Pub Date : 2026-03-01Epub Date: 2026-01-25DOI: 10.1016/j.jddst.2026.108062
Salma N. Hassan , Mohamed A. Abdelkhalek , Ahmed Y. Gamal , Maged A. El-Kemary , Sara A. Abdel Gaber
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 in vitro level and at the in vivo 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.
{"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}
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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-09DOI: 10.1016/j.jddst.2026.108001
Abdeslam Assafi , Lamia Hejji , Mohamed Amine Zarouki , Youssef Aoulad El Hadj Ali , Luis Pérez-Villarejo , Béla Fiser , Badredine Souhail , Abdelmonaim Azzouz
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 in-vivo and in-vitro experiments. In the in-vivo 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. In vitro experiments demonstrated strong antibacterial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) 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 IC50 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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-20DOI: 10.1016/j.jddst.2026.108029
Jing Zhang , Jing Wen , Tie Li , Junshuang Xu , Jinbiao Ma , Min Hong , Wei Li
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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-14DOI: 10.1016/j.jddst.2025.107862
Zhiqian Gu , Songou Zhang , Guoqing Li , Xudong Hu , Nanjian Xu , Yang Wang , Jian Ruan , Weihu Ma , Hong Chen
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 in vitro 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 in vitro 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 (IC50) 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, in vivo 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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-08DOI: 10.1016/j.jddst.2026.107987
Abhijeet A. Aher, Karimunnisa S. Shaikh
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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-07DOI: 10.1016/j.jddst.2026.107995
Hao Wang , Minyi Zhang , Lijun You, Shaoyun Wang
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 Fe3O4 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−1 s−1, demonstrating excellent MRI contrast performance. Comprehensive evaluations of the drug delivery efficiency and in vitro 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. In vivo 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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-09DOI: 10.1016/j.jddst.2026.108002
Qianqian Sun , Vincent Kawuribi , Yiyang Xie , Haiqing Xu , Shaohui Zheng
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., mecA, blaNDM-1). 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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-07DOI: 10.1016/j.jddst.2026.107977
Tanyaradzwa Tiandra Dembetembe , Danielle Twilley , Jacqueline Maphutha , Marco Nuno De Canha , Velaphi Clement Thipe , Vusani Mandiwana , Michel Lonji Kalombo , Rirhandzu Rikhotso , Suprakas Sinha Ray , Namrita Lall , Quenton Kritzinger
Gonorrhoea is the second most prevalent sexually transmitted disease (STD) worldwide, with its treatment increasingly compromised by antibiotic resistance to available treatments. This has led to the investigation of bioactive plants as sources for novel drug development, with plant-based nanoparticles showing promise in treating STDs. This study aimed to evaluate the anti-gonococcal activity and cytotoxicity of the ethanolic root extract of Gunnera perpensa L. (GP) and to determine whether synthesis of gold nanoparticles (AuNPs) from GP showed enhanced biological activity. Characterization of the nanoparticles was performed using ultraviolet–visible spectrometry (UV–Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), Zeta potential, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Lastly, the anti-gonococcal activity and cytotoxicity of GP and GP-AuNPs were evaluated. The AuNPs exhibited a surface plasmon resonance at 536 nm, confirming the successful synthesis of nanoparticles, with a hydrodynamic size of 127.20 nm and a core size of 39.51 nm. The GP-AuNPs showed enhanced anti-gonococcal activity compared to GP with a minimum inhibitory concentration (MIC) of 10.40 and 46.70 μg/mL, respectively. Cytotoxicity was evaluated on human keratinocytes (HaCaT), human monocytes (THP-1), and STD-related human cervical adenocarcinoma (HeLa), with GP-AuNPs exhibiting fifty percent inhibitory concentrations (IC50) of 22.12 ± 0.52, 27.53 ± 6.02, and >38.96 μg/mL, respectively. In contrast, GP showed IC50 values > 400 μg/mL against all tested cell lines. These findings indicate that GP-AuNPs exhibit significant anti-gonococcal activity with greater selectivity for Neisseria gonorrhoeae over non-cancerous (HaCaT and THP-1) cells, as evidenced by selectivity indices (SIs) > 2. These findings suggest that both GP and GP-AuNP possess potential as lead candidates for the treatment of gonorrhoea. Their limited antiproliferative activity against HeLa cells (SI < 0.7) indicates they are unsuitable for treating STD-associated cervical cancers. To the best of our knowledge, no published studies have investigated the effect of plant-synthesized nanoparticles on their activity against N. gonorrhoeae; therefore, this is the first use of GP-AuNPs against N. gonorrhoeae, advancing plant-based nanomedicine for STDs.
