Drug Delivery and Translational Research最新文献

{"title":"Development of a hydrophilic transdermal patch for combined delivery of sumatriptan and metoclopramide in migraine therapy.","authors":"Ariana Radmard, Ajay K Banga","doi":"10.1007/s13346-025-01874-0","DOIUrl":"https://doi.org/10.1007/s13346-025-01874-0","url":null,"abstract":"<p><p>Migraine, a prevalent neurological disorder, is known to significantly impact patients' quality of life. The effectiveness of oral medications is often hindered by nausea and vomiting, common migraine symptoms. In this study, a transdermal patch for the co-delivery of sumatriptan succinate and metoclopramide HCl was developed and evaluated, to offer a patient-friendly alternative for migraine management. This study evaluated the impact of chemical enhancers and hydrophilic formulations on drug permeation using dermatomed porcine ear skin. A combination of 25% w/w propylene glycol (PG) and 10% w/w dimethyl isosorbide (DMI) significantly enhanced the permeation of both drugs. Among four hydrophilic patch formulations, a matrix composed of a 1:3 ratio of polyvinylpyrrolidone (PVP) to hydroxypropyl methylcellulose (HPMC) demonstrated optimal drug delivery. Characterization tests, including coat weight, drug content uniformity, tack testing, and slide crystallization, were performed, all patches exhibited acceptable physical properties, including uniform drug content. The target therapeutic dose, equivalent to 4 mg subcutaneous injection of sumatriptan succinate and 10 mg oral metoclopramide HCL, was achieved within 8 h using a 60 cm² patch of the optimized formulation. Based on these findings, the developed transdermal patch could serve as a promising alternative for migraine management, potentially improving patient compliance and therapeutic outcomes.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110190","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":"Mitigating radioresistance mechanisms by polymer-lipid manganese dioxide nanoparticles enhances immunogenic cell death and antitumor immune response to facilitate abscopal effect in breast tumor models.","authors":"HoYin Lip, Abdulmottaleb Zetrini, Elliya Park, Ping Cai, Azhar Z Abbasi, Ting Huyan, Ibrahim Alradwan, Andrew M Rauth, Xiao Yu Wu","doi":"10.1007/s13346-025-01873-1","DOIUrl":"https://doi.org/10.1007/s13346-025-01873-1","url":null,"abstract":"<p><p>Breast cancer is the most diagnosed cancer and the second leading cause of cancer death in women. Although treatments with major anti-cancer modalities are largely successful, resistance to treatments including widely applied radiation therapy (RT) can occur due largely to the multifaceted mechanisms in the tumor microenvironment (TME). The present work investigated the ability of Polymer-Lipid-Manganese Dioxide Nanoparticles (PLMD) to overcome hypoxia-associated radioresistant mechanisms and enhance RT-induced immunogenic cell death (ICD) and anti-tumor immunity for inhibiting growth of primary and distant tumors (the abscopal effect). The results showed that PLMD plus RT significantly inhibited the clonogenic survival of murine EMT6 and 4T1 breast cancer cells under hypoxic condition compared to RT alone. Analysis of ICD biomarkers revealed that PLMD profoundly enhanced RT-induced ICD compared to RT alone in EMT6 and 4T1 cells under hypoxic conditions but not under normoxic conditions. In a syngeneic murine breast tumor model with 4T1 orthotopic tumor, the PLMD treatment reduced tumor hypoxia significantly; PLMD + RT combination therapy increased infiltration of cytotoxic CD8⁺ T cells and CD86⁺ macrophages and decreased infiltration of immunosuppressive Tregs and CD163⁺ macrophages, as compared to RT alone. Importantly, the PLMD + RT treatment generated an abscopal effect in a tumor growth experiment using a double-tumor model, where the growth of an untreated tumor was inhibited by treatment of a tumor grown on the opposite side. Overall, the PLMD + RT induced an anti-tumor immune response that inhibited both primary and distant tumor growths and extended median survival in the tumor model.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101671","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":"Bovine colostrum-derived extracellular vesicles modulate gut microbiota and alleviate atopic dermatitis via the gut-skin axis.","authors":"Daye Mun, Sangdon Ryu, Hyejin Choi, Min-Jin Kwak, Sangnam Oh, Younghoon Kim","doi":"10.1007/s13346-025-01875-z","DOIUrl":"https://doi.org/10.1007/s13346-025-01875-z","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by immune dysregulation and a disrupted gut-skin axis. Emerging evidence suggests that the gut microbiota and their metabolites play a critical role in pathogenesis and potential treatment of AD. However, therapeutic strategies targeting the gut microbiota that aim to alleviate AD remain underexplored. Therefore, this study investigated the potential of bovine colostrum-derived extracellular vesicles (BCEVs) to ameliorate AD symptoms by modulating the gut microbiota and intestinal metabolites. AD was induced in mice using 2,4-dinitrochlorobenzene, followed by the oral administration of BCEVs. Skin lesions were assessed histologically to evaluate disease severity. Allergic and immune responses were measured by analyzing serum immunoglobulin E (IgE) levels and cytokine profiles, including interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α). Gut microbiota composition was determined using 16 S rRNA gene sequencing, and the metabolomic profiling of intestinal samples was performed using gas chromatography-mass spectrometry to identify metabolites. BCEV treatment significantly alleviated skin lesions and reduced the serum IgE levels and the imbalance in IL-4 and TNF-α levels associated with AD induction. Gut microbiota analysis revealed that BCEVs restored microbial dysbiosis and improved the abundance of beneficial bacteria, and metabolomic analysis demonstrated elevated levels of lactic acid and other metabolites. These findings suggest that BCEVs alleviate AD symptoms by rebalancing the gut microbiota and intestinal metabolomes. This study emphasizes the importance of targeting the gut-skin axis as a novel strategy for AD treatment and provides evidence for the therapeutic potential of BCEVs in skin-related immune disorders.