Dengue virus (DENV) infection remains a major global health threat, with no specific antiviral treatment currently approved. Monoclonal antibody (mAb) therapy represents a promising strategy for viral inhibition; however, conventional antibodies are largely restricted to extracellular compartments and lack access to intracellular viral replication sites. In this study, we encapsulated a cross-reactive mAb targeting the DENV envelope protein (m513) into poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles to facilitate intracellular delivery. When applied to immortalized hepatocyte-like cells (imHCs), the formulation demonstrated efficient cellular uptake, low cytotoxicity, and significantly reduced intracellular viral RNA and protein levels. The resulting formulation consisted of mAb-loaded PEG-PLGA nanoparticles (∼100 nm in diameter) with spherical morphology and an encapsulation efficiency of approximately 50%. Furthermore, nanoparticle treatment significantly reduced hepatocyte apoptosis in infected cells. Collectively, these findings demonstrate that nanoparticle-mediated intracellular antibody delivery can overcome a key limitation of conventional antibody therapy and represents a mechanistically distinct antiviral strategy for DENV and other intracellular viral infections.
{"title":"Intracellular delivery of anti-dengue envelope monoclonal antibodies via PEG-PLGA nanoparticles suppresses viral replication and attenuates hepatocyte apoptosis","authors":"Nutthanicha Intrarakasem , Sorawee Kaewkarn , Phitchapha Proykhunthod , Adisak Songjaeng , Panisadee Avirutnun , Tanapan Prommool , Chunya Puttikhunt , Anupong Makeudom , Atthapan Morchang , Xiaohe Tian , Giuseppe Battaglia , Nisa Patikarnmonthon , Romchat Kraivong","doi":"10.1016/j.jddst.2026.108086","DOIUrl":"10.1016/j.jddst.2026.108086","url":null,"abstract":"<div><div>Dengue virus (DENV) infection remains a major global health threat, with no specific antiviral treatment currently approved. Monoclonal antibody (mAb) therapy represents a promising strategy for viral inhibition; however, conventional antibodies are largely restricted to extracellular compartments and lack access to intracellular viral replication sites. In this study, we encapsulated a cross-reactive mAb targeting the DENV envelope protein (m513) into poly(ethylene glycol)-<em>block</em>-poly(lactide-<em>co</em>-glycolide) (PEG-PLGA) nanoparticles to facilitate intracellular delivery. When applied to immortalized hepatocyte-like cells (imHCs), the formulation demonstrated efficient cellular uptake, low cytotoxicity, and significantly reduced intracellular viral RNA and protein levels. The resulting formulation consisted of mAb-loaded PEG-PLGA nanoparticles (∼100 nm in diameter) with spherical morphology and an encapsulation efficiency of approximately 50%. Furthermore, nanoparticle treatment significantly reduced hepatocyte apoptosis in infected cells. Collectively, these findings demonstrate that nanoparticle-mediated intracellular antibody delivery can overcome a key limitation of conventional antibody therapy and represents a mechanistically distinct antiviral strategy for DENV and other intracellular viral infections.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"118 ","pages":"Article 108086"},"PeriodicalIF":4.9,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102469","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}
The therapeutic potential of Tamoxifen, a frontline drug in the treatment of breast cancer is limited by its poor aqueous solubility and limited bioavailability resulting in sub-optimal therapeutic benefits. Herein, we report a novel coamorphous system of tamoxifen with rational-driven selected coformer curcumin demonstrating dual-function role, wherein stabilizing tamoxifen in its amorphous state with boosted anticancer activity. The coamorphous phase was extensively characterized using PXRD, modulated DSC, and IR spectroscopy and was also found to be stable as revealed by accelerated and long term stability studies. The modified form showed significant improvement in the solubility and dissolution compared to the pristine drug. Ex vivo gut sac permeability revealed greater intestinal permeability while in vivo pharmacokinetic profile in female SD rats demonstrated improved oral bioavailability with prolonged Tmax showing extended systemic drug exposure. Remarkably, excellent synergism was noted between the components, wherein the bioavailability of tamoxifen was enhanced by curcumin and vice versa. In vitro pharmacological assays using MCF-7 breast cancer cells showed enhanced ROS generation, mitochondrial membrane disintegration, and flow cytometry analysis revealed early onset of apoptosis and cell cycle arrest at G0/G1 phase. Western blotting analysis further confirmed modulation of key apoptotis related proteins, Bcl-2, Bax, and Caspase-3 revealing the pro-apoptotic activity of CAM system. The modified formulation was found to be superior in suppressing cell migration and proliferation of the cancer cells. In vitro biocompatibility assays in non cancerous cells and haemolytic assays revealed CAM has good tolerability and safety profile. These findings prove the potential of the modified coamorphous form as a promising strategy for developing synergistically effective formulation of tamoxifen, offering superior therapeutic outcomes compared to the pristine drug in the treatment of breast cancer therapy.
