Drug Delivery最新文献

{"title":"Unlocking the \"undruggable\": current landscape and emerging frontiers in lysosomal receptor-mediated protein degradation.","authors":"Yi-Meng Ma, Hou-Fu Xia, Yi-Lei Xiao, Zi-Li Yu","doi":"10.1080/10717544.2026.2636323","DOIUrl":"10.1080/10717544.2026.2636323","url":null,"abstract":"<p><p>Extracellular and membrane-associated proteins are essential in signal transmission, immunological control, and disease pathogenesis; nonetheless, their 'undruggable' characteristics have historically impeded drug discovery. The targeted protein degradation (TPD) technologies provide innovative solutions to address this dilemma. Despite the rapid advancement of techniques such as Proteolysis-targeting chimera (PROTACs) that utilize the Ubiquitin-proteasome system (UPS), their applicability is limited to intracellular proteins. Lysosome-targeting chimeras (LYTACs), utilizing the endocytosis-lysosomal route, facilitate the selective degradation of secreted and transmembrane proteins, thereby considerably broadening the target spectrum of TPD. Since its inception in 2020, the LYTAC platform has consistently progressed, incorporating several Lysosome-targeting receptor (LTR) targeting techniques and innovative delivery vehicles, including aptamers, peptides, and nanoparticles. It has exhibited promise in oncology, neurological conditions, and immune-mediated disorders. Nevertheless, LYTAC encounters several obstacles, such as intricate ligand design, potential immunogenicity, inadequate tissue selectivity, and restricted clinical validation. Platforms and tactics designed to improve degrading efficiency, broaden disease applicability, and facilitate clinical translation signify interesting research avenues in this domain. This paper presents a thorough evaluation of the research advancements and application potential of LYTAC technology, while examining significant limitations and future direction of development.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2636323"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12943813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microneedle-based injection of Fungizone/Amphotericin B: an effective treatment for American cutaneous leishmaniasis in mice.","authors":"Ryan H Huston, Blake Cox, Chaitenya Verma, Thalia Pacheco-Fernandez, Greta Volpedo, M Junaid Dar, Yulian Mercado, Abigail R Wharton, Max Gessner, Nandu Purayil, Ivana Arsovska, Leah Watkins, Junqi Lu, Jennifer Y Zhang, Andrew Sachan, Roger J Narayan, Abhay R Satoskar","doi":"10.1080/10717544.2026.2665882","DOIUrl":"10.1080/10717544.2026.2665882","url":null,"abstract":"<p><p>Amphotericin B (AmB) is a potent, accessible, FDA-approved drug against CL with damaging side effects. While newer lipid formulations have less toxicity, limitations include affordability and cold-chain requirements. CL affects mostly impoverished communities, which complicates travel to urban hospitals for treatment. Therefore, an off-clinic drug delivery system is desirable. Microneedles can deliver AmB directly to localized CL lesions, which we hypothesized would limit parasite growth without systemic toxicity. Thus, a three-by-three array of 1 mm tall stainless steel hollow microneedles was evaluated in this study. To test their efficacy, we utilized <i>Leishmania mexicana-</i>infected mice to model American CL. Following 20- and 10-consecutive day microneedle treatments (<i>n</i> = 5/group), the 20-day trials more strongly limited lesion growth by up to 2.8 mm versus a maximum 1.1 mm difference between the drug and placebo groups in the 10-day trial (<i>p</i> = 0.008, <i>p</i> = 0.075, respectively). Also, treatments were associated with reduced parasitic burden weeks after treatment cessation, as assessed by limiting dilution (<i>p</i> = 0.057 for 10-day, <i>p</i> = 0.075 for 20-day; one-tailed Mann‒Whitney <i>U</i> test). No elevation of blood serum creatinine or blood urea nitrogen levels was observed, supporting the hypothesis of lessened kidney toxicity. Additionally, flow cytometry explorations showed differences in IL-17 and IFN-γ positivity, and histological changes were observed in the upper dermis. These promising results represent the first test of hollow microneedles for CL treatment and pave the way for further trials. The adoption of microneedles could reduce CL burden in affected communities because of their ease of use, efficacy, and safety with a pre-approved drug.