Pub Date : 2026-01-15DOI: 10.1016/j.jddst.2026.108024
Jesús Quezada-Urbina , Edna Vázquez-Vélez , Carlos J. Villagómez , Josselyne Transito-Medina , Victor M. Castaño
Electrospun nanofibers have attracted considerable attention due to their unique physicochemical properties and broad range of applications, particularly in biomedical applications. Non-Thermal Plasma (NTP) treatment has emerged as a versatile tool for tailoring both the properties of polymer solutions before electrospinning and the characteristics of the resulting nanofibers. When applied to polymer solutions, NTP alters essential parameters such as viscosity, ionic conductivity, and surface tension through dipole-dipole and ion-dipole interactions between plasma ions and solvent or polymer molecules. These interactions facilitate the expansion of polymer coils, thereby improving electrospinnability. As a result, the nanofibers produced exhibit superior morphological, mechanical, and physicochemical properties. NTP treatment enhances the performance of nanofiber surfaces by increasing hydrophilicity, biocompatibility, and surface reactivity. Nevertheless, optimizing plasma parameters to achieve reproducible results remains a significant challenge. This article reviews recent advancements in NTP-assisted electrospinning, highlighting its potential to produce functional nanofibers for biomedical applications, including bioactive scaffolds, antimicrobial dressings, and controlled drug-delivery systems. Furthermore, it positions NTP as an influential tool for regenerative medicine and wound healing.
{"title":"Plasma-assisted electrospinning of functional nanofibers: Solution and surface nanoengineering for biomedical applications","authors":"Jesús Quezada-Urbina , Edna Vázquez-Vélez , Carlos J. Villagómez , Josselyne Transito-Medina , Victor M. Castaño","doi":"10.1016/j.jddst.2026.108024","DOIUrl":"10.1016/j.jddst.2026.108024","url":null,"abstract":"<div><div>Electrospun nanofibers have attracted considerable attention due to their unique physicochemical properties and broad range of applications, particularly in biomedical applications. Non-Thermal Plasma (NTP) treatment has emerged as a versatile tool for tailoring both the properties of polymer solutions before electrospinning and the characteristics of the resulting nanofibers. When applied to polymer solutions, NTP alters essential parameters such as viscosity, ionic conductivity, and surface tension through dipole-dipole and ion-dipole interactions between plasma ions and solvent or polymer molecules. These interactions facilitate the expansion of polymer coils, thereby improving electrospinnability. As a result, the nanofibers produced exhibit superior morphological, mechanical, and physicochemical properties. NTP treatment enhances the performance of nanofiber surfaces by increasing hydrophilicity, biocompatibility, and surface reactivity. Nevertheless, optimizing plasma parameters to achieve reproducible results remains a significant challenge. This article reviews recent advancements in NTP-assisted electrospinning, highlighting its potential to produce functional nanofibers for biomedical applications, including bioactive scaffolds, antimicrobial dressings, and controlled drug-delivery systems. Furthermore, it positions NTP as an influential tool for regenerative medicine and wound healing.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108024"},"PeriodicalIF":4.9,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035341","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 : 2026-01-14DOI: 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":"2026-01-14","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 : 2026-01-14DOI: 10.1016/j.jddst.2026.108022
Allexia Passos Souza, Jeremy Marston
Intra-muscular (IM) injection via hypodermic needle and syringe is the most common delivery method of vaccines due to the muscle tissue ability to receive large volumes, high degree of vascularization, and tolerance of needle insertion. When injections are augmented with enabling technologies such as electroporation (EP), the drug dispersion zone becomes an important consideration since it should match with the electric field generated by the EP device. Herein, we sought to modify the flow from a standard hypodermic by implementing multiple side-ports along the length of the needle. We evaluated the flow in these side-port designs using CFD simulations and experimental validation. Our results indicate that low flow rates ( mL/min, ) result in non-uniform flow distribution, while higher flow rates ( mL/min, ) result in near-uniform distribution of flow along all the side-ports, potentially creating superior drug dispersion pattern along the needle length for improved cellular uptake with EP.
