和位点特异性地递送载水凝胶的前体药物纳米组装体。纳米组件由氧化还原反应的多西紫杉醇前药和奥沙利铂前药共同组装，随后嵌入水凝胶基质中。将水凝胶前体和交联剂在磁引导下使用软机器人同步递送，并在胃癌病变处原位交联，形成缓释和长效治疗的药库。随着水凝胶逐渐降解，纳米组件被肿瘤细胞内化。氧化还原反应能力使其在肿瘤细胞内被选择性激活，触发多西紫杉醇和奥沙利铂的释放，发挥协同抗肿瘤作用。我们发现联合用药可有效诱导胃肿瘤免疫原性细胞死亡，增强抗肿瘤免疫应答。该策略为精准给药和化疗-免疫联合治疗提供了智能、可控的集成平台。

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引用次数: 0

Hypoxia-responsive hybrid nanoparticles loaded with fingolimod and colistin against multidrug-resistant Klebsiella pneumoniae with mature biofilm 含芬戈莫德和粘菌素的低氧反应混合纳米颗粒对抗具有成熟生物膜的多重耐药肺炎克雷伯菌

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.ajps.2025.101107

Mengting Liu , Xinrui Liu , Tengli Zhang , Yuanqiang Wang , Hong Yao , Xiwang Liu , Zhiguo Fang , Yinglan Yu , Lei Luo

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) is characterized by high mortality and risk of nosocomial transmission, and biofilm constitutes the primary challenge in the treatment of its implant-associated and refractory pulmonary infections. Notably, the hypoxic microenvironment and the physical barrier of biofilm leading to the increased tolerance of the bacteria to antibiotics. Herein, a hypoxia-responsive hybrid nanoparticle (CHLip@FLD/COL) loaded separately with anti-biofilm candidate fingolimod (FLD) and antibiotic colistin (COL) is achieved targeting antibacterial efficacy against MDR-KP in vitro and in vivo. CHLip@FLD/COL is composed of hybridizing hypoxia-responsive lipids (HLipid) and lipid A targeting materials DSPE-mPEG-COL. HLipid is synthesized by hexadecanedioic acid esterified with nitroimidazole, while DSPE-mPEG is coupling with vector COL via amide reaction. The relative level of extracellular polymeric substances and the NIR-IIb sO₂ images of the infection site are used as indicators to establish mature biofilm models. CHLip@FLD/COL readily releases FLD and COL in hypoxic conditions, and its MIC against MDR-KP is only one-sixteenth of that when COL is used alone in vitro. The nanoparticle exhibits bacterial targeting ability and antibacterial effect in the pulmonary infection and biofilm infection mice models. Bacterial loads eliminated by 4 Log₁₀ CFU and 2 Log₁₀ CFU, respectively. The strategy provides a valuable reference for the treatment of refractory infections caused by MDR-KP.

耐多药肺炎克雷伯菌（MDR-KP）的特点是高死亡率和院内传播风险，生物膜是治疗其植入物相关和难治性肺部感染的主要挑战。值得注意的是，低氧微环境和生物膜的物理屏障导致细菌对抗生素的耐受性增加。本文在体外和体内制备了一种低氧响应型混合纳米颗粒（CHLip@FLD/COL），分别负载抗生物膜候选fingolimod （FLD）和抗生素粘菌素（COL），对MDR-KP具有靶向抗菌效果。CHLip@FLD/COL是由低氧反应脂质（h脂质）和脂质A靶向材料DSPE-mPEG-COL杂交而成。h脂由十六烷二酸与硝基咪唑酯化合成，DSPE-mPEG通过酰胺反应与载体COL偶联。以细胞外聚合物质的相对水平和感染部位的NIR-IIb sO2图像为指标，建立成熟的生物膜模型。CHLip@FLD/COL在缺氧条件下容易释放FLD和COL，其抗MDR-KP的MIC仅为COL在体外单独使用时的十六分之一。该纳米颗粒在肺部感染和生物膜感染小鼠模型中表现出细菌靶向性和抗菌作用。分别用4 Log10 CFU和2 Log10 CFU去除细菌负荷。该策略为耐多药kp引起的难治性感染的治疗提供了有价值的参考。

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引用次数: 0

Advanced strategies of covalent organic framework nanomedicines in targeting and overcoming biological barriers 共价有机框架纳米药物靶向和克服生物屏障的新策略