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2665882"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human factors validation study of a disposable autoinjector (Bmab 1200 autoinjector) for subcutaneous delivery of Ustekinumab.","authors":"Sam Moses K, Rohini Kamaraj, Suryaprakash Konda Ramachary Subramanian","doi":"10.1080/10717544.2026.2680354","DOIUrl":"10.1080/10717544.2026.2680354","url":null,"abstract":"<p><p>Ustekinumab is approved for treating moderate to severe plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. The Bmab 1200 autoinjector is a simple, two-step device for subcutaneous ustekinumab biosimilar delivery. This was an in vitro, nonclinical, simulated-use human factors validation study to evaluate if intended users could safely and effectively use it. Ninety participants (recruited via purposive sampling) were enrolled (mean age: 43 years; range: 12-72 years), including adult and adolescent patients, lay caregivers, and healthcare professionals. Without formal training, participants performed simulated injections into foam pads. Test personnel observed, documented, debriefed, and reported any errors made by participants while completing assigned tasks and sub-tasks. Each participant was observed throughout the session and observational and performance data were collected in real time by data logger. Performance measures included injection success rates, use errors, and 24 knowledge tasks. Across these knowledge tasks, participants were required to locate, identify, and understand 28 distinct measures. Participants also provided feedback on usability and confidence levels. All participants (100%) completed unaided dose injections. A total of 20 use errors were documented: hand hygiene (<i>n</i> = 8), site preparation (<i>n</i> = 5), and device handling (<i>n</i> = 7), none causing device damage or failed delivery. The knowledge task success rate was 99.6% (2,511/2,520 measures). Nine use errors (study artifacts or inattention to instructions) occurred only among caregivers. All participants expressed confidence in safe dosing and found the device user-friendly. The Bmab 1200 autoinjector demonstrated high usability and safety across diverse users for ustekinumab biosimilar delivery in chronic autoimmune conditions.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2680354"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FEA-guided co-design of bubble microneedles: controlled tip separation for rapid transdermal and sublingual delivery.","authors":"Changzhao Jiang, Jing Yang, Mengxuan Gao, Yi He, Weiwei Liao, Hang Chen, Zhixiong Wang, Shibo Ying, Xiaohua Tao, Xiumei Jiang, Jincui Ye","doi":"10.1080/10717544.2026.2667564","DOIUrl":"10.1080/10717544.2026.2667564","url":null,"abstract":"<p><p>Separable bubble microneedles (BMNs) incorporate an internal cavity that enables tip-confined loading and controlled tip-baseplate separation, yet their design has largely relied on empirical iteration. Here, we present a finite element analysis (FEA)-guided co-design framework that co-optimizes BMN geometry, cavity parameters, and matrix properties to enable controlled tip-baseplate separation while preserving insertion robustness. Simulations predicted stress localization at the engineered cavity, thereby reducing the transverse separation force without compromising axial failure load. Using minoxidil sulfate-loaded BMNs (MXS-BMNs) and insulin-loaded BMNs (INS-BMNs) as transdermal and sublingual models, respectively, the measured transverse separation forces were 5.23 N and 4.17 N, compared with FEA predictions of 6.16 N and 4.79 N. The corresponding axial failure loads were 0.13 N and 0.28 N, exceeding reported penetration thresholds for skin and sublingual mucosa. Release studies showed that more than 80% of the payload was liberated within 10 min. In ex vivo Franz diffusion tests, MXS-BMNs achieved approximately sevenfold greater cumulative minoxidil permeation over 24 h than an equivalent-dose topical gel. In vivo, MXS-BMNs accelerated hair regrowth in C57BL/6 mice, and INS-BMNs produced rapid and sustained glucose lowering in diabetic rats comparable to subcutaneous injection via an injection-free mucosal route. Collectively, this work establishes a semi-quantitative screening approach that reduces empirical iteration and expedites the development of separable microneedle systems for rapid transdermal and sublingual delivery.