{"title":"Coamorphous system of tamoxifen and curcumin: Tailored release, synergism and enhanced pharmacological outcomes to combat breast cancer","authors":"Nagamalli Naga Sidhartha , Soumyajit Dey , Shrilekha Chilvery , Anamika Sharma , Chandraiah Godugu , Amol G. Dikundwar","doi":"10.1016/j.jddst.2026.108076","DOIUrl":"10.1016/j.jddst.2026.108076","url":null,"abstract":"<div><div>The therapeutic potential of Tamoxifen, a frontline drug in the treatment of breast cancer is limited by its poor aqueous solubility and limited bioavailability resulting in sub-optimal therapeutic benefits. Herein, we report a novel coamorphous system of tamoxifen with rational-driven selected coformer curcumin demonstrating dual-function role, wherein stabilizing tamoxifen in its amorphous state with boosted anticancer activity. The coamorphous phase was extensively characterized using PXRD, modulated DSC, and IR spectroscopy and was also found to be stable as revealed by accelerated and long term stability studies. The modified form showed significant improvement in the solubility and dissolution compared to the pristine drug. <em>Ex vivo</em> gut sac permeability revealed greater intestinal permeability while <em>in vivo</em> pharmacokinetic profile in female SD rats demonstrated improved oral bioavailability with prolonged T<sub>max</sub> showing extended systemic drug exposure. Remarkably, excellent synergism was noted between the components, wherein the bioavailability of tamoxifen was enhanced by curcumin and vice versa. <em>In vitro</em> pharmacological assays using MCF-7 breast cancer cells showed enhanced ROS generation, mitochondrial membrane disintegration, and flow cytometry analysis revealed early onset of apoptosis and cell cycle arrest at G0/G1 phase. Western blotting analysis further confirmed modulation of key apoptotis related proteins, Bcl-2, Bax, and Caspase-3 revealing the pro-apoptotic activity of CAM system. The modified formulation was found to be superior in suppressing cell migration and proliferation of the cancer cells. <em>In vitro</em> biocompatibility assays in non cancerous cells and haemolytic assays revealed CAM has good tolerability and safety profile. These findings prove the potential of the modified coamorphous form as a promising strategy for developing synergistically effective formulation of tamoxifen, offering superior therapeutic outcomes compared to the pristine drug in the treatment of breast cancer therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"118 ","pages":"Article 108076"},"PeriodicalIF":4.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102470","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}
The development of localized and sustained drug delivery systems remains a critical challenge in glioblastoma therapy due to rapid drug clearance and systemic toxicity. In this study, a smart hybrid delivery platform was engineered by integrating amino-functionalized iron-based metal–organic frameworks (NH2-MIL-88B(Fe)) into dual-crosslinked sodium alginate/polyvinyl alcohol hydrogel thin films for controlled 5-fluorouracil (5-FU) delivery. The resulting composite films exhibited high hydrophilicity and structural stability, supporting efficient drug accommodation and diffusion regulation. Comprehensive physicochemical characterization confirmed uniform incorporation of the porous framework within the polymeric network, yielding a mesoporous architecture with an average pore size of ∼2.75 nm and a specific surface area of ∼17.322 m2/g. The system achieved a high encapsulation efficiency (up to 92.18 %) and demonstrated sustained, non-burst drug release, reaching ∼78.4 % cumulative release over 120 h under physiological conditions, with kinetics consistent with diffusion-dominated non-Fickian transport. In vitro cytotoxicity studies using U-87 glioblastoma cells revealed enhanced anticancer activity with moderated toxicity relative to burst-release free 5-FU, indicating effective therapeutic performance with improved biocompatibility. These findings establish the MOF–hydrogel hybrid thin-film system as a promising localized delivery platform for glioblastoma treatment.
