Pub Date : 2026-01-27DOI: 10.1016/j.jddst.2026.108066
Ayşegül Yıldız, N. Başaran Mutlu-Ağardan, Füsun Acartürk
Silk fibroin is a biopolymer of natural origin which could be obtained simply and affordably from silkworm cocoon using various extraction agents. It has many advantages such as biocompatibility, biodegradability, low immunogenicity, low toxicity, high water vapor permeability, high mechanical resistance, etc. Owing to those properties, it attracts attention in many fields such as tissue engineering, cancer treatment, enzyme immobilization, wound healing, and the treatment of inflammatory bowel disease. This review outlines the properties and production methods of silk fibroin, and comprehensively summarizes its biomedical applications, including tissue engineering (bone, cartilage, musculoskeletal, skin, eardrum, dental, tracheal, tendon and ligament, cardiac, ocular, hepatic, spinal cord and intervertebral disc), artificial skin substitutes, cancer therapy, wound healing, inflammatory bowel disease and drug delivery systems.
{"title":"Silk fibroin: features, production methods and medical applications","authors":"Ayşegül Yıldız, N. Başaran Mutlu-Ağardan, Füsun Acartürk","doi":"10.1016/j.jddst.2026.108066","DOIUrl":"10.1016/j.jddst.2026.108066","url":null,"abstract":"<div><div>Silk fibroin is a biopolymer of natural origin which could be obtained simply and affordably from silkworm cocoon using various extraction agents. It has many advantages such as biocompatibility, biodegradability, low immunogenicity, low toxicity, high water vapor permeability, high mechanical resistance, etc. Owing to those properties, it attracts attention in many fields such as tissue engineering, cancer treatment, enzyme immobilization, wound healing, and the treatment of inflammatory bowel disease. This review outlines the properties and production methods of silk fibroin, and comprehensively summarizes its biomedical applications, including tissue engineering (bone, cartilage, musculoskeletal, skin, eardrum, dental, tracheal, tendon and ligament, cardiac, ocular, hepatic, spinal cord and intervertebral disc), artificial skin substitutes, cancer therapy, wound healing, inflammatory bowel disease and drug delivery systems.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"118 ","pages":"Article 108066"},"PeriodicalIF":4.9,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172261","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}
Pub Date : 2026-01-23DOI: 10.1016/j.jddst.2026.108036
Angela Cerulo, Nicola Antonio Di Spirito, Nino Grizzuti, Rossana Pasquino
During the last three decades, the design of refined nanosized drug delivery systems employed peculiar temperature-responsive synthetic copolymers, Pluronics, capable to mimic biological systems. Biocompatibility and biodegradability, along with the possibility of opportunely tailoring the desired features of these macromolecules, can be exploited to develop carriers able to improve the solubility and the bioavailability of hydrophobic drugs. As passive agents, Pluronics have a high drug loading capacity in water and low immunogenicity, but they can also play a more active role by reacting to temperature changes. Within specific ranges of concentration, Pluronic aqueous solutions can be injected in liquid form and become soft solids at body temperature, allowing to modulate the drug release. The presence of additives can modify the thermal response of Pluronic molecules in water, possibly sensitizing the system to other stimuli (e.g., pH). In this work, the addition of hydrophobic Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) – ibuprofen (IBU), ibuprofen sodium salt (IBUNa), diclofenac potassium (DK) – in a 45 wt% Pluronic F68 aqueous solution was investigated by rheology, Differential Scanning Calorimetry (DSC), surface tension and wettability measurements. Pluronic F68 significantly increased the solubility of the drug in water. The thermo-reversible, self-assembling process was followed and phase transitions were identified through rheological oscillatory and steady measurements and calorimetric evaluations at different drug concentrations and temperatures. The effect of pH was also discussed by varying the drug type and its concentration. Lastly, empirical phase diagrams for the drug/Pluronic aqueous solutions were built.