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.ajps.2025.101066

Lei Zhong , Jinpeng Liu , Yingming Xiao , Zhenyu Song , Li Chen , Ge Li , Yi Wu

Covalent organic frameworks (COFs) are crystalline and porous materials formed from periodically organized organic molecules bonded covalently to create highly stable architectures. Their mechanical properties can be precisely adjusted through structural modifications, making COFs exceptionally suitable for applications in cancer treatment and drug delivery. This review summarizes strategies for controlling the mechanical properties of COFs, including adjustments in structural dimensions, pore sizes and host-guest interactions. The remarkable advancements in drug delivery, cancer therapy, photodynamic therapy and photothermal therapy achieved through COFs with tunable mechanical properties are then discussed. By providing deeper insights into the biomedical applications of COF systems, this review aims to foster interdisciplinary research combining nanomedicine and COF materials. Additionally, the review explores recent studies and discoveries on COFs' potential as innovative drug carriers capable of biological overcoming barriers such as the blood-brain barrier, nasal mucosa, cutaneous layers and oral mucosa. Greater insight into both the limitations and potential of COFs could pave the way for developing more effective and targeted strategies within this challenging field.

共价有机框架（COFs）是由周期性组织的有机分子共价结合形成的晶体和多孔材料，以创造高度稳定的结构。它们的机械性能可以通过结构修改来精确调节，这使得COFs特别适合用于癌症治疗和药物输送。本文综述了控制COFs力学性能的策略，包括结构尺寸、孔隙大小和主客体相互作用的调整。然后讨论了通过具有可调机械性能的COFs在药物输送，癌症治疗，光动力治疗和光热治疗方面取得的显着进步。本文旨在通过对纳米医学与纳米复合材料在生物医学领域的应用提供更深入的见解，促进纳米医学与纳米复合材料的跨学科研究。此外，本文还探讨了COFs作为创新药物载体的潜力的最新研究和发现，这些药物载体能够生物克服血脑屏障、鼻黏膜、皮肤层和口腔粘膜等屏障。更深入地了解COFs的局限性和潜力，可以为在这一具有挑战性的领域制定更有效和更有针对性的战略铺平道路。

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引用次数: 0

A self-assembled nano-spray formulation for synergistic therapy of anti-inflammation and skin repair 一种自组装纳米喷雾制剂，用于抗炎和皮肤修复的协同治疗

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.ajps.2025.101067

Qi Pan , Shiwei Zhang , Xiaojie Yan , Jiajing Guo , Bowen Li , Yuan Ping

Inflammatory skin disorders (ISDs), characterized by severe inflammation and impaired skin barrier functions, often requires persistent treatment due to chronic and relapsing natures. To address these issues, we developed a small-molecular self-assembled nanodrug (ECN) that is composed of natural epigallocatechin-3-gallate (EGCG) self-assembled with tripeptide collagen (CTP). By formulating a transdermal enhancer (cationic dendrimer) with ECN, the resulted dendrimers/ECN nanocomplex (DECN) can effectively penetrate into the skin layer, resulting in effective anti-inflammatory response and repair of skin-barrier functions. In animal models of ISDs, including atopic dermatitis (AD) and psoriasis, DECN showed remarkable skin penetration, with high level of drug deposition in the epidermal-dermal layer. By using a commercially available spray pump, DECN nanoparticles can be further translated into a spray formulation, which contributes to alleviating visible symptoms, skin lesions, and inflammatory progression of psoriasis and AD. This all-in-one spray nano-formulation offers an effective, safe, and convenient way for ISDs treatment.

炎症性皮肤病（ISDs）以严重炎症和皮肤屏障功能受损为特征，由于其慢性和复发性，通常需要持续治疗。为了解决这些问题，我们开发了一种小分子自组装纳米药物（ECN），该药物由天然表没食子儿茶素-3-没食子酸酯（EGCG）与三肽胶原（CTP）自组装而成。通过与ECN组成透皮促进剂（阳离子树状大分子），所得到的树状大分子/ECN纳米复合物（DECN）可以有效地渗透到皮肤层，从而产生有效的抗炎反应和修复皮肤屏障功能。在包括特应性皮炎（AD）和牛皮癣在内的ISDs动物模型中，DECN表现出明显的皮肤渗透，在表皮-真皮层有高水平的药物沉积。通过使用市上可用的喷雾泵，DECN纳米颗粒可以进一步转化为喷雾配方，有助于减轻牛皮癣和AD的可见症状、皮肤损伤和炎症进展。这种一体化的喷雾纳米配方为ISDs治疗提供了一种有效、安全、方便的方法。