{"title":"Smart MOF-integrated biopolymeric hydrogel systems as a novel strategy for sustained anticancer drug delivery","authors":"Zubda Ilyas , Aneela Javed , Waheed Miran , Muhammad Bilal Khan Niazi , Usman Liaqat","doi":"10.1016/j.jddst.2026.108049","DOIUrl":"10.1016/j.jddst.2026.108049","url":null,"abstract":"<div><div>The development of localized and sustained drug delivery systems remains a critical challenge in glioblastoma therapy due to rapid drug clearance and systemic toxicity. In this study, a smart hybrid delivery platform was engineered by integrating amino-functionalized iron-based metal–organic frameworks (NH<sub>2</sub>-MIL-88B(Fe)) into dual-crosslinked sodium alginate/polyvinyl alcohol hydrogel thin films for controlled 5-fluorouracil (5-FU) delivery. The resulting composite films exhibited high hydrophilicity and structural stability, supporting efficient drug accommodation and diffusion regulation. Comprehensive physicochemical characterization confirmed uniform incorporation of the porous framework within the polymeric network, yielding a mesoporous architecture with an average pore size of ∼2.75 nm and a specific surface area of ∼17.322 m<sup>2</sup>/g. The system achieved a high encapsulation efficiency (up to 92.18 %) and demonstrated sustained, non-burst drug release, reaching ∼78.4 % cumulative release over 120 h under physiological conditions, with kinetics consistent with diffusion-dominated non-Fickian transport. In vitro cytotoxicity studies using U-87 glioblastoma cells revealed enhanced anticancer activity with moderated toxicity relative to burst-release free 5-FU, indicating effective therapeutic performance with improved biocompatibility. These findings establish the MOF–hydrogel hybrid thin-film system as a promising localized delivery platform for glioblastoma treatment.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"118 ","pages":"Article 108049"},"PeriodicalIF":4.9,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102468","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}
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited therapies. Histone deacetylase inhibitors have emerged as promising antifibrotic agents by modulating fibrogenic pathways. Localized pulmonary delivery is particularly important to maximize lung exposure while minimizing systemic toxicity. Dry powder inhalers offer advantages, including rapid delivery, portability, and patient adherence. In this study, an inhalable dry powder formulation of J27644, a selective HDAC6/HDAC8 inhibitor, was developed using three-fluid nozzle spray drying (3FNSD) with zein as a hydrophobic coating excipient and lactose as a bulking agent. Zein dissolved in ethanol was delivered through the middle channel of the nozzle, while J27644 and lactose co-dissolved in an ethanol-water cosolvent were introduced through the innermost channel. A Box-Behnken design was applied to optimize spray gas flow (600-1600 L/h), inlet temperature (50-150 °C), feeding rate (2-6 mL/min), and zein content (5-30 %). Zein content was identified as the dominant factor influencing surface coverage, while spray gas, inlet temperature, and zein content contributed to recrystallization resistance at 25 °C/40 % relative humidity (RH). The optimized 3FNSD formulation achieved a zein surface coverage of 79.6 % and negligible mass loss (0 %) at 25 °C/40 % RH, closely matching model predictions (82.6 % and 0 %). This formulation also exhibited an amorphous, raisin-like morphology with a D50 of 1.48 ± 0.00 μm. In vitro dispersion testing showed superior aerosolization for 3FNSD, with the highest emitted dose (177.0 ± 19.5 μg from a 300-μg load), fine particle dose (151.1 ± 18.0 μg), and the lowest mass median aerodynamic diameter (1.61 ± 0.02 μm), compared with controls prepared by two-fluid nozzle spray drying (2FNSD) and 2FNSD without zein. Dissolution testing demonstrated >70 % release within 60 min for all formulations. Difference factor (f1) analysis confirmed comparable dissolution between 2FNSD and 3FNSD (f1 = 8.95), whereas the zein-free formulation released faster and deviated from 3FNSD (f1 = 19.6). These findings demonstrate the feasibility of 3FNSD to produce zein-coated lactose-J27644 powders with enhanced moisture stability, favorable aerosolization, and preserved dissolution, supporting the application of zein and the three-fluid nozzle in spray-dried powder formulations for inhalation.