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2667564"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sprayable NIR/pH-responsive NSC/PF127 hydrogel loaded with MoO₂, ciprofloxacin, and FGF-2 for enhanced antibacterial and pro-regenerative infected wound healing.","authors":"Zhirui Li, Mingxing Lei, Chen Chen, Shuaishuai Li, Guoqi Wang","doi":"10.1080/10717544.2026.2719063","DOIUrl":"10.1080/10717544.2026.2719063","url":null,"abstract":"<p><p>Infected wounds represent a significant clinical burden owing to persistent infection, excessive inflammation, and impaired tissue regeneration. To overcome these limitations, we developed a sprayable <i>N</i>-succinyl chitosan/Pluronic F127 (NSC/PF127) hydrogel incorporating MoO₂ nanoparticles, ciprofloxacin, and fibroblast growth factor-2 (FGF-2). At body temperature, the hydrogel rapidly transitions from a solution to a gel and responds to both pH changes and near-infrared (NIR) irradiation. MoO₂ exhibits NIR-mediated photothermal activity, while CIP and FGF-2 are released in a sustained and pH-dependent manner, thereby maintaining antibacterial efficacy and growth factor bioactivity. <i>In vitro</i> studies demonstrated excellent cytocompatibility and significantly enhanced fibroblast and keratinocyte migration. The combined photothermal effect and antibiotic therapy effectively suppressed bacterial growth and disrupted established biofilms. In a rat model of <i>Staphylococcus aureus</i>-infected full-thickness wounds, the hydrogel composite significantly accelerated healing, reduced inflammation, promoted collagen deposition and angiogenesis, and enhanced tissue regeneration. Biochemical and gene expression analyses further indicated reduced oxidative stress and improved tissue regeneration. This multifunctional, sprayable hydrogel combines targeted antibacterial action with sustained pro-regenerative signaling, offering a promising strategy for further preclinical investigations of infected wound management.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2719063"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic epigenetic modulation and ferroptosis induction via codelivery of Decitabine and Sorafenib for potent anti-tumor therapy.","authors":"Yujie Xing, Xuan Zhang, Rui Wang, Yu Zhou, Ke Sun, Fan Yu, Xue Zheng, Wei Zhao","doi":"10.1080/10717544.2026.2726824","DOIUrl":"10.1080/10717544.2026.2726824","url":null,"abstract":"<p><p>Despite considerable advances in cancer therapy, the intrinsic heterogeneity of malignant cells continues to compromise therapeutic efficacy with conventional monotherapies, driving the need for combination treatments to achieve more durable and complete responses. The limited efficacy of conventional chemotherapy is largely attributable to the immunosuppressive tumor microenvironment, which is frequently perpetuated by epigenetic mechanisms, including aberrant DNA methylation. To overcome these limitations, we hypothesized that Decitabine (Dac)-mediated sensitization could dramatically enhance Sorafenib (Sor)-induced ferroptosis, and to test this synergy, we developed an innovative biomimetic codelivery platform comprising polymer micelles loaded with Sor surface-coated with exosomes encapsulating Dac (Exo&PM/D + S). This platform facilitates codelivery, enabling Dac-mediated DNA hypomethylation to remodel the tumor microenvironment and promote Sor-triggered ferroptosis. <i>In vitro</i>, Exo&PM/D + S exhibited potent anti-tumor activity by concurrently enhancing DNA demethylation and ROS accumulation. In mouse neuroblastoma models, the system significantly suppressed tumor growth, stimulated antitumor immunity, and extended survival. Mechanistic studies confirmed that Dac potentiates Sor-induced ferroptosis through epigenetic modulation. Thus, Exo&PM/D + S represents a promising nanotherapeutic strategy that synergizes epigenetic modulation with ferroptosis induction for enhanced anti-tumor efficacy.