Drug Delivery最新文献

Long-term management of psoriasis recurrence via modulation of cutaneous microbiome: synergistic topical therapy with blue light and aptamer-functionalized curcumin formulation. 银屑病复发的长期管理通过调节皮肤微生物组：协同局部治疗蓝光和适配体功能化姜黄素制剂。

IF 8.1 2区医学

Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-01-03 DOI: 10.1080/10717544.2025.2610532

Nan Jin, Yaling Chen, Huangyu Luo, Yanhong Su, Yumin Weng, Xin Lin, Tingting Zheng, Bingbing Li, Tianhui Liu, Jianmin Chen

{"title":"Long-term management of psoriasis recurrence via modulation of cutaneous microbiome: synergistic topical therapy with blue light and aptamer-functionalized curcumin formulation.","authors":"Nan Jin, Yaling Chen, Huangyu Luo, Yanhong Su, Yumin Weng, Xin Lin, Tingting Zheng, Bingbing Li, Tianhui Liu, Jianmin Chen","doi":"10.1080/10717544.2025.2610532","DOIUrl":"10.1080/10717544.2025.2610532","url":null,"abstract":"The recurrence following the discontinuation of medication is a formidable challenge in managing psoriasis. Changes in the microbiome accompany the onset of psoriasis relapse, highlighting a potential therapeutic modality. To evaluate the superiority of the topical administration of aptamer-functionalized curcumin mesoporous silica (Apt-GA+Cur@μmS) plus blue light (BL) in restoring dysbiosis and intervening in recurrence in a murine model, a psoriasis relapse murine model with double imiquimod induction was established. With a BL-responsive shell, Apt-GA+Cur@μmS released curcumin (Cur) to assist BL to improve the preventative and therapeutic effects in the psoriasis relapse murine model, as evidenced by the psoriasis area and severity index, histology, splenic index, and dorsal IL-17A level. We also observed a negative correlation between splenic nitric oxide (NO) levels and the splenic index, indicating a possible mechanism by which Apt-GA+Cur@μmS&BL may function in the treatment of splenomegaly. Treatment with Apt-GA+Cur@μmS&BL exhibited a higher alpha diversity than the model group, with levels similar to those of healthy mice, indicating that this combination could adjust the composition of the dorsal microbiome to a healthier state. A reduction in the combined relative abundance of Staphylococcus, Streptococcus, and Corynebacterium as well as restoration of dysbiosis was also verified through 16S rDNA gene sequencing in vivo. Collectively, BL and Apt-GA+Cur@μmS cotherapy alleviates psoriasiform lesions in a double imiquimod-induced murine model by inhibiting IL-17A and increasing splenic NO. Additionally, this cotherapy restores the eubiosis of the dorsal lesions. Thus, it is a promising and innovative therapeutic modality for psoriasis inflammation alleviation and recurrence intervention.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2610532"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetically engineered M13 phage-mediated H9N2 DNA vaccine with enhanced mucosal and systemic immune responses in mice. 基因工程M13噬菌体介导的H9N2 DNA疫苗增强小鼠粘膜和全身免疫反应

IF 8 2区医学

Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-02-11 DOI: 10.1080/10717544.2026.2629037

