Jiazhen Zhu , Haonan Zhang , Jinmin Lin , Yuqi Wang , Zheng Shi , Fanzhu Li , Wendong Yao
{"title":"Development and evaluation of Strychni semen total alkaloid-loaded transfersomes for targeted articular delivery in osteoarthritis","authors":"Jiazhen Zhu , Haonan Zhang , Jinmin Lin , Yuqi Wang , Zheng Shi , Fanzhu Li , Wendong Yao","doi":"10.1016/j.jddst.2026.108046","DOIUrl":"10.1016/j.jddst.2026.108046","url":null,"abstract":"<div><div>Strychni semen contains bioactive total alkaloids effective against osteoarthritis (OA). However, their utility is limited by rapid clearance and potential toxicity to the central nervous system (CNS) and kidneys. To overcome these limitations, we developed a novel transdermal delivery system utilizing transfersomes loaded with majorizing Strychni semen total alkaloids (M-SSA-TFSs). Compared with conventional liposomes, M-SSA-TFSs demonstrated excellent stability, high drug encapsulation efficiency, and significantly enhanced skin permeation. Pharmacodynamic and pharmacokinetic evaluations using double-sited microdialysis confirmed that M-SSA-TFSs significantly inhibited pro-inflammatory cytokines, protected cartilage structure, and maintained sustained therapeutic drug levels in both the joint cavity and systemic circulation. Furthermore, the delivery system demonstrated favorable biocompatibility with healthy chondrocytes while exhibiting therapeutic efficacy against OA. Consequently, this study highlights M-SSA-TFSs as a superior transdermal approach that improves the dermal absorption and therapeutic index of Strychni semen, providing a valuable strategy for decelerating OA progression.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108046"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Majid Ghaedi , Jaleh Varshosaz , Mohammad Rabbani , Amir Mohammadsharifi Renani
{"title":"Transdermal delivery of zaleplon through dissolving-swellable microneedles: An in vitro/ in vivo study in rats with insomnia induced by para-chlorophenylalanine","authors":"Majid Ghaedi , Jaleh Varshosaz , Mohammad Rabbani , Amir Mohammadsharifi Renani","doi":"10.1016/j.jddst.2026.108058","DOIUrl":"10.1016/j.jddst.2026.108058","url":null,"abstract":"<div><div>Microneedles represent a type of formulation utilized for the transference of materials through the skin. The rate at which substances are transferred into the body can be controlled in comparison to oral and parenteral methods, thereby potentially reducing side effects. The aim of this study was to develop dissolving microneedle patches (MNPs) from zaleplon, a non-benzodiazepine sleep inducer. Zaleplon exhibits low solubility in water and possesses a 30 % oral bioavailability due to considerable first-pass metabolism; thus, enhancing its solubility is crucial for more effective and rapid delivery via microneedles. As a result, a solvent exchange method utilizing a 5:1 ratio of polyvinyl alcohol (PVA) to drug was employed to formulate a dispersion of zaleplon within a hydrophilic polymer. This was subsequently followed by freeze-drying to obtain a solid dispersion of the drug. After characterizing the solid dispersions of zaleplon through measurements of saturated solubility, X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), the material was utilized to fabricate dissolving microneedles using a micro-molding approach. Various ratios of polyvinyl pyrrolidone (PVP), PVA, and hydroxypropyl methylcellulose (HPMC) were employed as the base for the microneedles, and the resulting microneedles were evaluated for their zaleplon content, release from MNPs, mechanical properties, skin penetration capability, hydrophilicity, structural stability, swell-ability and <em>in vitro</em> deformation. Then the effects of oral zaleplon and MNPs were assessed regarding sleep duration and onset in rats with para-chlorophenylalanine-induced insomnia. The solid dispersion of zaleplon enhanced its water solubility by 6 times (242.03 ± 16.99 μg/mL <em>vs</em>. 40 μg/mL). The optimal formulation comprised 40 wt% PVA, 40 wt% PVP, and 20 wt% HPMC, which facilitated easy penetration into the skin and released over 70 % of zaleplon within 60 min. <em>In vivo</em> results demonstrated that zaleplon microneedles had a faster onset of action (approximately 7.5 min quicker) and extended the duration of sleep more than twice as long as the oral group (100 min compared to 40 min). It can be concluded that zaleplon MNP might be more effective than the oral administration method in managing insomnia.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108058"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salma N. Hassan , Mohamed A. Abdelkhalek , Ahmed Y. Gamal , Maged A. El-Kemary , Sara A. Abdel Gaber
