Journal of Drug Delivery Science and Technology最新文献

{"title":"Harnessing nanoencapsulation for the repurposing of hydroquinidine against breast cancer","authors":"Turan Demircan ,&nbsp;Daela Milinkovic ,&nbsp;Esin Sakallı Çetin ,&nbsp;Ebrunur Aksu ,&nbsp;Oya Tagit","doi":"10.1016/j.jddst.2025.107098","DOIUrl":"10.1016/j.jddst.2025.107098","url":null,"abstract":"<div><div>Repurposing drugs beyond their original medical indications can facilitate cost- and time-effective drug development and a sustainable drug development process. Nanoencapsulation strategies can further expand the number of potentially suitable drug candidates for repurposing. In this study, we explored the anticancer efficacy of hydroquinidine (a class IA antiarrhythmic cinchona alkaloid drug) loaded into PLGA nanoparticles (HQ-NP) on breast cancer cells. The study compared HQ-NP to soluble hydroquinidine (HQ_sol) in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cell lines. Overall, nanoencapsulation resulted in more potent and selective toxicity in comparison to soluble drug. The mechanisms involved inducing apoptosis and oxidative stress, disruption of mitochondrial membrane potential, and suppression of cell proliferation. The enhanced potency of HQ-NP was consistent across multiple assays and on both cell lines, suggesting a broad applicability in different breast cancer subtypes. <em>In silico</em> analyses indicated the cancer-related pathways, such as PI3K-Akt and cAMP signaling, as potential targets of HQ, which is likely to be driven by the putative inhibition of voltage-gated ion channels as suggested by molecular docking studies. This research highlights the potential of HQ-NP as a novel, multi-modal anticancer agent for breast cancer treatment, warranting further investigation towards clinical application.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107098"},"PeriodicalIF":4.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose-modified PEG-PLA self-assembled nano-micelles optimize DOX enrichment, tissue penetration, and tumor suppression effects in pancreatic ductal adenocarcinoma","authors":"Zhijie Liang ,&nbsp;Jinzhuai Li ,&nbsp;Hai Huang ,&nbsp;Hongmian Jiang ,&nbsp;Lifeng Luo ,&nbsp;Shaorong Li ,&nbsp;Huali Huang ,&nbsp;Fangdi Hu","doi":"10.1016/j.jddst.2025.107073","DOIUrl":"10.1016/j.jddst.2025.107073","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) poses significant therapeutic challenges due to its unique tumor microenvironment, which is characterized by collapsed blood vessels and elevated intratumoral pressure, severely hindering drug penetration and distribution. Consequently, we synthesized glucose-modified PEG-PLA (polyethylene-polylactice acid) nanoparticles as a drug delivery system for doxorubicin (DOX). We successfully enhanced the permeability and targeting capability of the nanoparticles in pancreatic cancer cells using glycosylation modification, significantly increasing drug accumulation within the tumor microenvironment. Our study demonstrated excellent cellular uptake of the nanoparticles <em>in vitro</em> and their improved penetration in 3D tumor spheroid models. Additionally, <em>in vivo</em> experiments revealed a notable increase in nanoparticle accumulation at the tumor site, along with favorable drug release characteristics. Hence, glucose-modified PEG-PLA nanoparticles hold substantial potential for clinical application in PDAC treatment, effectively enhancing the therapeutic efficacy of chemotherapeutic agents.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107073"},"PeriodicalIF":4.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective topical delivery of astaxanthin via optimized chitosan-coated nanostructured lipid carriers: A promising strategy for enhanced wound healing and tissue regeneration","authors":"Fatemeh Barari ,&nbsp;Samane Maghsoudian ,&nbsp;Vajihe Alinezhad ,&nbsp;Seyedeh Melika Ahmadi ,&nbsp;Fereshteh Talebpour Amiri ,&nbsp;Yousef Fatahi ,&nbsp;Mohammad Barari ,&nbsp;Pedram Ebrahimnejad ,&nbsp;Jafar Akbari ,&nbsp;Fatemeh Atyabi ,&nbsp;Rassoul Dinarvand","doi":"10.1016/j.jddst.2025.107052","DOIUrl":"10.1016/j.jddst.2025.107052","url":null,"abstract":"<div><div>The development of innovative systems with