{"title":"Evaluation of multi-port needles for enhanced intramuscular drug delivery via experimental and CFD models","authors":"Allexia Passos Souza, Jeremy Marston","doi":"10.1016/j.jddst.2026.108022","DOIUrl":"10.1016/j.jddst.2026.108022","url":null,"abstract":"<div><div>Intra-muscular (IM) injection via hypodermic needle and syringe is the most common delivery method of vaccines due to the muscle tissue ability to receive large volumes, high degree of vascularization, and tolerance of needle insertion. When injections are augmented with enabling technologies such as electroporation (EP), the drug dispersion zone becomes an important consideration since it should match with the electric field generated by the EP device. Herein, we sought to modify the flow from a standard hypodermic by implementing multiple side-ports along the length of the needle. We evaluated the flow in these side-port designs using CFD simulations and experimental validation. Our results indicate that low flow rates (<span><math><mrow><mi>Q</mi><mo><</mo><mn>10</mn></mrow></math></span> mL/min, <span><math><mrow><mi>R</mi><mi>e</mi><mo>=</mo><mn>4</mn><mi>ρ</mi><mi>Q</mi><mo>/</mo><mi>π</mi><mi>d</mi><mi>μ</mi><mo>≲</mo><mn>500</mn></mrow></math></span>) result in non-uniform flow distribution, while higher flow rates (<span><math><mrow><mi>Q</mi><mo>≳</mo><mn>15</mn></mrow></math></span> mL/min, <span><math><mrow><mi>R</mi><mi>e</mi><mo>≳</mo><mn>769</mn></mrow></math></span>) result in near-uniform distribution of flow along all the side-ports, potentially creating superior drug dispersion pattern along the needle length for improved cellular uptake with EP.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108022"},"PeriodicalIF":4.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035463","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 : 2026-01-14DOI: 10.1016/j.jddst.2026.108018
Ana Claudia Pedrozo da Silva , Camila Fabiano de Freitas , Italo Rodrigo Calori , Antonio Claudio Tedesco , Amanda Gratão Silvestrin , Leandro Herculano da Silva , Maria Ida Bonini Ravanelli Speziali , Noboru Hioka , André Luiz Tessaro
Multidrug systems offer a promising strategy to improve the efficacy of anticancer treatments, reduce therapeutic doses, and attenuate side effects. In this study, the photosensitizers Azure A (AA) and rose bengal decyl ester (RBDEC) were co-encapsulated in hybrid DPPC/F127 liposomes to target multiple cellular sites. The combined system yielded small unilamellar vesicles (SUVs) with a polydispersity index suitable for biological applications and a zeta potential of +10.57 mV. The encapsulation efficiency of AA and RBDEC is 60.3 and 98.5 %, respectively. In the colorectal adenocarcinoma Caco-2 cells line, photosensitizers showed distinct cellular localization, with RBDEC most targeting the nuclear region and AA the cytoplasm confirmed by confocal microscopy. According to the Chou–Talalay method for drug combinations, the equimolar and lower concentrations (2.5 × 10−6 mol L−1 each) exhibited an additive effect, suggesting that even lower concentrations could achieve synergism. The findings indicate that this system exhibits considerable promise, as the combination of drugs facilitates action at multiple sites, thereby increasing the likelihood of cell death. In addition, the system demonstrated greater efficiency at lower concentrations, reducing adverse effects and directing future studies.
多药系统为提高抗癌治疗的疗效、减少治疗剂量和减轻副作用提供了一种很有前途的策略。在这项研究中，光敏剂Azure A （AA）和玫瑰红脱酯（RBDEC）被共包被在DPPC/F127杂交脂质体中，以靶向多个细胞位点。该组合体系制备的单层小囊泡（suv）具有适合生物应用的多分散性指数，zeta电位为+10.57 mV。AA和RBDEC的包封率分别为60.3%和98.5%。在结直肠癌Caco-2细胞系中，光敏剂表现出明显的细胞定位，共聚焦显微镜证实RBDEC主要靶向核区，AA主要靶向细胞质。根据Chou-Talalay方法，等摩尔浓度和较低浓度（各2.5 × 10−6 mol L−1）表现出加性效应，表明较低浓度也能实现协同作用。研究结果表明，该系统显示出相当大的前景，因为药物组合促进了多个位点的作用，从而增加了细胞死亡的可能性。此外，该系统在较低浓度下表现出更高的效率，减少了不利影响，并指导了未来的研究。