{"title":"Simvastatin loaded marine collagen-silk fibroin electrospun nanofiber as a bioactive guided tissue membrane for regenerative and anti-inflammatory therapy","authors":"Salma N. Hassan , Mohamed A. Abdelkhalek , Ahmed Y. Gamal , Maged A. El-Kemary , Sara A. Abdel Gaber","doi":"10.1016/j.jddst.2026.108062","DOIUrl":"10.1016/j.jddst.2026.108062","url":null,"abstract":"<div><div>Collagen membranes used for Guided Tissue Regeneration (GTR) and wound healing provide adequate biocompatibility, but lack sufficient porosity and can't provide controlled drug delivery needed to support predictable healing. This study aims to address these limitations by developing an electrospun nanofibrous membrane composed of silk fibroin (SF) blended with marine collagen (MCOL) and loaded with Simvastatin (Simva) generating for the first time this bioactive dressing. The membrane was characterized for its morphology, mechanical properties, degradation behavior, and Simva release profile was monitored. Its biological performance was evaluated at the <em>in vitro</em> level and at the <em>in vivo</em> level using full-thickness wound model. The Simva@SF/MCOL membrane showed uniform randomly oriented nanofibers with a mean diameter between 250 and 300 nm and a surface pore diameter of 0.6–1.6 μm. More than 80 % weight loss was achieved over 6 weeks as concluded by assays using artificial saliva. The tensile strength of our Simva/SF/MCOL membrane was 1.7 MPa. Simva release followed Korsmeyer-Peppas model. The membrane was inert to fibroblasts and decreased iNOS and NO level of cells in the scratch wound assay. Animal studies proved the outperformance of Simva @SF/MCOL over commercial collagen membrane and Simva free nanofibers. The wound closure was significantly fostered by the inclusion of Simva as indicated by a closure percentage exceed 90 % within 14 days compared to 80 % in the case of commercial collagen and Simva free nanofibers. That was accompanied with collagen deposition, significant suppression of the inflammatory markers IL-1β and TNF-α. These findings suggest that our first time to be fabricated Simva@SF/MCOL nanofiber offers a bioactive nanotechnology-based membrane outperforming the commercially available membranes used in GTR applications and thus can improve the therapeutic outcome.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108062"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sustained-release sodium alginate-based metformin/bentonite nanocomposite hydrogel for enhanced wound healing","authors":"Zahra Rezanejad Gatabi , Mehri Mirhoseini , Mozhgan Abasi , Mohammad Shokati Sayyad , Pedram Ebrahimnejad","doi":"10.1016/j.jddst.2026.108035","DOIUrl":"10.1016/j.jddst.2026.108035","url":null,"abstract":"<div><div>Hydrogels are promising wound dressings, yet traditional hydrogels often lack optimal mechanical strength and antimicrobial activity. We developed a novel sodium alginate-based metformin-loaded bentonite (Met-Ben) nanocomposite hydrogel to enhance wound healing. Metformin was encapsulated within bentonite nanoparticles via ion-exchange, achieving an entrapment efficiency of 75.6 % and a drug-loading value of 27.7 %. The nanoparticles had an average size of 364.5 nm and a zeta potential of −8.6 mV. The hydrogel exhibited an increased swelling ratio over 4 h and showed approximately 65 % degradation over 14 days. Sustained metformin release followed Korsmeyer-Peppas kinetics (n = 0.3541, indicating Fickian diffusion). ATR-FTIR and DSC confirmed the chemical integrity and amorphous state of encapsulated metformin. In vitro cytotoxicity assays confirmed its biocompatibility. In vivo, the Met-Ben hydrogel significantly accelerated wound closure (85 % at day 14), increased collagen deposition (p < 0.05, histological scoring), and enhanced fibroblast maturation, re-epithelialization, and neovascularization compared with the control. Gene expression analysis showed downregulation of TNF-α and IL-1β and upregulation of TGF-β (p < 0.01), supporting modulation of inflammation and promotion of tissue regeneration. This study introduces the first sodium alginate–bentonite–metformin nanocomposite hydrogel, offering a dual-action bioactive and structural platform for full-thickness wound healing.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108035"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdeslam Assafi , Lamia Hejji , Mohamed Amine Zarouki , Youssef Aoulad El Hadj Ali , Luis Pérez-Villarejo , Béla Fiser , Badredine Souhail , Abdelmonaim Azzouz