antioxidant activity and controlled release capabilities is crucial for efficient wound healing and tissue regeneration. In this study, we developed a Carbopol based gel containing astaxanthin (AST) loaded chitosan-coated nanostructured lipid carriers (CS-NLCs). This system aimed to enhance stability, biocompatibility, sustained antioxidant properties, skin permeability, and minimize AST-related side effects. AST was encapsulated in NLCs using a hot homogenization ultrasonication method. Structural and morphological characteristics of nanoparticles were analyzed through TEM, FE-SEM, DSC, DLS, and XRD, confirming successful AST encapsulation in NLCs and CS coating. SEM analysis revealed particle sizes of 80 ± 6.6 nm for AST-NLCs and 221.4 ± 39.2 nm for CS-AST-NLCs. The encapsulation efficiency was above 85.45 %, with a loading content of 4.04 % for AST-NLCs. The antioxidant activity, assessed through DPPH, hydroxyl radical inhibition, and DCFH assays, demonstrated that AST-NLC-CS and AST-NLC exhibited significantly enhanced antioxidant performance compared to free AST. MTT assay confirmed biocompatibility of CS-AST-NLC formulation, with cell viability reaching 103.6 ± 1.1 % over 72 h. <em>In vitro</em> cell migration studies demonstrated effectiveness of AST-NLC-CS, with 85.9 ± 4.4 % fibroblast (L929) cell migration to wound site during 24 h. <em>In vivo</em> studies revealed accelerated wound healing and tissue regeneration with AST-NLC-CS/gel, leaving only 9.5 ± 2.2 % of the wound area on day 11 post-treatment compared to other groups. Histopathological analyses using H&amp;E and MT staining of incision wounds in male wistar Rats treated with CS-AST-NLC/Gel showed enhanced collagen deposition, more effective neovascularization, faster epithelialization, and reduced inflammatory cell infiltration compared to control group. This multifunctional system demonstrated great potential for improving wound healing and advancing tissue regeneration strategies.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107052"},"PeriodicalIF":4.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploiting protein-glycan interactions to design precision nanoparticles to inhibit viral infections: A review","authors":"Dhaarini Sakharayapatna Yogaraju ,&nbsp;Vaibhav Sunithi Sony ,&nbsp;Akshath Uchangi Satyaprasad","doi":"10.1016/j.jddst.2025.107074","DOIUrl":"10.1016/j.jddst.2025.107074","url":null,"abstract":"<div><div>Viral infections are alarmingly rising, and some viral infections have pandemic potential. One major limitation of current treatment strategies is their inability to inhibit various viral infections and the availability of vaccines. The glycoproteins involved in virus-host interactions such as heparan sulfate proteoglycans, Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN/R), Mannose binding lectin etc. are key to design precision nanoparticles. The glycans involved in binding to these glycan-binding proteins are polymeric mannose/fucose/sialic acid etc. The efficient interaction between these glycans and glycoproteins in host cells is dictated by ligand density, distribution, inter-glycan distance, etc. To design nanoparticle-glycan mimics that can competitively bind to viruses and deactivate them, the surface of the nanoparticles are functionalized with synthetic polymers like polyethylene glycol to make them biocompatible, and 11-mercapto-undecane sulfonate, Poly(styrene sulfonate), Mono/di mannose, Sialic acid etc. The synthesis and ligand exchange chemistry is exploited to design precision nanoparticles with defined ligand density, inter-ligand distance etc. that can spatially match the host glycoproteins thereby bind with very high affinity. This review focuses on glycoproteins involved in virus glycan recognition, common mechanism of viral infection that could be exploited to design precision nanoparticles using various ligands, limitations, and future scope.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107074"},"PeriodicalIF":4.