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2726824"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineered extracellular vesicles integrating anti-EphA2 recognition and oxaliplatin delivery for pancreatic cancer therapy.","authors":"Shi-Wei Chao, Wan-Chi Tsai, Yung-Han Chang, Shan-Jou Chen, Chia-Tse Li, Jo-Han Fan, Bo-Cheng Huang, Shih-Ting Hong, Hong-Ren Wang, Yu-Ting Huang, Ming-Yii Huang, Chih-Hung Chuang","doi":"10.1080/10717544.2026.2728215","DOIUrl":"10.1080/10717544.2026.2728215","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid tumors due to its dense desmoplastic stroma, poor vascular perfusion, and the limited intratumoral delivery of chemotherapeutic agents such as oxaliplatin (OXA). Extracellular vesicles (EVs) offer a biocompatible platform for drug delivery, yet their intrinsic lack of tumor specificity constrains therapeutic efficacy. Ephrin type-A receptor 2 (EphA2), which is highly expressed and efficiently internalized in PDAC, represents an attractive molecular target for guiding EVs into tumor cells. In this study, we engineered HEK293T-derived EVs to display membrane-anchored anti-EphA2 Fab fragments and encapsulate OXA (EVs-EphA2/OXA) as a targeted delivery system for PDAC therapy. Stable producer cells expressed the engineered Fab on the plasma membrane and released vesicles that retained canonical EV markers and robust antigen-binding capability. EVs-EphA2 demonstrated selective uptake into EphA2-positive AsPC-1 and BxPC-3 cells and induced significantly greater cytotoxicity than free OXA or untargeted EVs/OXA in vitro. In xenograft models, EVs-EphA2/OXA achieved the most pronounced tumor suppression, accompanied by increased γH2AX-associated DNA damage, enhanced TUNEL-positive apoptosis, and preferential tumor accumulation in biodistribution imaging. These findings demonstrate that EphA2-targeted EVs can substantially improve intratumoral delivery of OXA and amplify antitumor efficacy, supporting EVs-EphA2/OXA as a promising platform for receptor-guided chemotherapy in PDAC.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2728215"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acid-responsive nanoparticles with microneedles for anti‑inflammatory sonodynamic therapy of gouty arthritis.","authors":"Jiaqi Weng, Lili Feng, Binghui Xie, Linxiao Liu, Shulin Shen, Xuechao Chen, Liting Wang, Yueyue Xie, Jianhua Yao, Laurent David, Qinying Yan","doi":"10.1080/10717544.2026.2743337","DOIUrl":"10.1080/10717544.2026.2743337","url":null,"abstract":"<p><p>The pathological microenvironment of acute gouty arthritis (AGA) features local tissue acidification and the release of a storm of pro-inflammatory cytokines. To address this dual challenge, we engineered an acid-responsive curcumin-loaded nanoparticles microneedle system (Cur-PNPs@MN) that delivers curcumin with pH-triggered release and anti-inflammatory activity. This integrated platform combines a hyaluronic acid (HA)-based dissolving microneedle for localized transdermal delivery of acid-degradable PCADK (poly (cyclohexane-1,4-diyl acetone dimethylene ketal)) curcumin nanoparticles (Cur-PNPs), which are designed for pH-triggered curcumin release at the pathological site. Together, they deliver curcumin, a dual-function agent acting both as an anti-inflammatory compound and a nanoenhanced sonosensitizer. <i>In vitro</i>, the system exhibited acid-responsive drug release and also promoted macrophage uptake, achieving significant curcumin accumulation within 1 hour and saturation by 4 hours. Moreover, it could generate potent ultrasound-induced reactive oxygen species (ROS). The ROS generation capability of Cur-PNPs was 1.47-fold higher than that of Cur‑aggregates, resulting in anapoptosis rate of 29.9% in M1 macrophages. <i>In vivo,</i> the chemo-sonodynamic therapy (Cur-PNPs@MN+Ultrasound (US)) in a rat AGA model significantly alleviated joint swelling and inflammatory infiltration, while drastically suppressing pro-inflammatory cytokines, with IL-1β decreasing from 170.3 to 67.3 pg/mL, TNF-<i>α</i> from 20.8 to 5.9 pg/mL, and IL-6 from 140.9 to 48.2 pg/mL, and achieved therapeutic efficacy comparable to conventional drugs. This work demonstrates a synergistic chemo‑sonodynamic strategy by coupling pH-triggered curcumin release with ultrasound-enhanced ROS generation. This acid-responsive therapeutic strategy enhances anti-inflammatory efficacy and reduction of M1-associated inflammatory responses, offering an effective approach for AGA therapy.