{"title":"Development and evaluation of a graphene oxide–silver nanoparticle– bisdemethoxycurcumin nanocomposite for advanced wound management","authors":"Abdeslam Assafi , Lamia Hejji , Mohamed Amine Zarouki , Youssef Aoulad El Hadj Ali , Luis Pérez-Villarejo , Béla Fiser , Badredine Souhail , Abdelmonaim Azzouz","doi":"10.1016/j.jddst.2026.108001","DOIUrl":"10.1016/j.jddst.2026.108001","url":null,"abstract":"<div><div>Wound management remains a significant challenge in clinical practice, requiring effective and innovative solutions. To address this need, this study explores the potential of a novel nanocomposite composed of graphene oxide (GO), silver nanoparticles (AgNPs), and bisdemethoxycurcumin (Cur), denoted as GO@AgNPs@Cur nanocomposite. The successful synthesis of this nanocomposite was confirmed through comprehensive characterization techniques, including Fourier-transform infrared spectroscopy (FTIR), Ultraviolet–Visible Spectroscopy (UV–vis), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and ζ-potential analysis. The therapeutic potential of GO@AgNPs@Cur nanocomposite was evaluated through both <em>in-vivo</em> and <em>in-vitro</em> experiments. In the <em>in-vivo</em> study, full-thickness wounds were carefully induced on the dorsum of mice and treated with GO@AgNPs@Cur nanocomposite. Notably, the composite achieved exceptional wound contraction (97.74 ± 1.10 %) by day 9, significantly outperforming the untreated (53.72 ± 2.11 %) and povidone iodine-treated (58.00 ± 2.64 %) groups. <em>In vitro</em> experiments demonstrated strong antibacterial activity against both Gram-positive (<em>S. aureus</em>) and Gram-negative (<em>E. coli</em>) strains, with an MIC and MBC of 117 μg/mL. Additionally, the nanocomposite exhibited excellent antioxidant properties, with a maximum scavenging activity of 85.57 ± 3.96 % and an IC<sub>50</sub> of 94.28 μg/mL, as determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. These findings underscore the potential of the GO@AgNPs@Cur nanocomposite as an effective wound healing material with strong antibacterial and antioxidant properties, offering significant promise for advanced wound management.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108001"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Zhang , Jing Wen , Tie Li , Junshuang Xu , Jinbiao Ma , Min Hong , Wei Li
{"title":"Preclinical development and evaluation of Uricase mRNA-loaded lipid nanoparticles for the treatment of hyperuricemia","authors":"Jing Zhang , Jing Wen , Tie Li , Junshuang Xu , Jinbiao Ma , Min Hong , Wei Li","doi":"10.1016/j.jddst.2026.108029","DOIUrl":"10.1016/j.jddst.2026.108029","url":null,"abstract":"<div><div>Hyperuricemia (HU), a common metabolic disorder, is characterized by elevated serum uric acid (sUA) levels. Uricase, an enzyme that degrades uric acid(UA) into allantoin, is absent in humans due to a nonsense mutation. Messenger RNA (mRNA)-based protein replacement therapy, known for its efficiency and transient expression, has garnered significant research attention. This study focuses on developing a mRNA therapy for HU using human ancestral uricase ANC19, delivered via lipid nanoparticles (LNPs). We prepared ANC19-LNPs, characterized their physicochemical properties, and evaluated their expression and function in Huh7 cells. Results indicate successful preparation and characterization of ANC19-mRNA, which localizes to peroxisomes and demonstrates UA degradation capability in vitro. Biodistribution was validated in Balb/c mice. Concurrently, a HU mouse model was successfully established using siRNA-mediated knockdown of Uricase-mRNA. In HU mouse models, ANC19-LNPs achieved a 75.63 % UA degradation rate. To validate these promising findings in a more clinically relevant species, the therapy was evaluated in cynomolgus monkeys, where it also showed a therapeutic effect, the area under the curve (AUC) of the concentration-time curve for ANC19-LNPs was 32.647 h∗μg/mL compared to 67.074 h∗μg/mL for the negative control. Biochemical blood tests in cynomolgus monkeys confirmed the safety of ANC19-LNPs. In conclusion, we have successfully developed an effective mRNA-based protein replacement therapy for UA degradation, showing promising efficacy and safety in both in vitro and in vivo studies.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108029"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiqian Gu , Songou Zhang , Guoqing Li , Xudong Hu , Nanjian Xu , Yang Wang , Jian Ruan , Weihu Ma , Hong Chen