{"title":"Liposomal co-formulation of Azure A and rose bengal decyl ester as a multi-cellular target approach for photodynamic therapy of colorectal cancer","authors":"Ana Claudia Pedrozo da Silva , Camila Fabiano de Freitas , Italo Rodrigo Calori , Antonio Claudio Tedesco , Amanda Gratão Silvestrin , Leandro Herculano da Silva , Maria Ida Bonini Ravanelli Speziali , Noboru Hioka , André Luiz Tessaro","doi":"10.1016/j.jddst.2026.108018","DOIUrl":"10.1016/j.jddst.2026.108018","url":null,"abstract":"<div><div>Multidrug systems offer a promising strategy to improve the efficacy of anticancer treatments, reduce therapeutic doses, and attenuate side effects. In this study, the photosensitizers Azure A (AA) and rose bengal decyl ester (RBDEC) were co-encapsulated in hybrid DPPC/F127 liposomes to target multiple cellular sites. The combined system yielded small unilamellar vesicles (SUVs) with a polydispersity index suitable for biological applications and a zeta potential of +10.57 mV. The encapsulation efficiency of AA and RBDEC is 60.3 and 98.5 %, respectively. In the colorectal adenocarcinoma Caco-2 cells line, photosensitizers showed distinct cellular localization, with RBDEC most targeting the nuclear region and AA the cytoplasm confirmed by confocal microscopy. According to the Chou–Talalay method for drug combinations, the equimolar and lower concentrations (2.5 × 10<sup>−6</sup> mol L<sup>−1</sup> each) exhibited an additive effect, suggesting that even lower concentrations could achieve synergism. The findings indicate that this system exhibits considerable promise, as the combination of drugs facilitates action at multiple sites, thereby increasing the likelihood of cell death. In addition, the system demonstrated greater efficiency at lower concentrations, reducing adverse effects and directing future studies.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108018"},"PeriodicalIF":4.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035372","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 : 2026-01-14DOI: 10.1016/j.jddst.2026.108021
Hafiz Muhammad Junaid Shoukat , Fatima Akbar Sheikh , Muhammad Tayyab , Syed Nasir Abbas Bukhari , Muhammad Tahir Haseeb , Imran Nazir , Ranya Abdulrahman Alafar , Mohamed Abdelwahab Abdelgawad , Mohammad M. Al-Sanea , Ameeduzzafar Zafar , Naveed Ahmad
The current study reported the preparation of Febuxostat (FBS) nanosuspension (Ns) and then incorporation in an orodispersible film (ODF) based on naturally occurring swellable polysaccharide, i.e., quince seed polysaccharide (QSP). Central composite design was employed to determine the interactive effects of independent variables (polymer and plasticizer concentrations) on the response variables (swelling index, disintegration time, and dissolution time) and select the optimized formulation. The FBS-Ns and FBS-Ns-ODFs were evaluated through dynamic light scattering (DLS), physico-chemical and mechanical parameters, FTIR, PXRD, SEM, AFM, contact angle determination, and in vitro and in vivo drug release studies. The particle size of the FBS-Ns was recorded as 720 nm, and they were uniformly and homogenously distributed in the ODFs as revealed through DLS, PXRD, AFM, and SEM images. The contact angle determination revealed a highly hydrophilic surface of the film that facilitated the FBS release from FBS-Ns-ODFs within 10 min at pH 6.8. The pharmacokinetics study revealed an increase in the relative bioavailability by 147.15 %. These results indicated that the FBS-Ns-ODF provided a potential opportunity to transform FBS-Ns into a solid unit dosage form, i.e., ODF, to improve the dissolution profile and enhance the oral bioavailability of a poorly water-soluble drug.