Xiaohua Wang, Zhi Zhao, Mingze Shi, Shangen Xu, Xin Zhou, Kai Zhao

{"title":"Genetically engineered M13 phage-mediated H9N2 DNA vaccine with enhanced mucosal and systemic immune responses in mice.","authors":"Xiaohua Wang, Zhi Zhao, Mingze Shi, Shangen Xu, Xin Zhou, Kai Zhao","doi":"10.1080/10717544.2026.2629037","DOIUrl":"10.1080/10717544.2026.2629037","url":null,"abstract":"Vaccine adjuvants and delivery systems have long been used in DNA vaccines to enhance immunogenicity. In this study, we developed a DNA vaccine delivery platform by combining N-2-hydroxypropyl trimethyl ammonium chloride chitosan/carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS NPs) with a genetically engineered M13 phage containing the HA gene of H9N2 AIV (HA-M13). The composite NPs (HA-M13/N-2-HACC/CMCS) had an average particle size of 135.24 ± 4.36 nm, and the HA gene encapsulated in the composite NPs could be expressed in vitro. Additionally, the N-2-HACC/CMCS NPs exhibited high stability and effectively protected the HA gene and M13 phage from degradation while sustaining antigen release. Furthermore, the N-2-HACC/CMCS NPs promoted the maturation of DC2.4, enhanced MHC I and MHC II pathways and improved cellular, humoral, and mucosal immune responses. Mice immunized with HA-M13/N-2-HACC/CMCS via nasal and intramuscular injections presented higher anti-H9N2 AIV antibody titers than those given the commercial vaccine. Lymphocyte proliferation, as well as the levels of the cytokines IL-2, IL-4, IFN-γ, CD4+, and CD8+ T lymphocyte levels, also significantly increased. The nanovaccine provided effective protection against H9N2 AIV infection for 154 days postimmunization, surpassing the 120-day protection provided by the commercial vaccine. Consequently, the N-2-HACC/CMCS NPs loaded with M13 phages exhibit significant potential as vaccine adjuvants and mucosal immune delivery system.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2629037"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gallic acid-driven core-shell nanovehicles enable intestinal adhesion and adipose retention for enhanced oral bioavailability of cholecalciferol. 没食子酸驱动的核壳纳米载体能够促进肠道粘附和脂肪保留，从而提高胆骨化醇的口服生物利用度。

IF 8 2区医学

Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-05-10 DOI: 10.1080/10717544.2026.2669030

Guangyu Fan, Jixiang Zhao, Ru Zhang, Zhuo Li, Haifeng Wu, Yang Lu, Ying Li, Zhengqi Dong

{"title":"Gallic acid-driven core-shell nanovehicles enable intestinal adhesion and adipose retention for enhanced oral bioavailability of cholecalciferol.","authors":"Guangyu Fan, Jixiang Zhao, Ru Zhang, Zhuo Li, Haifeng Wu, Yang Lu, Ying Li, Zhengqi Dong","doi":"10.1080/10717544.2026.2669030","DOIUrl":"10.1080/10717544.2026.2669030","url":null,"abstract":"Cholecalciferol (VDC), a vital form of vitamin D, is essential for maintaining calcium-phosphorus balance, promoting bone health, and regulating the immune system; however, its therapeutic potential is limited by low oral bioavailability and poor aqueous solubility. To address these issues, a multifunctional nanoparticle (NPS) was developed: VDC was first encapsulated in β-cyclodextrin (βCD) to form a stable βCD/VDC inclusion complex, improving solubility and physicochemical stability, and then coated with gallic acid (GA) to yield the core-shell nanovehicle GA/βCD/VDC-NPS, which leverages GA's intestinal mucoadhesive and mesenteric adipose retention. GA/βCD/VDC-NPS exhibited a particle size of 234.1 ± 5.23 nm, high encapsulation efficiency (81.2 ± 0.13%), and drug-loading capacity (20.10 ± 0.50%), and showed sustained release, with a cumulative release of 86.06 ± 2.35% at 72 h. MDCK (Madin-Darby Canine Kidney cells) cell experiments showed its cellular uptake was significantly higher than βCD/VDC or free VDC, mediated by multiple endocytic mechanisms. Pharmacokinetic analysis supported markedly enhanced oral absorption: relative to free VDC, the bioavailability of GA/βCD/VDC-NPS increased 2.87-fold in plasma, 6.75-fold in the small intestine, 3.40-fold in adipose tissue, and 3.50-fold in the stomach. Tissue distribution studies verified its enhanced accumulation and prolonged retention in intestinal regions and associated adipose depots. These findings highlight polyphenols like GA as bioactive shells that enhance intestinal adhesion and regional retention, improving oral hydrophobic drugs' pharmacokinetics. In conclusion, GA/βCD/VDC-NPS is a promising nanoplatform that resolves VDC's solubility and bioavailability issues via polyphenol-mediated surface functionalization, offering great potential for oral delivery of various hydrophobic active compounds.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2669030"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Self-assembled non-steroidal anti-inflammatory drug-peptide hydrogel to effectively mitigate ocular inflammation. 自组装非甾体抗炎药肽水凝胶，有效减轻眼部炎症。