{"title":"Genistein-loaded mesenchymal stem cells (MSCs)-derived exosomes: A novel drug carrier for targeted osteosarcoma treatment via PPARγ pathway","authors":"Zhiqian Gu , Songou Zhang , Guoqing Li , Xudong Hu , Nanjian Xu , Yang Wang , Jian Ruan , Weihu Ma , Hong Chen","doi":"10.1016/j.jddst.2025.107862","DOIUrl":"10.1016/j.jddst.2025.107862","url":null,"abstract":"<div><div>Osteosarcoma, a very aggressive bone cancer, poses considerable therapeutic hurdles because it is resistant to conventional therapies. The objective of this work was to develop a novel genistein-based therapeutic formulation by encapsulating the compound into exosomes derived from mesenchymal stem cells (MSCs) and to evaluate its <em>in vitro</em> efficacy against osteosarcoma. The physicochemical characteristics of the genistein-loaded exosomes (Exo-Gen) were analysed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) Osteosarcoma cell line MG63 were treated with Exo-Gen, and their effects on cell viability, cellular uptake and migration were evaluated using <em>in vitro</em> CCK-8 assay, flow cytometry and Transwell assay. The Western blot assay was used to evaluate the protein expression of the PPARγ pathway proteins (PPARγ, PTEN, P21, Cyclin B1, Bcl-2 and Survivin). RT-qPCR has been employed to determine the mRNA expression levels of PPARγ and PTEN. Compared to the free genistein (Free-Gen), the produced Exo-Gen demonstrated improved cellular uptake efficiency and cytotoxicity in the MG63 cell line, with half-maximal inhibitory concentrations (IC<sub>50</sub>) of 10.18 μg/mL for Free-Gen and 6.54 μg/mL for Exo-Gen. Exo-Gen substantially boosted PPARγ expression in osteosarcoma cells, relative to Free-Gen. Genistein is a non-toxic PPARγ activator which effectively inhibits the osteosarcoma cell growth when administered through exosomes. In addition, <em>in vivo</em> studies utilizing a tumour-bearing mice model corroborated the enhanced anticancer efficacy and biocompatibility of Exo-Gen. This approach significantly improves the distribution and effectiveness of genistein, rendering it as an ideal platform for future cancer therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107862"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erythritol-based co-amorphous systems for Indomethacin: Enhancing solubility, bioavailability, and therapeutic efficacy","authors":"Abhijeet A. Aher, Karimunnisa S. Shaikh","doi":"10.1016/j.jddst.2026.107987","DOIUrl":"10.1016/j.jddst.2026.107987","url":null,"abstract":"<div><div>This study explores the use of erythritol (ERY) and other co-formers, including xylitol (XYL) and biotin (BIO), in developing co-amorphous formulations (CAM) to improve the solubility, dissolution, and stability of poorly water-soluble drugs. Molecular docking revealed strong interactions between ERY and Indomethacin (IMC), supporting its role as a stabilizing co-former. Solubility parameter analysis confirmed excellent compatibility between IMC and ERY, ensuring homogeneity and preventing phase separation. The optimized IMC-ERY formulation, prepared by spray drying, achieved 99.03 % drug release within 120 min with a glass transition temperature (Tg) of 119.2 °C. Pharmacokinetic studies showed a 3.73-fold increase in bioavailability for the IMC-ERY CAM compared to crystalline IMC. Pharmacodynamic evaluation demonstrated sustained anti-inflammatory effects, with 74.25 % inhibition of paw edema at 12 h, showcasing superior performance compared to the control group and pure IMC. Histopathological analysis confirmed minimal liver and kidney toxicity, indicating the safety of the formulation. This research establishes ERY as an effective stabilizing co-former, maintaining IMC in an amorphous state, enhancing solubility, and improving therapeutic efficacy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107987"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preparation of polyethylene glycol-polycaprolactone-polyethyleneimine amphiphilic block copolymer magnetic nanocarriers for targeting treatment of hepatocellular carcinoma","authors":"Hao Wang , Minyi Zhang , Lijun You, Shaoyun Wang","doi":"10.1016/j.jddst.2026.107995","DOIUrl":"10.1016/j.jddst.2026.107995","url":null,"abstract":"<div><div>The development