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076582","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":"Synergy of dissolving microneedles and ultrasound to enhance transdermal delivery for rheumatoid arthritis.","authors":"Wangrui Peng, MeeiChyn Goh, Jie Lan, Meng Du, Zhiyi Chen","doi":"10.1007/s13346-025-01876-y","DOIUrl":"https://doi.org/10.1007/s13346-025-01876-y","url":null,"abstract":"<p><p>Dissolving microneedles (DMNs) are an emerging transdermal drug delivery system that has gained increasing attention as an alternative to traditional oral and injectable methods for treating rheumatoid arthritis (RA). However, these DMNs encounter challenges related to insufficient drug diffusion through passive mechanisms. To address this issue, we developed biocompatible DMNs fabricated from hyaluronic acid (HA) loaded with ultrasound-responsive nanoparticles, aiming at enhancing drug permeation and diffusion through ultrasound (US) assistance. Methotrexate (MTX), a first-line treatment for RA, was encapsulated in poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles containing perfluoro-n-pentane (PFP), referred to as MTX-PFP-NPs. These nanoparticles were then incorporated into DMNs, designated as MTX-PFP-NPs@DMNs. Under the cavitation effect of ultrasound, PFP undergoes a phase transition that facilitates drug release and diffusion. The synergistic effect of the DMNs system and US were demonstrated in both an ex-vivo rat skin model and a collagen-induced arthritis (CIA) mouse model. The MTX-PFP-NPs@DMNs exhibited sufficient mechanical strength to penetrate the stratum corneum and dissolve completely within 20 min, enabling effective drug delivery. The synergistic effect of the DMNs system and US was evidenced by enhanced FITC penetration and diffusion in the ex-vivo rat skin model. Additionally, in vivo studied showed improved therapeutic efficacy in reducing joint swelling, bone erosion, cartilage damage, and pro-inflammatory cytokines level compared to only MTX-PFP-NPs@DMNs. This research underscores the promising integration of DMNs technology and US, offering a high-compliance approach to transdermal drug delivery that could significantly improve treatment outcomes for chronic conditions like RA.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076594","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":"Evaluation of ocular tolerability and bioavailability of tonabersat transfersomes ex vivo.","authors":"Santosh Bhujbal, Ilva D Rupenthal, Priyanka Agarwal","doi":"10.1007/s13346-025-01872-2","DOIUrl":"https://doi.org/10.1007/s13346-025-01872-2","url":null,"abstract":"<p><p>While transfersomes (TFS) have extensively been investigated as carriers for topical drug delivery to the skin, their application in ocular drug delivery remains largely unexplored. This study aimed to evaluate the tolerability, contact angle, and ocular penetration of tonabersat-loaded TFS using ex vivo models, with a focus on comparing drug distribution in different ocular tissues. A solution of tonabersat in medium chain triglycerides (MCT) was used as the control. Conjunctival tolerability was evaluated using the Hen's Egg Test on Chorioallantoic Membrane (HET-CAM), while the Bovine Corneal Opacity and Permeability (BCOP) assay was used to establish corneal tolerability. Drop contact angle on freshly excised bovine corneas was measured using a goniometer. Drug penetration into the cornea, conjunctiva, eyelid and sclera-choroid was evaluated using an ex vivo porcine whole eye model under simulated tear flow, 0.25, 0.5, 1, and 2 h after eyedrop application. Both the TFS and MCT formulations exhibited good conjunctival and corneal tolerability with the TFS contact angle on the corneal surface being lower than that of MCT. Significantly greater drug concentrations were achieved in all ocular tissues with the TFS eyedrop, with the C_max from TFS being at least 16-fold higher than that achieved with the MCT solution in the conjunctiva, eyelid and sclera-choroid, with the difference being greatest in the latter. Meanwhile, the corneal C_max was 6-fold greater with TFS. Interestingly, despite simulated tear flow, the T_max was observed at a later timepoint with TFS in all ocular tissues. Overall, this study demonstrates that TFS are well tolerated on the ocular surface and have the potential for sustained and targeted drug delivery to ocular tissues. Thus, they present a promising alternative for safe and effective ocular drug delivery.