IF 8 2区医学

Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-05-26 DOI: 10.1080/10717544.2026.2677302

Yuhan Hu, Yu Li, Yuqin Wu, Yutuo Zhu, Jinrun Chen, Yinghao Ding, Zhimou Yang, Xingyi Li

{"title":"Self-assembled non-steroidal anti-inflammatory drug-peptide hydrogel to effectively mitigate ocular inflammation.","authors":"Yuhan Hu, Yu Li, Yuqin Wu, Yutuo Zhu, Jinrun Chen, Yinghao Ding, Zhimou Yang, Xingyi Li","doi":"10.1080/10717544.2026.2677302","DOIUrl":"10.1080/10717544.2026.2677302","url":null,"abstract":"Pranoprofen (Pra) eye drop has been widely used in clinical practice for the efficient mitigation of ocular inflammation, but it often suffers from poor bioavailability owing to the existence of various ocular barriers (i.e. tear barrier and corneal epithelial barrier). In this study, we rationally designed and synthesized a Pra-peptide conjugate using a D-form tripeptide (i.e. phenylalanine-phenylalanine-aspartic acid; ffd) motif, and the resulting conjugate (i.e. Pra-ffd) spontaneously self-assembled into single-component supramolecular hydrogel for efficient mitigation of ocular inflammation. The generated hydrogel was thoroughly characterized using a rheometer and transmission electron microscopy (TEM). The proposed Pra-ffd hardly caused cytotoxicity in RAW 264.7, L929, and human corneal epithelial cells (HCEC). The Pra-ffd hydrogel dose-dependently reduced the levels of proinflammatory cytokines (e.g. PGE2, TNF-α, and IL-6) and intracellular reactive oxygen species (ROS) accumulation in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage. In addition, topical instillation of the Pra-ffd hydrogel exhibited good ocular tolerance and prolonged precorneal retention (>20 min), resulting in higher bioavailability compared with the Pra solution. Using an endotoxin-induced uveitis (EIU) rabbit model, we demonstrated that topical instillation of Pra-ffd hydrogel effectively mitigated the inflammatory response in the anterior chamber and significantly reduced the entry of inflammatory cells from the circulation by preserving the integrity of the blood-aqueous humor barrier. Overall, the Pra-ffd hydrogel represents a promising ocular drug delivery platform for the treatment of inflammatory ocular disorders.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2677302"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148028355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploiting the dynamics of hyperthermia-enhanced delivery of thermosensitive liposomal doxorubicin to solid tumors. 利用热敏脂质体多柔比星对实体肿瘤的热增强递送动力学。

IF 8 2区医学

Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-05-10 DOI: 10.1080/10717544.2026.2670077

Pouya Namakshenas, Johannes Crezee, H Petra Kok

{"title":"Exploiting the dynamics of hyperthermia-enhanced delivery of thermosensitive liposomal doxorubicin to solid tumors.","authors":"Pouya Namakshenas, Johannes Crezee, H Petra Kok","doi":"10.1080/10717544.2026.2670077","DOIUrl":"10.1080/10717544.2026.2670077","url":null,"abstract":"Thermosensitive liposomal (TSL) drug delivery with intravascular release under hyperthermia is a promising approach for chemotherapy of solid tumors, where the hyperthermia schedule strongly influences delivery efficacy. This study uses mathematical modeling to evaluate these effects. A compartmental modeling approach was used to simulate TSL-encapsulated doxorubicin (DOX) delivery. The model was calibrated and validated against published in vivo data from murine tumor models. Key variables included hyperthermia timing relative to TSL-DOX administration (0-60 min), duration (15-90 min), and heating pattern (continuous vs. fractional). Tumor cells exhibiting multidrug resistance (MDR), based on uptake characteristics of non-small cell lung cancer (NSCLC) and breast cancer cells, were modeled by varying cellular efflux rates. Initiating hyperthermia at peak plasma TSL levels increased the maximum intracellular DOX concentration by up to twofold compared with a 60-min delay. Tumor models characterized by NSCLC-like uptake were less responsive to prolonged hyperthermia than MCF-7 and MDA-468 breast cancer cells, showing minimal additional intracellular accumulation beyond 60 min. Low-MDR tumor models exhibited greater hyperthermia-enhanced uptake than high-MDR models. Prolonged hyperthermia increased systemic exposure to free DOX; however, the relative enhancement in tumor exposure exceeded that in systemic plasma. Continuous hyperthermia yielded a 20% higher intracellular DOX concentration after 60 min compared with a fractional schedule (4 × 15 min with 15-min cool-down intervals). For optimal delivery, hyperthermia in the stationary phase is most effective when synchronized with peak plasma TSL-DOX levels. Hyperthermia duration may require cancer-type-specific adjustment. These findings provide a mechanistic basis to inform hyperthermia protocol design.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2670077"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual-ligand-modified cantharidin nanoparticles for the treatment of hepatocellular carcinoma via the inhibition of Ephb4. 双配体修饰斑蝥素纳米颗粒通过抑制Ephb4治疗肝细胞癌。