of multifunctional nanocarrier systems capable of achieving high drug loading, prolonged controlled release, and integrated diagnostic functions for the precise treatment of hepatocellular carcinoma represents a pressing clinical demand. This study aims to design a multifunctional nanocarrier system that combines sustained drug release, diagnostic imaging capabilities, and active tumor-targeting properties to enable synergistic therapeutic effects. A novel magnetic amphiphilic triblock copolymer (PEG-PCL-PEI) micellar nanocarrier was developed, incorporating dual-targeting mechanisms: magnetic targeting via Fe<sub>3</sub>O<sub>4</sub> nanoparticles and molecular targeting via folic acid conjugation. The system was loaded with doxorubicin (Dox) and small interfering RNA (siRNA) to achieve precise targeting of hepatic tumors. The average particle size, drug loading efficiency (LE), and encapsulation efficiency (EE) of the micelles were measured at 225 nm, 2.91 %, and 84.26 %, respectively, with a Dox release rate reaching 80 % after 35 h. The T2 relaxation rate of the formulation was determined to be 12.21 mM<sup>−1</sup> s<sup>−1</sup>, demonstrating excellent MRI contrast performance. Comprehensive evaluations of the drug delivery efficiency and <em>in vitro</em> biological activities revealed that the drug-loaded micelles inhibited the migration of human hepatocellular carcinoma HepG2 cells by 62.68 % within 24 h, indicating a strong anti-migratory effect. Furthermore, Dox induced reactive oxygen species (ROS) generation in cancer cells, while the released siRNA downregulated Bcl-2 expression, thereby synergistically promoting apoptosis in hepatocellular carcinoma cells. <em>In vivo</em> imaging and tumor inhibition studies in animal models demonstrated that the micelles significantly suppressed tumor growth without inducing notable toxicity to other organs. These findings collectively suggest that the developed micellar nanocarrier system holds substantial promise for the effective treatment of liver tumors.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107995"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qianqian Sun , Vincent Kawuribi , Yiyang Xie , Haiqing Xu , Shaohui Zheng
{"title":"CRISPR-based antimicrobials and nanomotor technologies for drug-resistant biofilms","authors":"Qianqian Sun , Vincent Kawuribi , Yiyang Xie , Haiqing Xu , Shaohui Zheng","doi":"10.1016/j.jddst.2026.108002","DOIUrl":"10.1016/j.jddst.2026.108002","url":null,"abstract":"<div><div>Antimicrobial resistance (AMR), particularly within biofilm-associated infections, has emerged as a critical global health challenge, rendering many conventional antibiotics ineffective. Two promising and rapidly evolving strategies, CRISPR-based antimicrobials and micro/nanomotor (MNM) systems, have independently shown potential in addressing this crisis. CRISPR-Cas platforms provide unmatched genetic precision, enabling selective bacterial killing or re-sensitization through the targeting of essential or resistance genes (e.g., <em>mecA</em>, <em>blaNDM-1</em>). Separately, MNMs demonstrate active penetration of biofilms, localized delivery of antimicrobials, and mechanical or chemical disruption of biofilm matrices, with propulsion mechanisms ranging from chemical fuels to magnetic and acoustic guidance. In this review, we comprehensively examine the current state of knowledge on CRISPR-based antimicrobials and nanomotor-mediated antibacterial strategies, highlighting their mechanisms, experimental advances, and limitations. We then present a perspective on their potential convergence into CRISPR-driven nanomotor systems, an emerging frontier not yet realized experimentally but conceptually poised to overcome longstanding delivery challenges. We discuss possible design frameworks, delivery strategies, and translational hurdles, while comparing this hybrid approach with existing antimicrobial delivery platforms such as bacteriophages and nanoparticles. By combining the genetic precision of CRISPR with the active penetration and controllability of nanomotors, such integrated systems may represent a next-generation paradigm for the targeted disruption of multidrug-resistant (MDR) biofilms. This article thus serves both as a comprehensive review of the current literature and a forward-looking perspective on future directions in precision antimicrobial therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108002"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}