{"title":"Statistically optimized orodispersible film loaded with Febuxostat nanosuspension to enhance oral bioavailability","authors":"Hafiz Muhammad Junaid Shoukat , Fatima Akbar Sheikh , Muhammad Tayyab , Syed Nasir Abbas Bukhari , Muhammad Tahir Haseeb , Imran Nazir , Ranya Abdulrahman Alafar , Mohamed Abdelwahab Abdelgawad , Mohammad M. Al-Sanea , Ameeduzzafar Zafar , Naveed Ahmad","doi":"10.1016/j.jddst.2026.108021","DOIUrl":"10.1016/j.jddst.2026.108021","url":null,"abstract":"<div><div>The current study reported the preparation of Febuxostat (FBS) nanosuspension (Ns) and then incorporation in an orodispersible film (ODF) based on naturally occurring swellable polysaccharide, i.e., quince seed polysaccharide (QSP). Central composite design was employed to determine the interactive effects of independent variables (polymer and plasticizer concentrations) on the response variables (swelling index, disintegration time, and dissolution time) and select the optimized formulation. The FBS-Ns and FBS-Ns-ODFs were evaluated through dynamic light scattering (DLS), physico-chemical and mechanical parameters, FTIR, PXRD, SEM, AFM, contact angle determination, and <em>in vitro</em> and <em>in vivo</em> drug release studies. The particle size of the FBS-Ns was recorded as 720 nm, and they were uniformly and homogenously distributed in the ODFs as revealed through DLS, PXRD, AFM, and SEM images. The contact angle determination revealed a highly hydrophilic surface of the film that facilitated the FBS release from FBS-Ns-ODFs within 10 min at pH 6.8. The pharmacokinetics study revealed an increase in the relative bioavailability by 147.15 %. These results indicated that the FBS-Ns-ODF provided a potential opportunity to transform FBS-Ns into a solid unit dosage form, i.e., ODF, to improve the dissolution profile and enhance the oral bioavailability of a poorly water-soluble drug.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108021"},"PeriodicalIF":4.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035375","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}
Sorafenib (SOR) is a commonly used medication to treat advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is limited by poor water solubility, fast metabolism, and undesirable side effects. While milk and red blood cells (RBCs) have been introduced as potentially safe, scalable, and available sources of extracellular vesicles (EVs), no study has compared the feasibility of milk-derived EVs (miEVs) and RBC-derived EVs (RBCEVs) as drug delivery vehicles. Moreover, there is little information on whether loading SOR into EVs improves its therapeutic effectiveness. Herein, we isolated RBCEVs at 100,000×g (RBCEV100K) and various subpopulations of miEVs at 35,000×g (miEV35K), 70,000×g (miEV70K), and 100,000×g (miEV100K), and characterized them based on marker expression and size distribution. SOR was subsequently loaded into these EVs via incubation, and encapsulation efficiency was measured spectrophotometrically. Storage stability and cellular uptake were also assessed. Furthermore, comprehensive in vitro and in vivo assessments were performed on hepatic cell lines, Huh-7 and Hep3B. The isolated EVs were <200 nm in size and positive for EV-specific protein markers. Compared to the other EVs, miEV100K exhibited considerably higher SOR loading. Moreover, its stability during storage and cellular uptake rate in both cell lines were more efficient than RBCEV100K. Therefore, as an optimal SOR carrier, miEV100K was selected for subsequent experiments. Compared to SOR, SOR-miEV100K significantly induced apoptosis and inhibited proliferation, cell cycle progression, colony formation, and migration capacities in HCC cells by downregulating CDH2, Ki-67, CCND1, and CD133, while upregulating P53 expression. Moreover, SOR-miEV100K significantly attenuated the tumorigenic potential of Huh-7 cells in nude mice and was less cytotoxic to normal human fibroblasts than SOR. Therefore, miEV100K not only enhances the therapeutic efficacy of SOR but also reduces its side effects, highlighting its promise as a delivery platform. However, further investigation is required to pave the way toward clinical application.