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引用次数: 0

An erythrocyte membrane-fused plant-derived nanoparticles as a gene therapy vehicle for the treatment of CI/R injury 红细胞膜融合植物源性纳米颗粒作为基因治疗载体治疗CI/R损伤

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.ajps.2025.101089

Shiyi Li , Anni Wang , Ru Zhang , Miaomiao Zhang , Pengcheng Guo , Bixue Chen , Yangke Yuan , He Wang , Jianxin Wang

Ischemic stroke is currently the second leading cause of death worldwide, and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability. MicroRNAs have been proven to hold therapeutic potential, unfortunately, they have a low stability that hinders their clinical usage. Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles, namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion (CI/R) damage. In this study, we employed microRNA-124 as a model therapeutic gene, utilizing its engineered variant Agomir-124 (Ago124) to optimize loading efficiency. The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments. Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h, and the loading efficiency of Ago124 reached 40 %. In an in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model, Ago124@R-PDN enhanced IL-10 production in microglia by 67 % (vs 11.7 % with free Ago124), and promoted Tuj1⁺ neuronal differentiation by 2.23-fold compared with vehicle. Also, Ago124@R-PDN brought gene cargo into the brain, alleviated infarct volume, and improved functional behaviors in model mice. At last, we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein. In conclusion, our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.

缺血性脑卒中是目前全球第二大死亡原因，内源性神经发生不足是脑卒中后致残的最大原因。microrna已被证明具有治疗潜力，但不幸的是，它们的稳定性较低，阻碍了它们的临床应用。我们早期的研究表明，三七衍生的外泌体样纳米颗粒，即pdn具有绕过血脑屏障和减少脑缺血/再灌注（CI/R）损伤的潜力。在本研究中，我们将microRNA-124作为模型治疗基因，利用其工程变体Agomir-124 （Ago124）优化装载效率。在几组实验中进一步评估Ago124@R-PDN的治疗效果。药代动力学研究表明，红细胞膜将pdn的半衰期从7 min延长至11.3 h， Ago124的负载效率达到40% %。在体外氧糖剥夺/再灌注（OGD/R）模型中，Ago124@R-PDN使小胶质细胞中IL-10的产生增加了67 %（与游离Ago124相比为11.7 %），并使Tuj1+神经元的分化比对照提高了2.23倍。此外，Ago124@R-PDN将基因货物带入大脑，减轻了梗死体积，并改善了模型小鼠的功能行为。最后，我们证明了PDN的表面糖基通过被钠-葡萄糖连接转运蛋白-1识别来促进其进入脑的能力。总之，我们的红细胞融合pdn提供了一种很有前途的递送生物大分子治疗脑疾病的策略。

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引用次数: 0

Celastrol-loaded metal-phenolic nanozymes integrated microneedles with ROS scavenging and anti-inflammatory activities for psoriasis treatment 含有celastrol的金属-酚纳米酶集成微针，具有ROS清除和抗炎活性，用于治疗牛皮癣

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.ajps.2025.101062

Li Qin , Haozheng Jiao , Yu Wang , Lvyao Yang , Xianbao Shi , Peng Zhang

Psoriasis is a chronic inflammatory skin disease, which seriously affects the physical and mental health of patients. The progression of psoriasis is influenced by the excessive production of reactive oxygen species (ROS) and inflammatory responses. In this paper, novel celastrol (Ce)-loaded metal-phenolic nanozymes (tannic acid-Fe³⁺) (TA-Fe) integrated microneedles (Ce@TA-Fe/MNs) were constructed to achieve the combined oxidative stress alleviation and anti-inflammatory therapy of psoriasis. Molecular dynamics simulations and structural characterization confirmed the successful fabrication of nanozymes. The Ce@TA-Fe/MNs system, characterized by its rapid dissolution kinetics and superior mechanical strength, enabled minimally invasive skin penetration for efficient nanozymes delivery. Nanozymes possessed superoxide dismutase and catalase mimetic enzyme activities, effectively eliminating excessive ROS in psoriatic skin lesions. Additionally, the release of Ce from Ce@TA-Fe provided strong antioxidant and anti-inflammatory effects. Based on these characteristics, Ce@TA-Fe/MNs could effectively alleviate the symptoms in psoriasis mice models. These findings demonstrated that the integration of Ce-equipped nanozymes within MNs holds great promise as a therapeutic strategy for the clinical management of psoriasis.