IF 8 2区医学

Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-06-05 DOI: 10.1080/10717544.2026.2682976

Wanting Jiang, Hao Zheng, Shengmei Wang, Rubing Xu, Xi Chen, Jing Yang, Xinhua Xia

{"title":"Dual-ligand-modified cantharidin nanoparticles for the treatment of hepatocellular carcinoma via the inhibition of Ephb4.","authors":"Wanting Jiang, Hao Zheng, Shengmei Wang, Rubing Xu, Xi Chen, Jing Yang, Xinhua Xia","doi":"10.1080/10717544.2026.2682976","DOIUrl":"10.1080/10717544.2026.2682976","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, yet conventional chemotherapy is limited by poor tumor specificity and severe toxicity. Cantharidin (CTD), a natural antitumor agent, is hindered by nephrotoxicity and hepatotoxicity. This study aimed to construct a dual-ligand-modified CTD-loaded solid lipid nanoparticle (GA-FA-CSLNs) using 18-glycyrrhetinic acid (GA) for hepatocyte targeting and folate-PEG3500-DSPE (FA) for long circulation, and to evaluate its antitumor efficacy, mechanism, and safety. GA-FA-CSLNs were prepared by emulsification-ultrasonication and optimized via Box-Behnken design. The nanoparticles were characterized. In vitro antitumor activity was assessed in Huh-7 cells using CCK-8, flow cytometry, and Western blotting. In vivo efficacy and safety were evaluated in Huh-7 tumor-bearing nude mice, and pharmacokinetics in SD rats. GA-FA-CSLNs exhibited favorable physicochemical properties. In vitro studies showed enhanced cellular uptake, the lowest IC50, and 43.2% apoptosis in Huh-7 cells. Mechanistically, GA-FA-CSLNs downregulated Eph receptor B4(EphB4) and Bcl-2, while upregulating caspase-3 and Bax. In vivo, the tumor inhibition rate reached 58.67%, superior to free CTD and sorafenib, with 100% 14-day survival and no significant abnormalities in serum biochemistry or histopathology. Pharmacokinetic analysis showed prolonged elimination half-life (2.54 h) and a 3.2-fold increase in area under the blood concentration-time curve versus unmodified CSLNs. GA-FA-CSLNs represent a promising actively targeted nanoplatform that enhances CTD antitumor efficacy against HCC via EphB4 pathway inhibition while reducing systemic toxicity, offering a potential strategy for targeted HCC therapy.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2682976"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nano spray-dried powders for efficient pulmonary delivery of proteins: an emphasis on comparisons of derived metrics determined by chapters <601> and <1604>. 纳米喷雾干粉用于有效的肺部蛋白质递送：强调由章节和确定的衍生指标的比较。

IF 8 2区医学

Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-09-15 DOI: 10.1080/10717544.2026.2732440