{"title":"Milk-derived extracellular vesicles enhanced Sorafenib's therapeutic response on hepatocellular carcinoma cells","authors":"Mahsa Salehi , Babak Negahdari , Mahdieh Hashemi , Homeyra Seydi , Sareh Salarinejad , Abbas Piryaei , Alimohamad Moradi , Ali Zarrabi , Faezeh Shekari , Massoud Vosough","doi":"10.1016/j.jddst.2026.108005","DOIUrl":"10.1016/j.jddst.2026.108005","url":null,"abstract":"<div><div>Sorafenib (SOR) is a commonly used medication to treat advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is limited by poor water solubility, fast metabolism, and undesirable side effects. While milk and red blood cells (RBCs) have been introduced as potentially safe, scalable, and available sources of extracellular vesicles (EVs), no study has compared the feasibility of milk-derived EVs (miEVs) and RBC-derived EVs (RBCEVs) as drug delivery vehicles. Moreover, there is little information on whether loading SOR into EVs improves its therapeutic effectiveness. Herein, we isolated RBCEVs at 100,000×<em>g</em> (RBCEV100K) and various subpopulations of miEVs at 35,000×<em>g</em> (miEV35K), 70,000×<em>g</em> (miEV70K), and 100,000×<em>g</em> (miEV100K), and characterized them based on marker expression and size distribution. SOR was subsequently loaded into these EVs via incubation, and encapsulation efficiency was measured spectrophotometrically. Storage stability and cellular uptake were also assessed. Furthermore, comprehensive <em>in vitro</em> and <em>in vivo</em> assessments were performed on hepatic cell lines, Huh-7 and Hep3B. The isolated EVs were <200 nm in size and positive for EV-specific protein markers. Compared to the other EVs, miEV100K exhibited considerably higher SOR loading. Moreover, its stability during storage and cellular uptake rate in both cell lines were more efficient than RBCEV100K. Therefore, as an optimal SOR carrier, miEV100K was selected for subsequent experiments. Compared to SOR, SOR-miEV100K significantly induced apoptosis and inhibited proliferation, cell cycle progression, colony formation, and migration capacities in HCC cells by downregulating <em>CDH2, Ki-67, CCND1</em>, and <em>CD133</em>, while upregulating <em>P53</em> expression. Moreover, SOR-miEV100K significantly attenuated the tumorigenic potential of Huh-7 cells in nude mice and was less cytotoxic to normal human fibroblasts than SOR. Therefore, miEV100K not only enhances the therapeutic efficacy of SOR but also reduces its side effects, highlighting its promise as a delivery platform. However, further investigation is required to pave the way toward clinical application.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108005"},"PeriodicalIF":4.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980828","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 : 2026-01-13DOI: 10.1016/j.jddst.2026.108000
Arshad Islam , Khizar Abdullah Khan , Asma Ashraf , Anwar Ullah , Muhammad Tariq , Ajmal Khan , Suliman Syed , Ikram Ullah , Amir Muhammad
This study compares the dose- and time-dependent antileishmanial efficacy of chemically synthesized (Ch-FeO-NPs) and green-synthesized (Gr-FeO-NPs) iron oxide nanoparticles using Trigonella foenum-graecum seed extract under photodynamic therapy. FTIR and UV–vis confirmed synthesis, while XRD and SEM showed Gr-FeO-NPs were rod-shaped (21.25 nm), and Ch-FeO-NPs were spherical (27.45 nm). In vitro assays against Leishmania tropica promastigotes and intramacrophagic amastigotes showed Gr-FeO-NPs had superior activity, especially with 15 min LED pre-incubation. After 72 h, Gr-FeO-NPs exhibited an IC50 of 0.038 ± 0.004 μg/mL against promastigotes, much lower than Ch-FeO-NPs (12.8 ± 1.61 μg/mL; p < 0.0001). Without LED, Gr-FeO-NPs remained more effective (IC50 25.77 ± 1.18 μg/mL) than Ch-FeO-NPs (36.09 ± 1.69 μg/mL). Against amastigotes, Gr-FeO-NPs again outperformed under LED (IC50 0.074 ± 0.04 μg/mL vs. 21.68 ± 0.7 μg/mL; p < 0.0001). Their enhanced efficacy is linked to greater ROS generation, DNA damage, membrane disruption, and apoptosis. Gr-FeO-NPs were also less cytotoxic to murine macrophages (CC50 423.6 ± 4.1 μg/mL) than Ch-FeO-NPs (51.35 ± 2.5 μg/mL). At 72 h, Gr-FeO-NPs had a selectivity index (SI) of 2647.3 vs. 1.1 for Ch-FeO-NPs. These results support Gr-FeO-NPs as a potent and biocompatible candidate for leishmaniasis photodynamic therapy.