{"title":"Development and optimization of a zein-coated inhalable HDAC inhibitor formulation as a potential treatment for idiopathic pulmonary fibrosis via three-fluid nozzle spray drying","authors":"Wei-Ren Ke, Sheng-Chieh Hsiao, Meng-Tsung Cheng, Chao-Wu Yu","doi":"10.1016/j.jddst.2026.108065","DOIUrl":"10.1016/j.jddst.2026.108065","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited therapies. Histone deacetylase inhibitors have emerged as promising antifibrotic agents by modulating fibrogenic pathways. Localized pulmonary delivery is particularly important to maximize lung exposure while minimizing systemic toxicity. Dry powder inhalers offer advantages, including rapid delivery, portability, and patient adherence. In this study, an inhalable dry powder formulation of J27644, a selective HDAC6/HDAC8 inhibitor, was developed using three-fluid nozzle spray drying (3FNSD) with zein as a hydrophobic coating excipient and lactose as a bulking agent. Zein dissolved in ethanol was delivered through the middle channel of the nozzle, while J27644 and lactose co-dissolved in an ethanol-water cosolvent were introduced through the innermost channel. A Box-Behnken design was applied to optimize spray gas flow (600-1600 L/h), inlet temperature (50-150 °C), feeding rate (2-6 mL/min), and zein content (5-30 %). Zein content was identified as the dominant factor influencing surface coverage, while spray gas, inlet temperature, and zein content contributed to recrystallization resistance at 25 °C/40 % relative humidity (RH). The optimized 3FNSD formulation achieved a zein surface coverage of 79.6 % and negligible mass loss (0 %) at 25 °C/40 % RH, closely matching model predictions (82.6 % and 0 %). This formulation also exhibited an amorphous, raisin-like morphology with a D50 of 1.48 ± 0.00 μm. <em>In vitro</em> dispersion testing showed superior aerosolization for 3FNSD, with the highest emitted dose (177.0 ± 19.5 μg from a 300-μg load), fine particle dose (151.1 ± 18.0 μg), and the lowest mass median aerodynamic diameter (1.61 ± 0.02 μm), compared with controls prepared by two-fluid nozzle spray drying (2FNSD) and 2FNSD without zein. Dissolution testing demonstrated >70 % release within 60 min for all formulations. Difference factor (f<sub>1</sub>) analysis confirmed comparable dissolution between 2FNSD and 3FNSD (f<sub>1</sub> = 8.95), whereas the zein-free formulation released faster and deviated from 3FNSD (f<sub>1</sub> = 19.6). These findings demonstrate the feasibility of 3FNSD to produce zein-coated lactose-J27644 powders with enhanced moisture stability, favorable aerosolization, and preserved dissolution, supporting the application of zein and the three-fluid nozzle in spray-dried powder formulations for inhalation.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108065"},"PeriodicalIF":4.9,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073702","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 : 2026-01-26DOI: 10.1016/j.jddst.2026.108063
Huanfan He , Chengke Zhao , Jiayu Li, Xiaojing Pei, Hong Meng, Ze Zhang
The expression of the Cluster of Differentiation 44 (CD44) receptor on the surface of keratinocytes provides a programmable target for localised precision drug delivery in the skin. The development of hyaluronic acid surface-modified ceramide cationic nanoemulsions (HA-CER-CNE) was based on electrostatic self-assembly between anionic hyaluronic acid (HA) and cationic ceramide nanoemulsions (CER-CNE). This carrier combines three functions: receptor-ligand-mediated endocytosis, high drug-loading capacity, and barrier repair. The subject under discussion here is an advancement on traditional ceramide formulations. The latter are limited by short skin retention times, low bioavailability, and unclear target specificity. The study found that HA-CER-CNE was significantly more endocytosed by HaCaT cells than CER-CNE. This was due to the specific binding