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal teriflunomide-loaded lipid-based nanocarriers an improved remyelination potential in multiple Sclerosis: In-vitro, pharmacological, and toxicological assessments","authors":"Dnyandev Gadhave ,&nbsp;Vishal Babar ,&nbsp;Shubham Khot ,&nbsp;Nitin Waghamode ,&nbsp;Chandrakant Kokare","doi":"10.1016/j.jddst.2025.107072","DOIUrl":"10.1016/j.jddst.2025.107072","url":null,"abstract":"<div><div>A potential risk of demyelination is the manifestation of autoimmune disorders affecting the central nervous system, which leads to neurodegeneration and neuropsychiatric complications in patients. Conventional delivery approaches for therapeutics in brain disorders face limitations imposed by the blood-brain barrier. It is crucial to explore biomedical applications of nanoemulsion and understand the interaction between protein-drug-loaded nanoemulsions and their targeted effect on cellular receptors. Hence, the targeted efficacy of protein bovine serum albumin (BSA) with teriflunomide (TFM) on activated microglia was estimated through a virtual molecular docking technique. Results affirm that the combination of BSA and TFM successfully targets activated microglia. Hence, this study was undertaken to formulate TFM nanoemulsion-loaded with BSA and chitosan (CH) nanocarriers (TFM-BSA-CH-NCs) and investigate their therapeutic efficacy in multiple sclerosis through intranasal delivery. TFM-BSA-CH-NCs were then assessed for globule size, ζ-potential, %EE, viscosity, and <em>ex-vivo</em> mucoadhesive strength, and results were found as 92.2 ± 4.0 nm, +18.3 ± 0.8 mV, 98.8 ± 0.3 %, 17.4 ± 1.2 cP, and 10.7 ± 0.3 g, respectively. TFM-BSA-CH-NCs showed sustained release and followed the Hixon-Crowel cube root model. Further, rapid remyelination was obtained in cuprizone-induced demyelinating animals after being treated with TFM-BSA-CH-NCs, which proved its efficacy. However, TFM-BSA-CH-NCs reduced the hepatotoxic potential of TFM as well as maintained TNF-α, IL-1β, GFAP, and GABA levels in experimental animals. Therefore, intranasal TFM-BSA-CH-NCs is applicable to overcome the limitations of conventional therapy and improve therapeutic potential in multiple sclerosis patients.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107072"},"PeriodicalIF":4.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injectable self-healing dynamic aldehyde-gellan gum-based hydrogel nanocomposite with enhanced antibacterial and antioxidant wound dressing to alleviate chronic skin wound","authors":"Aniruddha Dan ,&nbsp;Hemant Singh ,&nbsp;Tishira K. Shah ,&nbsp;Wajid Mohammad Sheikh ,&nbsp;Majid Shafi ,&nbsp;Laxmanan Karthikeyan ,&nbsp;Jasmeena Jan ,&nbsp;Shabir Hassan ,&nbsp;Showkeen Muzamil Bashir ,&nbsp;Mukesh Dhanka","doi":"10.1016/j.jddst.2025.107075","DOIUrl":"10.1016/j.jddst.2025.107075","url":null,"abstract":"<div><div>The difficult-to-heal wounds present a significant challenge for current treatment modalities due to factors such as impaired tissue microenvironments, disrupted inflammatory balance, impaired cellular proliferation, and opportunistic bacterial infections. Drawing inspiration from the biocompatibility of biological macromolecules, we fabricated injectable nanocomposite hydrogels using oxidized gellan gum, gelatin, and polyethyleneimine (PEI). The hydrogels demonstrated remarkable shear-thinning properties due to the reversible imine bonds. The incorporation of quercetin-loaded zein nanoparticles (QZnps) further enhanced the bioactivity of the hydrogels, including improved cell proliferation, antibacterial efficacy, and controlled release of quercetin in vitro. In vivo studies demonstrated that these engineered nanocomposite hydrogels significantly accelerated wound contraction rates in full-thickness wounds in rats. This was achieved through enhanced collagen deposition, optimized re-epithelialization, tissue remodeling, and the restoration of inflammatory balance. These dynamic QZnps-loaded nanocomposite hydrogels offer a promising approach for the treatment of chronic full-thickness wounds, obviating the need for additional antibiotics, traditional drugs, or exogenous cytokines. This versatile hydrogel system holds great potential for the effective management of chronic full-thickness wound healing.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107075"},"PeriodicalIF":4.