本研究比较了化学合成（Ch-FeO-NPs）和绿色合成（Gr-FeO-NPs）氧化铁纳米颗粒在光动力治疗下抗利什曼病的剂量依赖性和时间依赖性。FTIR和UV-vis证实了合成，XRD和SEM显示Gr-FeO-NPs为棒状（21.25 nm）， Ch-FeO-NPs为球形（27.45 nm）。体外抗热带利什曼原虫原鞭毛菌和巨噬性无鞭毛菌实验表明，Gr-FeO-NPs具有较好的活性，特别是在LED预孵育15 min时。72h后，Gr-FeO-NPs对proprotigotes的IC50为0.038±0.004 μg/mL，远低于Ch-FeO-NPs（12.8±1.61 μg/mL; p < 0.0001）。未添加LED时，Gr-FeO-NPs的IC50（25.77±1.18 μg/mL）高于Ch-FeO-NPs（36.09±1.69 μg/mL）。对无纺丝菌，Gr-FeO-NPs在LED下的表现再次优于无纺丝菌（IC50为0.074±0.04 μg/mL vs. 21.68±0.7 μg/mL; p < 0.0001）。其增强的功效与更多的ROS生成、DNA损伤、膜破坏和细胞凋亡有关。Gr-FeO-NPs对小鼠巨噬细胞的细胞毒性（CC50为423.6±4.1 μg/mL）也低于Ch-FeO-NPs（51.35±2.5 μg/mL）。72h时，Gr-FeO-NPs的选择性指数（SI）为2647.3，Ch-FeO-NPs为1.1。这些结果支持Gr-FeO-NPs作为利什曼病光动力治疗的有效和生物相容性候选物。
{"title":"Photodynamic therapy-enhanced antileishmanial efficacy and biocompatibility of chemically and green-synthesized iron oxide nanoparticles: An in vitro dose- and time-dependent comparative study","authors":"Arshad Islam , Khizar Abdullah Khan , Asma Ashraf , Anwar Ullah , Muhammad Tariq , Ajmal Khan , Suliman Syed , Ikram Ullah , Amir Muhammad","doi":"10.1016/j.jddst.2026.108000","DOIUrl":"10.1016/j.jddst.2026.108000","url":null,"abstract":"<div><div>This study compares the dose- and time-dependent antileishmanial efficacy of chemically synthesized (Ch-FeO-NPs) and green-synthesized (Gr-FeO-NPs) iron oxide nanoparticles using <em>Trigonella foenum-graecum</em> seed extract under photodynamic therapy. FTIR and UV–vis confirmed synthesis, while XRD and SEM showed Gr-FeO-NPs were rod-shaped (21.25 nm), and Ch-FeO-NPs were spherical (27.45 nm). In vitro assays against <em>Leishmania tropica</em> promastigotes and intramacrophagic amastigotes showed Gr-FeO-NPs had superior activity, especially with 15 min LED pre-incubation. After 72 h, Gr-FeO-NPs exhibited an IC<sub>50</sub> of 0.038 ± 0.004 μg/mL against promastigotes, much lower than Ch-FeO-NPs (12.8 ± 1.61 μg/mL; p < 0.0001). Without LED, Gr-FeO-NPs remained more effective (IC<sub>50</sub> 25.77 ± 1.18 μg/mL) than Ch-FeO-NPs (36.09 ± 1.69 μg/mL). Against amastigotes, Gr-FeO-NPs again outperformed under LED (IC<sub>50</sub> 0.074 ± 0.04 μg/mL vs. 21.68 ± 0.7 μg/mL; p < 0.0001). Their enhanced efficacy is linked to greater ROS generation, DNA damage, membrane disruption, and apoptosis. Gr-FeO-NPs were also less cytotoxic to murine macrophages (CC<sub>50</sub> 423.6 ± 4.1 μg/mL) than Ch-FeO-NPs (51.35 ± 2.5 μg/mL). At 72 h, Gr-FeO-NPs had a selectivity index (SI) of 2647.3 vs. 1.1 for Ch-FeO-NPs. These results support Gr-FeO-NPs as a potent and biocompatible candidate for leishmaniasis photodynamic therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108000"},"PeriodicalIF":4.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980387","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 : 2026-01-13DOI: 10.1016/j.jddst.2026.108017
Qianqian Liu , Yusong Pan , Peixuan Zou , Ling Peng , Cuilian Wei , Wenjie Luo , Run Huang , Xiuling Lin , Jun Tao
This study overcomes intracellular antioxidant barriers limiting chemodynamic therapy (CDT) by designing an Fe-Cu bimetallic organic framework (MOF) nanocarrier. Synthesized solvothermally, the spindle-shaped MOF (long axis: 3.5 μm; short axis: 2 μm) exhibits a high specific surface area (381.96 m2/g) and mesopores (6.69 nm diameter), as verified by SEM/XRD/FT-IR/BET/XPS. The coexisting Fe3+/Fe2+ and Cu2+ sites enable synergistic catalysis, achieving 68.2 ± 2.1 % doxorubicin (DOX) loading with pH-responsive release in tumor-mimetic acidosis (pH 5.4; 78 % cumulative release at 72 h, 7.8 × higher than neutral pH). In vitro studies confirm dual functions: efficient glutathione depletion (60 % absorbance reduction at pH 6.2, 300 μg/mL MOF) and enhanced hydroxyl radical generation via Fenton/Fenton-like reactions (40 × TMB absorbance increase). Cell assays demonstrate low cytotoxicity to normal 293T cells within 48 h (>80 % viability at 25 μg/mL) versus potent synergistic efficacy against HeLa cells under simulated tumor microenvironment (100 μM H2O2), where chemo-CDT reduces viability to 35 % (31.4–37.5 % improvement over monotherapies). This work establishes a self-driven platform for tumor-targeted synergistic therapy.