of HA to the CD44 receptor, which was confirmed by confocal laser scanning microscopy (CLSM). An in vitro skin retention test demonstrated a 1.17-fold and 2.29-fold increase in skin retention of ceramide NP with HA-CER-CNE in comparison with CER-CNE and CER-suspension at 24 h. Furthermore, a cell scratch assay was employed to ascertain that HA-CER-CNE can further improve barrier damage. The cell migration rate of the HA-CER-CNE sample was 76.81 %, in comparison to 58.59 % for the CER-CNE sample. This indicates an enhancement of cell migration of 31.10 % in the former sample. The efficacy evaluation of HA-CER-CNE demonstrated that, incompared to CER-CNE and CER-suspension, HA-CER-CNE enhanced skin hydration by 1.62-fold and 4.13-fold, respectively, and reduced transdermal water loss (TEWL) by 1.75-fold and 4.23-fold, respectively, over a period of seven days. The findings demonstrate that HA-CER-CNE achieves precise delivery and retention of ceramides via a CD44-targeting strategy, exhibiting dual properties as both a drug carrier and bioactive agent.
{"title":"Hyaluronic acid-modified cationic nanoemulsion prepared by electrostatic self-assembly for improved specific targeting of keratinocytes and enhanced barrier repair efficacy","authors":"Huanfan He , Chengke Zhao , Jiayu Li, Xiaojing Pei, Hong Meng, Ze Zhang","doi":"10.1016/j.jddst.2026.108063","DOIUrl":"10.1016/j.jddst.2026.108063","url":null,"abstract":"<div><div>The expression of the Cluster of Differentiation 44 (CD44) receptor on the surface of keratinocytes provides a programmable target for localised precision drug delivery in the skin<strong>.</strong> The development of hyaluronic acid surface-modified ceramide cationic nanoemulsions (HA-CER-CNE) was based on electrostatic self-assembly between anionic hyaluronic acid (HA) and cationic ceramide nanoemulsions (CER-CNE). This carrier combines three functions: receptor-ligand-mediated endocytosis, high drug-loading capacity, and barrier repair. The subject under discussion here is an advancement on traditional ceramide formulations. The latter are limited by short skin retention times, low bioavailability, and unclear target specificity. The study found that HA-CER-CNE was significantly more endocytosed by HaCaT cells than CER-CNE. This was due to the specific binding of HA to the CD44 receptor, which was confirmed by confocal laser scanning microscopy (CLSM). An in vitro skin retention test demonstrated a 1.17-fold and 2.29-fold increase in skin retention of ceramide NP with HA-CER-CNE in comparison with CER-CNE and CER-suspension at 24 h. Furthermore, a cell scratch assay was employed to ascertain that HA-CER-CNE can further improve barrier damage. The cell migration rate of the HA-CER-CNE sample was 76.81 %, in comparison to 58.59 % for the CER-CNE sample. This indicates an enhancement of cell migration of 31.10 % in the former sample. The efficacy evaluation of HA-CER-CNE demonstrated that, incompared to CER-CNE and CER-suspension, HA-CER-CNE enhanced skin hydration by 1.62-fold and 4.13-fold, respectively, and reduced transdermal water loss (TEWL) by 1.75-fold and 4.23-fold, respectively, over a period of seven days. The findings demonstrate that HA-CER-CNE achieves precise delivery and retention of ceramides via a CD44-targeting strategy, exhibiting dual properties as both a drug carrier and bioactive agent.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108063"},"PeriodicalIF":4.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073703","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 : 2026-01-25DOI: 10.1016/j.jddst.2026.108058
Majid Ghaedi , Jaleh Varshosaz , Mohammad Rabbani , Amir Mohammadsharifi Renani
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 in vitro 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 vs. 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. In vivo 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.