{"title":"Amphiphile-drug interplay: Enhanced solubility and drug-tailored self-assembly for delivery applications","authors":"Angela Cerulo, Nicola Antonio Di Spirito, Nino Grizzuti, Rossana Pasquino","doi":"10.1016/j.jddst.2026.108036","DOIUrl":"10.1016/j.jddst.2026.108036","url":null,"abstract":"<div><div>During the last three decades, the design of refined nanosized drug delivery systems employed peculiar temperature-responsive synthetic copolymers, Pluronics, capable to mimic biological systems. Biocompatibility and biodegradability, along with the possibility of opportunely tailoring the desired features of these macromolecules, can be exploited to develop carriers able to improve the solubility and the bioavailability of hydrophobic drugs. As passive agents, Pluronics have a high drug loading capacity in water and low immunogenicity, but they can also play a more active role by reacting to temperature changes. Within specific ranges of concentration, Pluronic aqueous solutions can be injected in liquid form and become soft solids at body temperature, allowing to modulate the drug release. The presence of additives can modify the thermal response of Pluronic molecules in water, possibly sensitizing the system to other stimuli (e.g., pH). In this work, the addition of hydrophobic Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) – ibuprofen (IBU), ibuprofen sodium salt (IBUNa), diclofenac potassium (DK) – in a 45 wt% Pluronic F68 aqueous solution was investigated by rheology, Differential Scanning Calorimetry (DSC), surface tension and wettability measurements. Pluronic F68 significantly increased the solubility of the drug in water. The thermo-reversible, self-assembling process was followed and phase transitions were identified through rheological oscillatory and steady measurements and calorimetric evaluations at different drug concentrations and temperatures. The effect of pH was also discussed by varying the drug type and its concentration. Lastly, empirical phase diagrams for the drug/Pluronic aqueous solutions were built.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108036"},"PeriodicalIF":4.9,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074405","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 : 2026-01-22DOI: 10.1016/j.jddst.2026.108050
Júlia Elizabeth Pigatto Stringhi, Bianca Costa Bernardo Port, Thiago Caon
Although polymeric microneedles (MNs) have gained attention for vaccination and deposition of large molecules into the skin, insufficient mechanical properties have limited the number of devices reaching the market. Fracture of needles resulting in premature drug release and inability to pierce the skin have been the most common problems. Given that MNs represent an emerging technology, the lack of standardized formulation characterization protocols coupled with the current gaps in the regulatory framework can lead to the market introduction of MNs with questionable quality. The selection of inappropriate membrane models for MN penetration assays, skin regions differing from the intended application site, problems in tissue processing and inadequate storage conditions may be the cause of mechanical failures, which were discussed in detail in this study. Some disease states can also make the skin more rigid or more elastic, demanding adjustments in MN design (composition, dimensions). In the first situation, the mechanical properties of MNs should be improved and then approaches such as polymer combinations instead of a single polymer; the addition of sugars, nano/microparticles and polymer cross-linking reactions could be considered. When a skin is more elastic, adjustments in MN dimensions (needle length/tip) are recommended. Different from other studies that have analyzed approaches for improving the mechanical properties of MNs, this study brings further data on conditions able to affect the skin viscoelasticity/structure, which would impact MN performance. Therefore, more rational devices could be designed, reducing the rate of refusal of products in the commercialization phase as well as clinical complications.