{"title":"Fe-Cu bimetallic organic framework overcomes antioxidant barriers to achieve synergistic chemo-chemodynamic tumor therapy","authors":"Qianqian Liu , Yusong Pan , Peixuan Zou , Ling Peng , Cuilian Wei , Wenjie Luo , Run Huang , Xiuling Lin , Jun Tao","doi":"10.1016/j.jddst.2026.108017","DOIUrl":"10.1016/j.jddst.2026.108017","url":null,"abstract":"<div><div>This study overcomes intracellular antioxidant barriers limiting chemodynamic therapy (CDT) by designing an Fe-Cu bimetallic organic framework (MOF) nanocarrier. Synthesized solvothermally, the spindle-shaped MOF (long axis: 3.5 μm; short axis: 2 μm) exhibits a high specific surface area (381.96 m<sup>2</sup>/g) and mesopores (6.69 nm diameter), as verified by SEM/XRD/FT-IR/BET/XPS. The coexisting Fe<sup>3+</sup>/Fe<sup>2+</sup> and Cu<sup>2+</sup> sites enable synergistic catalysis, achieving 68.2 ± 2.1 % doxorubicin (DOX) loading with pH-responsive release in tumor-mimetic acidosis (pH 5.4; 78 % cumulative release at 72 h, 7.8 × higher than neutral pH). In vitro studies confirm dual functions: efficient glutathione depletion (60 % absorbance reduction at pH 6.2, 300 μg/mL MOF) and enhanced hydroxyl radical generation via Fenton/Fenton-like reactions (40 × TMB absorbance increase). Cell assays demonstrate low cytotoxicity to normal 293T cells within 48 h (>80 % viability at 25 μg/mL) versus potent synergistic efficacy against HeLa cells under simulated tumor microenvironment (100 μM H<sub>2</sub>O<sub>2</sub>), where chemo-CDT reduces viability to 35 % (31.4–37.5 % improvement over monotherapies). This work establishes a self-driven platform for tumor-targeted synergistic therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108017"},"PeriodicalIF":4.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035460","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}
Glioblastoma multiforme (GBM) is characterized by a poor clinical prognosis, with conventional therapies offering limited effectiveness. To address this challenge, the current study presents a mitochondrial-targeted approach wherein a naturally occurring plant cytokinin, kinetin riboside (KR), was incorporated into dequalinium (DQA)-based vesicles, also called DQAsomes. The present study aims to develop and optimize KR-loaded DQAsomes using a Quality-by-Design (QbD) approach for intranasal delivery, including screening of factors by Plackett-Burman design followed by optimization through Box-Behnken Design. The optimized DQAsomes had a particle size of 203 nm, a polydispersity index of 0.17, zeta potential of 32.80 mV and a 74.15 % entrapment efficiency. In vitro drug release in pH 6.8 phosphate buffer demonstrated sustained release in comparison to free KR solution. Ex vivo studies further confirmed improved KR permeation from KR-loaded DQAsomes (1501.73 ± 1.21 μg/cm2) than from KR solution (1149.81 ± 9.20 μg/cm2) across the nasal mucosa. The optimized DQAsomes exhibited superior anticancer activity in the glioma cell line (U87G), as evidenced by a markedly lower IC50 value for KR-loaded DQAsomes (9.64 μM) compared to free KR solution (32.33 μM) and DQA solution (68.20 μM). Further apoptosis assay and cell cycle assay revealed superior anticancer potential of KR-loaded DQAsomes. In summary, this research introduces a promising, non-invasive alternative to current GBM treatment, enabling delivery of KR through a systematic QbD approach.
{"title":"Optimization and characterization of vesicular carrier for nose to brain delivery in glioblastoma therapy-part I","authors":"Tejas Girish Agnihotri , Nidhi Singh , Shyam Sudhakar Gomte , Hemant Kumar , Aakanchha Jain","doi":"10.1016/j.jddst.2026.108004","DOIUrl":"10.1016/j.jddst.2026.108004","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is characterized by a poor clinical prognosis, with conventional therapies offering limited effectiveness. To address this challenge, the current study presents a mitochondrial-targeted approach wherein a naturally occurring plant cytokinin, kinetin riboside (KR), was incorporated into dequalinium (DQA)-based vesicles, also called DQAsomes. The present study aims to develop and optimize KR-loaded DQAsomes using a Quality-by-Design (QbD) approach for intranasal delivery, including screening of factors by Plackett-Burman design followed by optimization through Box-Behnken Design. The optimized DQAsomes had a particle size of 203 nm, a polydispersity index of 0.17, zeta potential of 32.80 mV and a 74.15 % entrapment efficiency. <em>In vitro</em> drug release in pH 6.8 phosphate buffer demonstrated sustained release in comparison to free KR solution. <em>Ex vivo</em> studies further confirmed improved KR permeation from KR-loaded DQAsomes (1501.73 ± 1.21 μg/cm<sup>2</sup>) than from KR solution (1149.81 ± 9.20 μg/cm<sup>2</sup>) across the nasal mucosa. The optimized DQAsomes exhibited superior anticancer activity in the glioma cell line (U87G), as evidenced by a markedly lower IC<sub>50</sub> value for KR-loaded DQAsomes (9.64 μM) compared to free KR solution (32.33 μM) and DQA solution (68.20 μM). Further apoptosis assay and cell cycle assay revealed superior anticancer potential of KR-loaded DQAsomes. In summary, this research introduces a promising, non-invasive alternative to current GBM treatment, enabling delivery of KR through a systematic QbD approach.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108004"},"PeriodicalIF":4.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980388","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}