牛皮癣是一种慢性炎症性皮肤病，严重影响患者的身心健康。银屑病的进展受活性氧（ROS）过量产生和炎症反应的影响。为了实现银屑病的氧化应激缓解和抗炎联合治疗，本文构建了一种新型的负载celastrol （Ce）的金属-酚纳米酶（鞣酸- fe3 +）（TA-Fe）集成微针（Ce@TA-Fe/MNs）。分子动力学模拟和结构表征证实了纳米酶的成功制备。Ce@TA-Fe/MNs系统以其快速溶解动力学和优异的机械强度为特点，实现了微创皮肤渗透，高效递送纳米酶。纳米酶具有超氧化物歧化酶和过氧化氢酶模拟酶活性，可有效消除银屑病皮损中过量的活性氧。此外，从Ce@TA-Fe中释放的Ce具有很强的抗氧化和抗炎作用。基于这些特点，Ce@TA-Fe/MNs可有效缓解银屑病小鼠模型的症状。这些发现表明，在MNs中整合ce装备的纳米酶作为牛皮癣临床治疗的治疗策略具有很大的前景。

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引用次数: 0

Extracellular vesicles in cancer immunotherapy: Therapeutic, challenges and clinical progress 肿瘤免疫治疗中的细胞外囊泡：治疗、挑战和临床进展

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.ajps.2025.101065

Hamed Manoochehri , Anita S. La'ah , Ali Babaeizad , Mohsen Sheykhhasan , Mohadeseh Rostamipoor , Mahdiyeh Abbaspoor , Fariba Nikravesh , Samira Mozaffari Khosravi , Hanie Mahaki , Hamid Tanzadehpanah , Piao Yang

Cancer is a major global concern due to its high mortality rate. Tumor immunotherapy has revolutionized cancer treatment. However, low response rates and immune-related complications remain challenges. Extracellular vesicles (EVs), including exosomes, have emerged as promising therapeutic tools for various pathological conditions, especially cancer. Evidence indicates that changes in the quantity and composition of EVs can influence the immunosuppressive tumor microenvironment, potentially affecting the effectiveness of immunotherapy. Exploiting EVs for immune sensitization has generated significant clinical interest. This review provides an in-depth understanding of the origin of EVs, their therapeutic applications (such as drug delivery nanoplatforms and cancer immunotherapies, including vaccines), diagnostic potential as tumor biomarkers, ongoing EV-based clinical trials, and the challenges encountered in EV-based cancer immunotherapy.

癌症因其高死亡率而成为全球关注的主要问题。肿瘤免疫疗法使癌症治疗发生了革命性的变化。然而，低应答率和免疫相关并发症仍然是挑战。细胞外囊泡（EVs），包括外泌体，已经成为治疗各种病理疾病，特别是癌症的有前途的治疗工具。有证据表明，ev的数量和组成的变化可以影响免疫抑制性肿瘤微环境，可能影响免疫治疗的有效性。利用ev进行免疫致敏已经引起了重大的临床兴趣。本文综述了ev的起源，其治疗应用（如药物递送纳米平台和癌症免疫疗法，包括疫苗），作为肿瘤生物标志物的诊断潜力，正在进行的ev临床试验，以及在ev癌症免疫治疗中遇到的挑战。

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引用次数: 0

Bioengineered milk-derived extracellular vesicles implementing high drug loading and membrane integrity for efficient oral drug delivery 生物工程牛奶衍生的细胞外囊泡实现高药物负载和膜完整性，用于有效的口服药物递送

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.ajps.2025.101093

Mingjie Ni, Liyun Xing, Yating Wang, Xi Liu, Lie Zhang, Yuting Li, Lian Li, Yuan Huang