{"title":"Insights into conditions affecting the skin viscoelasticity for the design of polymeric microneedles with optimal mechanical properties","authors":"Júlia Elizabeth Pigatto Stringhi, Bianca Costa Bernardo Port, Thiago Caon","doi":"10.1016/j.jddst.2026.108050","DOIUrl":"10.1016/j.jddst.2026.108050","url":null,"abstract":"<div><div>Although polymeric microneedles (MNs) have gained attention for vaccination and deposition of large molecules into the skin, insufficient mechanical properties have limited the number of devices reaching the market. Fracture of needles resulting in premature drug release and inability to pierce the skin have been the most common problems. Given that MNs represent an emerging technology, the lack of standardized formulation characterization protocols coupled with the current gaps in the regulatory framework can lead to the market introduction of MNs with questionable quality. The selection of inappropriate membrane models for MN penetration assays, skin regions differing from the intended application site, problems in tissue processing and inadequate storage conditions may be the cause of mechanical failures, which were discussed in detail in this study. Some disease states can also make the skin more rigid or more elastic, demanding adjustments in MN design (composition, dimensions). In the first situation, the mechanical properties of MNs should be improved and then approaches such as polymer combinations instead of a single polymer; the addition of sugars, nano/microparticles and polymer cross-linking reactions could be considered. When a skin is more elastic, adjustments in MN dimensions (needle length/tip) are recommended. Different from other studies that have analyzed approaches for improving the mechanical properties of MNs, this study brings further data on conditions able to affect the skin viscoelasticity/structure, which would impact MN performance. Therefore, more rational devices could be designed, reducing the rate of refusal of products in the commercialization phase as well as clinical complications.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108050"},"PeriodicalIF":4.9,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074483","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}
Therapeutic proteins often exhibit rapid clearance from circulation, necessitating frequent dosing and impairing patient adherence. Here, we aimed to develop an albumin-binding VHH (variable domain of heavy chain-only antibody) to extend protein half-life via FcRn(neonatal Fc receptor)-mediated recycling, using follicle-stimulating hormone (FSH) as a model. Anti-HSA VHHs were isolated from a naïve alpaca phage library (with cross-reactivity to cynomolgus serum albumin, Cyno-SA) and characterized via surface plasmon resonance (SPR) for binding affinity. AlphaFold3-predicted VHH-HSA complex structures were validated by alanine-scanning mutagenesis. Pharmacokinetics (PK) were assessed in hFcRn-transgenic mice and cynomolgus monkeys, and translational utility was tested using the lead VHH-scFSH fusion (FSH-m7). The lead VHH bound human/Cyno-SA with high affinity, extending systemic exposure and reducing clearance in monkeys. FSH-m7 retained bioactivity, showed prolonged half-life (vs. wild-type FSH) with lower Cmax in humanized mice, and induced dose-dependent ovarian growth and higher estradiol in juvenile rats at equivalent molar doses. This HSA-binding VHH enables robust cross-species half-life extension of protein therapeutics while preserving activity, providing a generalizable platform for engineering albumin-binding biologics to support less frequent dosing and improved adherence.
{"title":"Engineering and translational evaluation of A Novel Albumin-binding variable domain of heavy chain-only antibody for half-life extension","authors":"Chengkai Yin , Tianyan Liu, Dan Yu, Yuanyuan Yan, Xuelei Pi, Panpan Sun, Hongna Chen, Jiarui Yang, Zhenzhong Wang, Zhihang Liu","doi":"10.1016/j.jddst.2026.108044","DOIUrl":"10.1016/j.jddst.2026.108044","url":null,"abstract":"<div><div>Therapeutic proteins often exhibit rapid clearance from circulation, necessitating frequent dosing and impairing patient adherence. Here, we aimed to develop an albumin-binding VHH (variable domain of heavy chain-only antibody) to extend protein half-life via FcRn(neonatal Fc receptor)-mediated recycling, using follicle-stimulating hormone (FSH) as a model. Anti-HSA VHHs were isolated from a naïve alpaca phage library (with cross-reactivity to cynomolgus serum albumin, Cyno-SA) and characterized via surface plasmon resonance (SPR) for binding affinity. AlphaFold3-predicted VHH-HSA complex structures were validated by alanine-scanning mutagenesis. Pharmacokinetics (PK) were assessed in hFcRn-transgenic mice and cynomolgus monkeys, and translational utility was tested using the lead VHH-scFSH fusion (FSH-m7). The lead VHH bound human/Cyno-SA with high affinity, extending systemic exposure and reducing clearance in monkeys. FSH-m7 retained bioactivity, showed prolonged half-life (vs. wild-type FSH) with lower Cmax in humanized mice, and induced dose-dependent ovarian growth and higher estradiol in juvenile rats at equivalent molar doses. This HSA-binding VHH enables robust cross-species half-life extension of protein therapeutics while preserving activity, providing a generalizable platform for engineering albumin-binding biologics to support less frequent dosing and improved adherence.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 108044"},"PeriodicalIF":4.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035412","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号