{"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":"2026-01-25","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}
Pub 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":"2026-01-25","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}
Periodontitis is a chronic inflammatory disease driven by biofilm-associated bacteria. Due to the limitations of conventional antimicrobials, this study evaluated the synergistic antibacterial and antibiofilm activities of alpha-mangostin extract (M) and citronella oil (C) against periodontal pathogens and developed lipid-based nanocarriers for local delivery in periodontal therapy. M and C were formulated into lipid-based nanocarriers, including nanoemulsions (NEs) and nanoemulgels (NEGs) to enhance their physicochemical properties. The formulations were evaluated for particle size, viscosity, drug release, antibiofilm activity, and cytotoxicity on human gingival fibroblasts (HGFs). The combination of M and C demonstrated a synergistic effect against Porphyromonas gingivalis (FICI ≤0.5). NEs and NEGs were successfully prepared for M and C loading; however, NEGs exhibited superior physical properties, including enhanced stability, good syringeability, acceptable viscosity, and controlled drug release, with MC-loaded NEGs showing a mean particle size of 307.6 ± 17.0 nm. Crucially, MC-loaded NEGs showed potent antibiofilm activity, achieving greater than 90 % inhibition of periodontal pathogen biofilms, comparable to 0.12 % chlorhexidine. Furthermore, the formulation demonstrated excellent biocompatibility, with HGF cell viability remaining above 85 % at concentrations up to 1000 μg/mL. These results suggest that MC-loaded NEGs are a promising and safe antimicrobial agent for managing periodontal disease.
{"title":"Development of alpha-mangostin extract and citronella oil-loaded lipid-based nanocarriers for use as an antimicrobial agent in the treatment of periodontitis","authors":"Wipada Samprasit , Ruchadaporn Kaomongkolgit , Benchawan Chamsai , Praneet Opanasopit , Ichaya Yiamwattana , Weeraya Tantanapornkul , Kusuma Jamdee , Suttimas Yuakyong","doi":"10.1016/j.jddst.2026.108056","DOIUrl":"10.1016/j.jddst.2026.108056","url":null,"abstract":"<div><div>Periodontitis is a chronic inflammatory disease driven by biofilm-associated bacteria. Due to the limitations of conventional antimicrobials, this study evaluated the synergistic antibacterial and antibiofilm activities of alpha-mangostin extract (M) and citronella oil (C) against periodontal pathogens and developed lipid-based nanocarriers for local delivery in periodontal therapy. M and C were formulated into lipid-based nanocarriers, including nanoemulsions (NEs) and nanoemulgels (NEGs) to enhance their physicochemical properties. The formulations were evaluated for particle size, viscosity, drug release, antibiofilm activity, and cytotoxicity on human gingival fibroblasts (HGFs). The combination of M and C demonstrated a synergistic effect against <em>Porphyromonas gingivalis</em> (FICI ≤0.5). NEs and NEGs were successfully prepared for M and C loading; however, NEGs exhibited superior physical properties, including enhanced stability, good syringeability, acceptable viscosity, and controlled drug release, with MC-loaded NEGs showing a mean particle size of 307.6 ± 17.0 nm. Crucially, MC-loaded NEGs showed potent antibiofilm activity, achieving greater than 90 % inhibition of periodontal pathogen biofilms, comparable to 0.12 % chlorhexidine. Furthermore, the formulation demonstrated excellent biocompatibility, with HGF cell viability remaining above 85 % at concentrations up to 1000 μg/mL. These results suggest that MC-loaded NEGs are a promising and safe antimicrobial agent for managing periodontal disease.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108056"},"PeriodicalIF":4.9,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074417","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}