Hao-Ying Li, Jing Guo

{"title":"Nano spray-dried powders for efficient pulmonary delivery of proteins: an emphasis on comparisons of derived metrics determined by chapters <601> and <1604>.","authors":"Hao-Ying Li, Jing Guo","doi":"10.1080/10717544.2026.2732440","DOIUrl":"10.1080/10717544.2026.2732440","url":null,"abstract":"Pulmonary protein delivery has proven to be an effective approach for the treatment of local and systemic diseases, and particles that can be efficiently inhaled into peripheral regions should possess aerodynamic sizes of <2 µm, for which nano-spray-drying (NSD) is a powerful tool for fabrication. However, NSD powders have a high specific surface area and surface energy, which causes severe agglomeration and poor aerosolization performance. To solve these problems, cyclodextrin/leucine delivery systems were constructed, which can evidently protect alkaline phosphatases (AKP) with >94% of their biological activities retained in NSD powders and endow nanoparticle-based AKP-cyclodextrin-leucine (ACL) powders with improved aerosolization behavior. This can be evidenced by the fine particle (<4.46 µm) fraction (FPF<4.46) and FPF<1.66 (in unit percentage), of only 49.9% and 18.7% for the leucine-free ACL0, while significantly increased to 82.1% and 33.1% for ACL15, and further increased to >88% and >41% for ACL30/ACL45. The USP Chapters of traditional <601> and newly published <1604> were employed to determine derived metrics for aerodynamic particle size distribution (APSD). It was demonstrated that the authenticity of fitted values calculated in Chapter <601> was severely influenced by APSD profiles, and the fitted values can have immense differences from the actual values determined in Chapter <1604> . The differences can be minimized when the APSD is unimodal and normal across sized impactor stages. Hence, the authenticity of the fitted values can be improved. These new data deepen the understanding of APSD analyses and generate insights into the improvement of value authenticity for derived metrics, henceforward facilitating continuous improvements in quality control of inhaled products.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2732440"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Next-generation composite vesicular systems: an in-depth review of proniosomes in advanced drug delivery. 新一代复合囊泡系统：前质体在晚期给药中的深入研究。

IF 8.1 2区医学

Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-01-15 DOI: 10.1080/10717544.2026.2614585

Jagabandhu Bag, Subhankar Mukhopadhyay, Gouranga Nandi, Hein Min Tun

{"title":"Next-generation composite vesicular systems: an in-depth review of proniosomes in advanced drug delivery.","authors":"Jagabandhu Bag, Subhankar Mukhopadhyay, Gouranga Nandi, Hein Min Tun","doi":"10.1080/10717544.2026.2614585","DOIUrl":"10.1080/10717544.2026.2614585","url":null,"abstract":"Proniosomes represent an advanced composite vesicular platform that integrates non-ionic surfactants, lipids, and biodegradable carriers to significantly improve drug solubility, stability, and transmembrane delivery. These dry powdery formulations are transformed into multiscale niosomes upon contact with a hydrated medium to achieve controlled release and enhanced drug permeability. This seminal review delineates the transformative potential of proniosomal systems in treating various diseases, detailing diverse routes of administration, formulation techniques, mechanisms of action, as well as their advantages and limitations. Proniosomes address major issues such as systemic toxicity, poor solubility, and erratic absorption while maintaining green chemistry principles owing to their biodegradable constituents. By critically analyzing the potential for industrial translation, this review highlights the knowledge gap on clinical studies, scalability, and regulatory issues. The translation potential has even been further enhanced by recent developments in bioconjugation and nanotechnology, such as ligand-anchored proniosomes that enable active targeting. The topic's relevance is evident, as proniosomes complement next-generation biotechnology tools, such as mRNA delivery, while offering a sustainable alternative to liposomes. By compiling the most recent data, this review strives to catalyze innovation in novel drug delivery, making it essential for researchers and pharmaceutical developers.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2614585"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12810413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular payload release from non-internalizing antibody-drug conjugates: mechanisms and linker technologies. 非内化抗体-药物偶联物的细胞外有效载荷释放：机制和连接技术。

IF 8 2区医学

Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-03-22 DOI: 10.1080/10717544.2026.2645769

Chenxi Feng, Rui Lou, Shipeng Chen, Furong Lin, Jiaqi Ge, Yuwen Zhang, Chaolong Lin, Chenghao Huang