While Food and Drug Administration (FDA)-approved prophylactic human papillomavirus (HPV) vaccines are available, their inability to treat existing infections highlights the urgent need for therapeutic vaccines targeting pre-existing infections. DNA-based vaccines represent a promising solution; however, their weak immunogenicity necessitates an effective delivery system. Cell-penetrating peptides (CPPs) are powerful vectors for DNA delivery, offering several advantages over viral vectors. This study examines the potential of the CPP DOT1L to enhance the delivery and efficacy of an HPV L1-E7 multi-epitope DNA vaccine using integrated in silico, in vitro, and in vivo approaches. In silico studies, molecular docking revealed that DOT1L binds to the DNA duplex via interactions between its Arginine and Lysine residues and the DNA major groove. The CPP DOT1L also has a strong affinity for the membrane due to these positively charged residues. Molecular Dynamics simulations indicated that DOT1L can efficiently penetrate the membrane, while the DNA duplex has limited interfacial interactions. In vitro experiments confirmed that CPP DOT1L forms stable complexes with pEGFP-L1-E7, significantly enhancing cellular uptake in both cancerous and non-cancerous cell lines. Finally, results from immunizing mice with DOT1L/pcDNA-L1-E7 complexes revealed a robust cell-mediated immune response, characterized by a significant increase in Th1 cytokines (Interferon-gamma, Tumor necrosis factor-α) and Granzyme B compared to the pcDNA-L1-E7 vaccine alone. This comprehensive evaluation highlights CPP DOT1L as a promising delivery tool to overcome cellular barriers and improve DNA vaccine efficacy, and provides a strategic framework for developing future therapeutic HPV vaccines.
{"title":"Potential of DOT1L cell-penetrating peptide to enhance delivery of HPV multi-epitope DNA vaccine candidate: Insights from in silico, in vitro and in vivo studies","authors":"Farkhondeh Pooresmaeil , Azam Bolhassani , Arshad Hosseini , Behnam Hasannejad-asl , Parisa Moradi Pordanjani , Mehri Nazeri","doi":"10.1016/j.jddst.2026.108008","DOIUrl":"10.1016/j.jddst.2026.108008","url":null,"abstract":"<div><div>While Food and Drug Administration (FDA)-approved prophylactic human papillomavirus (HPV) vaccines are available, their inability to treat existing infections highlights the urgent need for therapeutic vaccines targeting pre-existing infections. DNA-based vaccines represent a promising solution; however, their weak immunogenicity necessitates an effective delivery system. Cell-penetrating peptides (CPPs) are powerful vectors for DNA delivery, offering several advantages over viral vectors. This study examines the potential of the CPP DOT1L to enhance the delivery and efficacy of an HPV L1-E7 multi-epitope DNA vaccine using integrated <em>in silico</em>, <em>in vitro</em>, and <em>in vivo</em> approaches. In <em>silico</em> studies, molecular docking revealed that DOT1L binds to the DNA duplex via interactions between its Arginine and Lysine residues and the DNA major groove. The CPP DOT1L also has a strong affinity for the membrane due to these positively charged residues. Molecular Dynamics simulations indicated that DOT1L can efficiently penetrate the membrane, while the DNA duplex has limited interfacial interactions. <em>In vitro</em> experiments confirmed that CPP DOT1L forms stable complexes with pEGFP-L1-E7, significantly enhancing cellular uptake in both cancerous and non-cancerous cell lines. Finally, results from immunizing mice with DOT1L/pcDNA-L1-E7 complexes revealed a robust cell-mediated immune response, characterized by a significant increase in Th1 cytokines (Interferon-gamma, Tumor necrosis factor-α) and Granzyme B compared to the pcDNA-L1-E7 vaccine alone. This comprehensive evaluation highlights CPP DOT1L as a promising delivery tool to overcome cellular barriers and improve DNA vaccine efficacy, and provides a strategic framework for developing future therapeutic HPV vaccines.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108008"},"PeriodicalIF":4.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074419","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}
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