Natural particle-stabilized Pickering emulsions have become prospective delivery vehicles in transdermal drug delivery due to their eco-friendliness, biocompatibility and minimal skin irritation. Herein, the transdermal delivery performance of oil-in-water Pickering emulsions stabilized by pumpkin seed protein isolate (PSPI)/λ-carrageenan (λCG) was investigated. λCG was found to improve the behavior of PSPI particles at the oil/water interface by increasing surface charge density and interacting with PSPI, thus optimizing the emulsifying property of PSPI and enhancing its protection performance on active substances. In vitro skin permeation studies demonstrated that λCG significantly promoted the transdermal delivery efficiency of PSPI-stabilized Pickering emulsions. Specifically, the 2.0 % λCG group yielded a 118.18 % increase in cumulated α-bisabolol in stratum corneum layer, a 52.59 % increase in the cumulated amount in the viable epidermis and dermis layer, 130.37 % increase in the subcutaneous layer, and an overall 96.23 % increase in total cumulated skin permeation compared to the pure PSPI group. Attenuated total reflection Fourier transform infrared spectroscopy further demonstrated that λCG modulated the lipid structure of porcine stratum corneum, contributing to its permeation enhancement mechanism. The formulation proposed in this study may serve as a promising drug carrier system in the field of transdermal administration.
{"title":"Pickering emulsions stabilized by pumpkin seed protein isolate/λ-carrageenan and their transdermal delivery performance","authors":"Danni Yan, Yining Xi, Xiangyun Cheng, Yihan Guo, Yunxing Li, Cheng Yang, Yajuan Sun","doi":"10.1016/j.jddst.2026.108057","DOIUrl":"10.1016/j.jddst.2026.108057","url":null,"abstract":"<div><div>Natural particle-stabilized Pickering emulsions have become prospective delivery vehicles in transdermal drug delivery due to their eco-friendliness, biocompatibility and minimal skin irritation. Herein, the transdermal delivery performance of oil-in-water Pickering emulsions stabilized by pumpkin seed protein isolate (PSPI)/λ-carrageenan (λCG) was investigated. λCG was found to improve the behavior of PSPI particles at the oil/water interface by increasing surface charge density and interacting with PSPI, thus optimizing the emulsifying property of PSPI and enhancing its protection performance on active substances. <em>In vitro</em> skin permeation studies demonstrated that λCG significantly promoted the transdermal delivery efficiency of PSPI-stabilized Pickering emulsions. Specifically, the 2.0 % λCG group yielded a 118.18 % increase in cumulated α-bisabolol in stratum corneum layer, a 52.59 % increase in the cumulated amount in the viable epidermis and dermis layer, 130.37 % increase in the subcutaneous layer, and an overall 96.23 % increase in total cumulated skin permeation compared to the pure PSPI group. Attenuated total reflection Fourier transform infrared spectroscopy further demonstrated that λCG modulated the lipid structure of porcine stratum corneum, contributing to its permeation enhancement mechanism. The formulation proposed in this study may serve as a promising drug carrier system in the field of transdermal administration.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108057"},"PeriodicalIF":4.9,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074421","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}