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2743337"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming the nuclear barrier in nonviral gene therapy: mechanisms, carrier design, and translational perspectives on NLS peptide and DNA targeting sequence strategies.","authors":"Taegeun Lee, Ye-Rin Kim, Euijin Lee, Sae-Ock Oh","doi":"10.1080/10717544.2026.2741456","DOIUrl":"10.1080/10717544.2026.2741456","url":null,"abstract":"<p><p>Efficient delivery of plasmid DNA (pDNA) into the nucleus remains a major bottleneck in nonviral gene therapy, particularly in post-mitotic and slowly dividing cells where the nuclear envelope constitutes a permanent barrier to passive entry. This review considers the two main strategies for active nuclear targeting: nuclear localisation signal (NLS) peptides, which recruit importin-α/β receptors directly to DNA cargo, and DNA nuclear targeting sequences (DTS), which exploit NLS-bearing transcription factors to mediate piggyback nuclear import. Rather than re-cataloguing nuclear import biology, we focus on the conditions under which each strategy succeeds or fails, incorporating advances in nuclear pore complex architecture and permeability, karyopherin-FG-nucleoporin electrostatics, and cytoplasmic constraints such as barrier-to-autointegration factor (BAF)-mediated clustering of exogenous DNA. NLS classes are compared with universal (SV40 enhancer), inducible (NF-κB) and tissue-specific (SMGA, SP-C, T1α) DTS elements, and four chemical coupling strategies are evaluated across peptide-, polymer- and lipid-based nanoassemblies. To address the near-absence of NLS/DTS mechanisms in current clinical pDNA programmes, we propose the Nuclear Accessibility Index (NAI): a three-axis framework integrating cell division status, carrier-DNA accessibility and intracellular signalling context. Treating the NAI as an axis vector rather than a summed score defines permissive, conditional and excluded regions of the design space. Two matter in practice: one in which highly proliferative cells render active targeting redundant, and one in which the rate-limiting problem is carrier engineering rather than the addition of a signal. The NAI offers design principles for nuclear-targeted nanocarriers and defines the preconditions for therapeutically relevant active import.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2741456"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-mechanism vitamin C delivery by polyethylene glycol-23 glyceryl distearate-based niosomes via SVCT2 induction and enhanced transdermal penetration.","authors":"Tatsuro Miyoshi, Brian C Keller, Sui Nakagawa, Takashi Ashino, Asuka Kaizaki-Mitsumoto, Satoshi Numazawa","doi":"10.1080/10717544.2026.2681287","DOIUrl":"10.1080/10717544.2026.2681287","url":null,"abstract":"<p><p>Polyethylene glycol-23 glyceryl distearate (GDS-23)-a noisome-forming diacylglycerol-polyethylene glycol-based nonionic surfactant-functions as a nanocarrier for drug delivery systems (DDS) and an enhancer of endogenous antioxidant capacity through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Here, we evaluated the potential of GDS-23 as a multifunctional DDS carrier by investigating the combined contribution of (i) improved transdermal delivery mediated by niosomal DDS and (ii) increased cellular uptake associated with induction of antioxidant-related transporters, using protection against oxidative-stress-induced tissue damage as a functional readout. We determined whether GDS-23 modulates the expression of the antioxidant-related transporters xCT and SVCTs through Nrf2 activation. In normal human epidermal keratinocytes, GDS-23 treatment significantly upregulated the mRNA expression of <i>xCT</i> (<i>SLC7A11</i>; cystine/glutamate antiporter) and sodium-dependent vitamin C transporter 2 (<i>SVCT2</i>). The induction was diminished by an Nrf2 activation inhibitor (K67), indicating involvement of the Nrf2 pathway. Furthermore, evaluation using a three-dimensional reconstructed epidermis model with calcein sodium as a fluorescent tracer revealed that GDS-23-based niosomes facilitated skin permeation. When L-ascorbic acid or cysteine was encapsulated within these niosomes, hydroquinone-induced oxidative tissue damage was attenuated, with the L-ascorbic acid-loaded niosomes exhibiting the most prominent protective effect. Overall, this study shows that Nrf2 activation contributes to <i>SVCT2</i> induction and that GDS-23 is a multifunctional DDS nanocarrier that enhances skin permeation and may promote intracellular uptake by upregulating antioxidant-related transporters. These findings highlight the therapeutic potential of combining functional nanocarriers with entrapped bioactive molecules, offering a promising strategy for efficient treatment of skin disorders and antioxidant-based interventions.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2681287"},"PeriodicalIF":8.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}