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced antitumor effects of interferon-stimulating DNA and magnetic hyperthermia in a breast cancer rat model","authors":"Kübra Solak ,&nbsp;Ahmet Mavi ,&nbsp;Ali Taghizadehghalehjoughi ,&nbsp;Serkan Yildirim ,&nbsp;Sıdıka Genc ,&nbsp;Ahmet Hacimuftuoglu","doi":"10.1016/j.jddst.2025.107044","DOIUrl":"10.1016/j.jddst.2025.107044","url":null,"abstract":"<div><div>This study examined the targeted delivery of interferon-stimulating DNA (ISD) by magnetic nanoparticles (MNPs) against breast cancer in a rat model. We synthesized Fe₃O₄ MNPs and modified their surface with silica and polyethyleneimine (Fe₃O₄@SiO₂@PEI) for biocompatibility and water dispersibility. A folic acid-linked polyethyleneimine (PEI-FA) was synthesized to enhance the targeted delivery of ISD to the breast cancer cells. The ISD-loaded Fe₃O₄@SiO₂@PEI MNPs at low concentrations significantly affected breast cancer cells by contributing to reduced oxidative stress, triggering a pathway to stimulate interferon-beta production. However, they did not affect non-tumorigenic MCF-10A cells. Furthermore, treating ISD-loaded MNPs significantly decreased the quantity of tumor cells in a rat model of breast cancer. Magnetic hyperthermia (MHT) improved the therapeutic efficacy by elevating the temperature of ISD-loaded MNPs over 40 °C under an alternating current magnetic field. In the rat model, there was an over 5-fold difference in tumor mass between the untreated groups and those treated with ISD and MHT. We observed that apoptosis, inflammation, and DNA damage markers were significantly changed in the tumor tissues of the rats. Despite the low amount of material (max 2 μg ISD) and short exposure to the magnetic field (1 h), the treatment results demonstrated encouraging outcomes.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107044"},"PeriodicalIF":4.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rutin-containing cyclodextrin nanosystems: a possible strategy for dietary supplementation in diabetics","authors":"Maddalena Sguizzato ,&nbsp;Francesca Ferrara ,&nbsp;Marilena Sisto ,&nbsp;Markus Drechsler ,&nbsp;Eleonora Gallerani ,&nbsp;Francesco Nicoli ,&nbsp;Rita Cortesi","doi":"10.1016/j.jddst.2025.107065","DOIUrl":"10.1016/j.jddst.2025.107065","url":null,"abstract":"<div><div>The flavonoid rutin is an active ingredient with multiple health benefits featuring antioxidant, anti-inflammatory, cardiovascular, neuroprotective, anti-diabetic and anti-tumor activity, unfortunately characterized by physico-chemical instability and poor solubility in aqueous environment. The present study investigates the use of nanosystems for the delivery of rutin through oral administration for a possible dietary supplementation. In this view, rutin-containing cyclodextrins and rutin-in-cyclodextrin-in-liposomes (R-CL) have been studied. R-CL, obtained by the “thin film hydration” method, were initially homogeneous in size, but increased in the average diameter over time. R-CL showed greater encapsulation efficiency and stability of rutin over time compared to cyclodextrin complexes. R-CL were stable in term of rutin content and physically within 30 days of storage in a cool environment, showing no phase separation phenomena. The dialysis study through a Wistar rat small intestine fragment, demonstrated an increasing release of rutin from R-CL, reaching the plateau around the sixth hour. The use of a gastrointestinal fluid simulator within the selected biological fragment, led to a more linear and gradual release profile over time, still obtaining a complete release of the drug around the sixth hour. The <em>in vitro</em> experiments on HepG2 cells evidenced no cytotoxic effect for both R-CL and cyclodextrin-complex and a strong and significant increase in glucose uptake levels promoted by R-CL with respect to untreated cells, as well as to the other formulations. The data suggest that the formulation strategy based on the vesicular cyclodextrin system improves the biological effect of rutin on cells. However, further studies will be necessary to confirm the activity of rutin as food supplementation.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107065"},"PeriodicalIF":4.