Synthetic zinc oxide nanoparticles (ZnO-NPs) produced by flame spray pyrolysis (FZnO-NPs) have been extensively studied for applications due to a one-step synthesis process, high purity, large external surface area, high noble metal dispersion, and scalability. Although these benefits have been illustrated, their potential in biomedical fields remains underexplored. To pursue the potential implication of using FZnO-NPs in lowering lipid levels, therefore, this study aimed to investigate the potential lipid-lowering effect in the transluminal gastrointestinal environment compared with commercially available (CZnO-NPs). Comparable in pore sizes, surface area, purity, morphology, charge, and stability of each type were determined. Changes in the physicochemical properties of cholesterol micelles induced by each ZnO-NPs were investigated along with the absorption of green fluorescent-25-[N-[(7-nitro-2-1,3-benzoxadiazol-4-yl)methyl]amino]-27-norcholesterol in the human colorectal adenocarcinoma (Caco-2) cell line and further validated with tritium-cholesterol micelle transport in rats. The findings demonstrated that FZnO-NPs had a smaller size and larger surface area compared to CZnO-NPs. In addition, FZnO-NPs significantly inhibited cholesterol absorption in Caco-2 cells, similar to the effect of the positive drug, ezetimibe, with a lesser potency. Consistently, FZnO-NPs were mechanistically more effective in aggregating and expanding cholesterol micelle size than CZnO-NPs. Nonetheless, both nanoparticle types exhibited high affinity for binding to bile acids. Correspondingly, FZnO-NPs markedly decreased cholesterol absorption, reflected by reducing cholesterol levels in plasma, jejunal, and hepatic tissues, comparable to ezetimibe's effect in rats. Thus, this study suggested that FZnO-NPs had promising therapeutic potential for lowering cholesterol levels by inhibiting cholesterol absorption, which could be an option for preventing hyperlipidemia.
{"title":"Inhibition of cholesterol absorption using flame-produced ZnO Nanoparticles: Potential applications in hyperlipidemia","authors":"Thanthakan Saithong , Kornwalai Tunkaew , Jakkapong Inchai , Pannita Holasut , Mameaseng Siriwalai , Chaikarn Liewhiran , Chutima S. Vaddhanaphuti","doi":"10.1016/j.jddst.2026.108054","DOIUrl":"10.1016/j.jddst.2026.108054","url":null,"abstract":"<div><div>Synthetic zinc oxide nanoparticles (ZnO-NPs) produced by flame spray pyrolysis (FZnO-NPs) have been extensively studied for applications due to a one-step synthesis process, high purity, large external surface area, high noble metal dispersion, and scalability. Although these benefits have been illustrated, their potential in biomedical fields remains underexplored. To pursue the potential implication of using FZnO-NPs in lowering lipid levels, therefore, this study aimed to investigate the potential lipid-lowering effect in the transluminal gastrointestinal environment compared with commercially available (CZnO-NPs). Comparable in pore sizes, surface area, purity, morphology, charge, and stability of each type were determined. Changes in the physicochemical properties of cholesterol micelles induced by each ZnO-NPs were investigated along with the absorption of green fluorescent-25-[N-[(7-nitro-2-1,3-benzoxadiazol-4-yl)methyl]amino]-27-norcholesterol in the human colorectal adenocarcinoma (Caco-2) cell line and further validated with tritium-cholesterol micelle transport in rats. The findings demonstrated that FZnO-NPs had a smaller size and larger surface area compared to CZnO-NPs. In addition, FZnO-NPs significantly inhibited cholesterol absorption in Caco-2 cells, similar to the effect of the positive drug, ezetimibe, with a lesser potency. Consistently, FZnO-NPs were mechanistically more effective in aggregating and expanding cholesterol micelle size than CZnO-NPs. Nonetheless, both nanoparticle types exhibited high affinity for binding to bile acids. Correspondingly, FZnO-NPs markedly decreased cholesterol absorption, reflected by reducing cholesterol levels in plasma, jejunal, and hepatic tissues, comparable to ezetimibe's effect in rats. Thus, this study suggested that FZnO-NPs had promising therapeutic potential for lowering cholesterol levels by inhibiting cholesterol absorption, which could be an option for preventing hyperlipidemia.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108054"},"PeriodicalIF":4.9,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074423","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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