{"title":"Extracellular payload release from non-internalizing antibody-drug conjugates: mechanisms and linker technologies.","authors":"Chenxi Feng, Rui Lou, Shipeng Chen, Furong Lin, Jiaqi Ge, Yuwen Zhang, Chaolong Lin, Chenghao Huang","doi":"10.1080/10717544.2026.2645769","DOIUrl":"10.1080/10717544.2026.2645769","url":null,"abstract":"Antibody‒drug conjugates (ADCs) have taken on a significant role in precision oncology. These molecules, referred to as 'biological missiles', can deliver cytotoxic drugs directly to cancer cells. Traditional ADCs rely on endocytosis and intracellular release of payloads, but this approach becomes complicated due to issues like antigen loss, tumor heterogeneity, and impaired endocytosis, leading to therapeutic resistance. To address these challenges, noninternalizing ADCs have been developed, utilizing extracellular payload release methods. These structures employ advanced linker technologies to ensure stability in vivo and selective activation in the tumor microenvironment, achieving effective cytotoxic diffusion among tumor cells through the 'bystander effect'. This review discusses the evolution from early linker designs to complex methods based on tumor-specific conditions or external triggers. It also examines the categories of noninternalizing ADC linkers and the latest developments in clinical research, exploring prospects for enhancing the efficacy and safety of ADCs in oncology applications.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2645769"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13011097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ultrasound-triggered platelet vehicles loading fluorescein for targeted sonodynamic therapy of glioblastoma. 装载荧光素的超声触发血小板载体用于胶质母细胞瘤的靶向声动力治疗。

IF 8 2区医学

Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-07-29 DOI: 10.1080/10717544.2026.2708389

Yu-Xin Guo, Qing Deng, Ke Li, Quan Zhang, Jie Guo, Meng-Fei Wang, Jia-Lin Wu, Hui-Mei Lei, Yue-Ying Chen, Huan Pu, Yu-Fan Gao, Yong-Hong Xu, Xiao Chen, Qing Zhou

{"title":"Ultrasound-triggered platelet vehicles loading fluorescein for targeted sonodynamic therapy of glioblastoma.","authors":"Yu-Xin Guo, Qing Deng, Ke Li, Quan Zhang, Jie Guo, Meng-Fei Wang, Jia-Lin Wu, Hui-Mei Lei, Yue-Ying Chen, Huan Pu, Yu-Fan Gao, Yong-Hong Xu, Xiao Chen, Qing Zhou","doi":"10.1080/10717544.2026.2708389","DOIUrl":"10.1080/10717544.2026.2708389","url":null,"abstract":"Glioblastoma (GBM), the deadliest primary brain malignancy, resists treatment because of the blood‒brain barrier (BBB) and intrinsic resistance mechanisms. Fluorescein (FL), a clinically approved fluorophore, shows promise as a sonosensitizer for sonodynamic therapy (SDT), but faces challenges in tumor delivery and incomplete mechanistic understanding beyond ROS-mediated damage. We developed a bioinspired platelet-based delivery platform exploiting the natural tumor-homing properties of platelets for targeted FL delivery. Platelets were loaded with fluorescein diacetate (FDA), a lipophilic prodrug that is converted intracellularly to active FL, combined with probenecid to inhibit MRP1-mediated efflux, generating the ultrasound-responsive FL@plt. In vitro, FL demonstrated sonocytotoxicity; upon low-intensity ultrasound, FL@plt rapidly released FL into GBM cells, producing significant cytotoxicity enhanced by probenecid-mediated retention. In subcutaneous and orthotopic mouse models, intravenous FL@plt with probenecid and sequential ultrasound achieved extensive tumor FL accumulation, massive necrosis, significant growth inhibition, and prolonged survival. Mechanistically, FL-SDT induces DNA damage while promoting HIF-1α degradation via the ubiquitin‒proteasome and autophagy‒lysosome pathways, thus suppressing downstream DNA repair enzymes (SMUG1 and LIG4). This dual mechanism combines direct genotoxicity with impaired DNA repair capacity, underlying the potent anti-GBM efficacy. Our platelet-based FL delivery represents a practical, safe, translational therapy for overcoming BBB limitations by disabling HIF-1α-regulated DNA repair.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2708389"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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