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On eco-friendliness and 3D printing of pharmaceuticals","authors":"Jolieke van der Veen ,&nbsp;Giulia Callegaro ,&nbsp;Stefano Cucurachi ,&nbsp;Fereshteh Shokri","doi":"10.1016/j.jddst.2025.107071","DOIUrl":"10.1016/j.jddst.2025.107071","url":null,"abstract":"<div><div>3D drug printing is an innovative approach to tablet fabrication, offering significant potential for personalized medicine by enabling drug customization and addressing drug shortage. This method reduces reliance on mass production and promotes decentralised pharmaceutical manufacturing through compact, portable equipment. As the technology gains wider adoption, evaluating its environmental impact becomes crucial.</div><div>Producing 3D-printed tablets requires printable excipients in addition to active pharmaceutical ingredients (APIs) to ensure product stability and efficacy. This study evaluates the eco-friendliness of these excipients by examining their aquatic toxicity, biodegradability, and environmental persistence. The analysis draws on data from available literature, supplier information, and databases.</div><div>Moreover, we briefly discuss the sustainability aspects of 3D drug printing hardware, including design considerations and energy consumption. A focus is placed on two widely utilized techniques in this field: fused deposition modeling (FDM) and semi-solid extrusion (SSE) printing. These methods exemplify cutting-edge advancements in 3D pharmaceutical manufacturing.</div><div>This perspective review thus provides a comprehensive assessment of the environmental sustainability of 3D-printed drug formulations and machinery. By offering insights into eco-friendly practices, it serves as a foundation for sustainable development in both industrial and pharmacy applications.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107071"},"PeriodicalIF":4.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEP-1 fused to glutathione peroxidase from Trichoderma reesei: a safe and effective antioxidant active ingredient for cutaneous applications","authors":"Patricia P. Adriani ,&nbsp;Luciana B. Lopes ,&nbsp;Gabriel S. de Oliveira ,&nbsp;Jessica R. Nunes ,&nbsp;Giovanna C. Salata ,&nbsp;Myrian T.P. Fernandes ,&nbsp;Gustavo Roncoli Reigado ,&nbsp;Denisse Esther Mallaupoma Camarena ,&nbsp;Silvya S. Maria-Engler ,&nbsp;Marcio V.B. Dias ,&nbsp;Viviane A. Nunes ,&nbsp;Felipe S. Chambergo","doi":"10.1016/j.jddst.2025.107054","DOIUrl":"10.1016/j.jddst.2025.107054","url":null,"abstract":"<div><div>Skin aging is associated with an increase in the generation of reactive oxygen species (ROS), leading to progressive cellular damage. Simultaneously, the skin's antioxidant mechanisms become less effective, compromising its defense capacity. Although the use of antioxidant enzymes in cosmetic and dermatological products is promising, the topical application of these molecules is hindered by their physicochemical characteristics. An effective alternative is using cell-penetrating peptides (CPPs), which facilitate the transduction of macromolecules, including enzymes, through the skin barrier. Here, an antioxidant system composed of the glutathione peroxidase enzyme from the fungus <em>Trichoderma reesei</em> (TrGPx) fused to the CPP Pep-1 (PEP1-TrGPx) was developed as an alternative active antioxidant ingredient for skin treatment. The efficacy and safety of this system were evaluated as a potential cosmetic and dermatological application. The results showed that PEP1-TrGPx was effectively delivered and protected human keratinocyte (HaCaT) epidermal cells against oxidative stress induced by H₂O₂ at low concentrations without showing a significant cytotoxic effect. Furthermore, the system demonstrated no potential for skin or ocular irritation. These findings suggest that PEP1-TrGPx is a promising, stable, safe, and effective active ingredient with great potential for therapeutic and cosmetic applications. It offers an effective strategy for skin care and mitigating oxidative stress-related damage associated with aging.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"110 ","pages":"Article 107054"},"PeriodicalIF":4.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194828","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}