{"title":"Gunnera perpensa L. - mediated gold nanoparticles with enhanced anti-gonococcal activity","authors":"Tanyaradzwa Tiandra Dembetembe , Danielle Twilley , Jacqueline Maphutha , Marco Nuno De Canha , Velaphi Clement Thipe , Vusani Mandiwana , Michel Lonji Kalombo , Rirhandzu Rikhotso , Suprakas Sinha Ray , Namrita Lall , Quenton Kritzinger","doi":"10.1016/j.jddst.2026.107977","DOIUrl":"10.1016/j.jddst.2026.107977","url":null,"abstract":"<div><div>Gonorrhoea is the second most prevalent sexually transmitted disease (STD) worldwide, with its treatment increasingly compromised by antibiotic resistance to available treatments. This has led to the investigation of bioactive plants as sources for novel drug development, with plant-based nanoparticles showing promise in treating STDs. This study aimed to evaluate the anti-gonococcal activity and cytotoxicity of the ethanolic root extract of <em>Gunnera perpensa</em> L. (GP) and to determine whether synthesis of gold nanoparticles (AuNPs) from GP showed enhanced biological activity. Characterization of the nanoparticles was performed using ultraviolet–visible spectrometry (UV–Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), Zeta potential, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Lastly, the anti-gonococcal activity and cytotoxicity of GP and GP-AuNPs were evaluated. The AuNPs exhibited a surface plasmon resonance at 536 nm, confirming the successful synthesis of nanoparticles, with a hydrodynamic size of 127.20 nm and a core size of 39.51 nm. The GP-AuNPs showed enhanced anti-gonococcal activity compared to GP with a minimum inhibitory concentration (MIC) of 10.40 and 46.70 μg/mL, respectively. Cytotoxicity was evaluated on human keratinocytes (HaCaT), human monocytes (THP-1), and STD-related human cervical adenocarcinoma (HeLa), with GP-AuNPs exhibiting fifty percent inhibitory concentrations (IC<sub>50</sub>) of 22.12 ± 0.52, 27.53 ± 6.02, and >38.96 μg/mL, respectively. In contrast, GP showed IC<sub>50</sub> values > 400 μg/mL against all tested cell lines. These findings indicate that GP-AuNPs exhibit significant anti-gonococcal activity with greater selectivity for <em>Neisseria gonorrhoeae</em> over non-cancerous (HaCaT and THP-1) cells, as evidenced by selectivity indices (SIs) > 2. These findings suggest that both GP and GP-AuNP possess potential as lead candidates for the treatment of gonorrhoea. Their limited antiproliferative activity against HeLa cells (SI < 0.7) indicates they are unsuitable for treating STD-associated cervical cancers. To the best of our knowledge, no published studies have investigated the effect of plant-synthesized nanoparticles on their activity against <em>N. gonorrhoeae</em>; therefore, this is the first use of GP-AuNPs against <em>N. gonorrhoeae</em>, advancing plant-based nanomedicine for STDs.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107977"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980900","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}
Targeted drug delivery systems are crucial for cancer treatment, as they boost therapeutic effectiveness while minimizing systemic toxicity. In this study, we developed pH-degradable hollow mesoporous silica nanoparticles (HMON) functionalized with hyaluronic acid (HA) for CD44-targeted drug delivery. Aryl imine organosilane was utilized to confer pH-responsiveness to the HMON, enabling controlled drug release in the mildly acidic tumor microenvironment. In vitro studies have shown that DOX@HMON-HA significantly enhances DOX uptake in CD44-overexpressing tumor cells, such as HeLa and HCT-116, leading to substantial cytotoxic effects. In contrast, CD44-low expressing cells like MCF-7 exhibit minimal DOX uptake and reduced cytotoxicity. In vivo studies further validated the therapeutic efficacy of DOX@HMON-HA, showing effective tumor growth suppression without observable systemic toxicity. These findings underscore the potential of pH-degradable hyaluronan (HA)-modified silica nanoparticles as an effective strategy for targeted cancer therapy.
{"title":"CD44-targeted and pH-degradable hollow mesoporous silica nanocarriers for cancer therapy","authors":"Yi-Ching Tsai , Natesan Thirumalaivasan , Shu-Pao Wu","doi":"10.1016/j.jddst.2026.108045","DOIUrl":"10.1016/j.jddst.2026.108045","url":null,"abstract":"<div><div>Targeted drug delivery systems are crucial for cancer treatment, as they boost therapeutic effectiveness while minimizing systemic toxicity. In this study, we developed pH-degradable hollow mesoporous silica nanoparticles (HMON) functionalized with hyaluronic acid (HA) for CD44-targeted drug delivery. Aryl imine organosilane was utilized to confer pH-responsiveness to the HMON, enabling controlled drug release in the mildly acidic tumor microenvironment. In vitro studies have shown that <strong>DOX@HMON-HA</strong> significantly enhances DOX uptake in CD44-overexpressing tumor cells, such as HeLa and HCT-116, leading to substantial cytotoxic effects. In contrast, CD44-low expressing cells like MCF-7 exhibit minimal DOX uptake and reduced cytotoxicity. In vivo studies further validated the therapeutic efficacy of <strong>DOX@HMON-HA</strong>, showing effective tumor growth suppression without observable systemic toxicity. These findings underscore the potential of pH-degradable hyaluronan (HA)-modified silica nanoparticles as an effective strategy for targeted cancer therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108045"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035466","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}