Milk-derived extracellular vesicles (EVs) are promising for oral drug delivery, yet different loading methods exhibit distinct impacts on drug encapsulation and membrane integrity. This study demonstrated that sonication method achieved high drug encapsulation in commercial milk-derived EVs (S-CM EVs), but impaired EV structure, compromising transcytosis. Incubation method (I-CM EVs) preserved EVs delivery ability, but had low drug loading. Further proteomic and transmembrane studies showed that sonication greatly damaged membrane proteins involved in trans-epithelial transportation, especially endoplasmic reticulum-Golgi pathway. To overcome this dilemma, we generated a hybrid CM EVs (HCM EVs) by fusing I-CM EVs and S-CM EVs. HCM EVs demonstrated comparable drug encapsulation to S-CM EVs (56.14 %), significantly higher than I-CM EVs (11.92 %). Importantly, HCM EVs could maintain efficient drug delivery capability by restoring membrane fluidity, repairing damaged proteins, and enhancing enzyme resistance of S-CM EVs. HCM EVs exhibited excellent absorption characteristics with 1.85-fold higher of area under the curve and 2.50-fold higher of max plasma concentration than those of S-CM EVs. On type Ⅰ diabetic mice, orally delivery of insulin loaded HCM EVs and I-CM EVs showed improved hypoglycemic effects with pharmacological availabilities of 5.15 % and 5.31 %, which was 1.7-fold higher than that of S-CM EVs (3.00 %). This HCM EVs platform not only achieved high drug loading and maintained functionality for effective oral delivery but also highlighted the significant translational potential for improved clinical outcomes.

乳源性细胞外囊泡（ev）是一种很有前途的口服药物递送工具，但不同的装载方式对药物包封和膜完整性的影响不同。该研究表明，超声方法在商业乳源性EV （S-CM EV）中实现了高药物包封，但损害了EV结构，影响了胞吞作用。培养法（I-CM ev）保留了ev的递送能力，但载药量较低。进一步的蛋白质组学和跨膜研究表明，超声极大地破坏了参与跨上皮运输的膜蛋白，特别是内质网-高尔基通路。为了克服这一困境，我们将I-CM电动汽车和S-CM电动汽车融合在一起，产生了混合CM电动汽车（HCM电动汽车）。HCM ev的药物包封率与S-CM ev相当（56.14%），显著高于I-CM ev（11.92%）。重要的是，HCM ev可以通过恢复膜流动性、修复受损蛋白质和增强S-CM ev的酶抗性来保持有效的药物递送能力。HCM ev的曲线下面积和最大血浆浓度分别是S-CM ev的1.85倍和2.50倍，具有良好的吸收特性。在Ⅰ型糖尿病小鼠中，口服胰岛素负载的HCM ev和I-CM ev具有改善的降糖作用，其药理效价分别为5.15%和5.31%，比S-CM ev（3.00 %）高1.7倍。该HCM ev平台不仅实现了高药物负荷和维持有效口服给药的功能，而且突出了改善临床结果的显著转化潜力。

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引用次数: 0

Macrophage-centered therapy strategies: A promising weapon in cancer immunotherapy 巨噬细胞为中心的治疗策略：癌症免疫治疗的一个有前途的武器

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.ajps.2025.101063

Simiao Wang , Jiayi Liu , Yaxin Cui , Man Sun , Wei Wang , Jiayi Chen , Jingkai Gu , Zhaogang Yang

Macrophages are critical phagocytes in the immune system, and tumor-infiltrating macrophages can substantially influence the efficacy and prognosis of immunotherapy. Therefore, macrophages may serve as therapeutic targets for modulating the tumor immune microenvironment. Macrophage-based drug delivery systems have been extensively evaluated owing to their excellent biocompatibility, long half-life, and inherent ability to migrate and accumulate at sites of inflammation, such as tumors. Live macrophages and their membrane coatings contain abundant receptor proteins that facilitate payload transport across physiological barriers. In this review, we discuss strategies that utilize macrophages as targets and delivery carriers for cancer immunotherapy. Here, we summarize the different macrophage phenotypes, tumor-associated macrophage-targeting strategies, and biomimetic delivery carriers derived from macrophages used in immunotherapy. Overall, macrophage-centered strategies for cancer therapy hold considerable promise for clinical applications.

巨噬细胞是免疫系统中至关重要的吞噬细胞，肿瘤浸润性巨噬细胞对免疫治疗的疗效和预后有重要影响。因此，巨噬细胞可能作为调节肿瘤免疫微环境的治疗靶点。巨噬细胞为基础的药物传递系统由于其优异的生物相容性、较长的半衰期以及在炎症部位（如肿瘤）迁移和积累的固有能力而被广泛评估。活的巨噬细胞及其膜涂层含有丰富的受体蛋白，促进有效载荷跨越生理屏障的运输。在这篇综述中，我们讨论了利用巨噬细胞作为肿瘤免疫治疗的靶点和递送载体的策略。在这里，我们总结了不同的巨噬细胞表型，肿瘤相关的巨噬细胞靶向策略，以及免疫治疗中巨噬细胞衍生的仿生递送载体。总的来说，以巨噬细胞为中心的癌症治疗策略具有相当大的临床应用前景。

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