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968992","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 nanocomposite hydrogels for targeted intervention in cancer, wound healing, and bone and myocardial tissue engineering.","authors":"Ana Rita Pereira, Patrícia C Pires, Huma Hameed, Daniela Lopes, Joana Lopes, Inês Sousa-Oliveira, Soraya Babaie, Priscila Mazzola, Francisco Veiga, Ana Cláudia Paiva-Santos","doi":"10.1007/s13346-025-01864-2","DOIUrl":"https://doi.org/10.1007/s13346-025-01864-2","url":null,"abstract":"<p><p>Despite current medicine's fast-paced advances, many acute and chronic illnesses still lack truly effective and safe therapies. Cancer treatments often lead to off-target healthy tissue damage and poor therapeutic outcomes, wound standard treatments generally demonstrate poor healing efficacy and increased susceptibility to infection, and bone tissue engineering and myocardial tissue engineering can result in immunological rejection and limited availability. To tackle these issues, injectable hydrogels have emerged, and through the incorporation of nanoparticles, nanocomposite hydrogels have appeared as versatile platforms, offering improved biocompatibility, mechanical strength, stability, and precise controlled drug release, as well as targeted delivery with increased drug retention at the site of action, reducing systemic drug distribution to non-target sites. With the ability to deliver a diverse range of therapeutic entities, including low molecular weight drugs, proteins, antibodies, and even isolated cells, injectable nanocomposite hydrogels have revolutionized current therapies, working as multifunctional platforms capable of improving efficacy and safety in cancer treatment, including in chemotherapy, immunotherapy, photothermal therapy, magnetic hyperthermia, photodynamic therapy, chemodynamic therapy, radiotherapy, molecularly targeted therapy, and after tumor surgical removal, and in general, chronic diabetic or tumor-induced wound healing, as well as in bone tissue engineering and myocardial tissue engineering. This review provides a thorough summary and critical insight of current advances on injectable nanocomposite hydrogels as an innovative approach that could bring substantial contributions to biomedical research and clinical practice, with a focus on their applications in cancer therapy, wound healing management, and tissue engineering.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984962","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":"A framework for conducting clinical trials involving 3D printing of medicines at the point-of-care.","authors":"Carlos Javier Parramon-Teixido, Lucía Rodríguez-Pombo, Abdul W Basit, Anna Worsley, Carme Cañete-Ramírez, Carmen Alvarez-Lorenzo, Maria Josep Cabañas-Poy, Alvaro Goyanes","doi":"10.1007/s13346-025-01868-y","DOIUrl":"https://doi.org/10.1007/s13346-025-01868-y","url":null,"abstract":"<p><p>The integration of 3D printing (3DP) technologies into personalized medicine manufacture at the point-of-care is garnering significant interest due to its potential to create tailored drug products with precise dosages and other unique attributes. Both preclinical and clinical studies have demonstrated promising outcomes, including pharmacokinetic bioequivalence, improved patient acceptability, enhanced adherence, and the ability to produce consistent, reproducible dosage forms with accurate drug distribution. Some compounding pharmacies around the world are already incorporating 3DP into standard practice for simpler therapeutic treatments. However, further clinical evaluation is required for more complex treatments, such as multi-drug polypills. Conducting clinical trials involving 3DP technologies presents several challenges, including navigating evolving regulatory frameworks, addressing ethical and legal concerns, and complying with new point-of-care manufacturing guidelines. Although regulatory agencies are beginning to adapt their policies to accommodate 3DP, the absence of a comprehensive framework still creates uncertainty for pharmacists and healthcare providers. This article explores the planning and execution of clinical trials involving 3D printed medicines, with a focus on regulatory barriers, patient recruitment, compliance, and the integration of specialized equipment and expertise. It also discusses the implementation of 3DP for personalized drug manufacturing within hospital settings and offers guidance for obtaining clinical trial approval from the Spanish Agency for Medicine and Health Products (AEMPS). By providing these insights and recommendations, this article aims to support international harmonization and facilitate the adoption of 3DP technologies in clinical trials globally.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991423","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":"Radiolabelling and bioequivalence of modified Tamoxifen solid lipid nanoparticles as a targeted chemotherapeutic drug.","authors":"Rania S Abdel-Rashid, Eman S El-Leithy, Ismail T Ibrahim, Khaled M Attallah","doi":"10.1007/s13346-025-01865-1","DOIUrl":"https://doi.org/10.1007/s13346-025-01865-1","url":null,"abstract":"<p><p>There are several types of breast cancer where the breast's cells proliferate uncontrollably. A selective oestrogen receptor modulator called Tamoxifen citrate (TAM) is used to treat and prevent breast cancer in both men and women. TAM is classified as class II under the biopharmaceutical categorization system (BCS) of medications. It exhibits low plasma levels, which can result in therapeutic failure due to its poor water solubility. To improve its chemotherapeutic efficiency and drug targeting, nanotechnology was exploited. In this article, TAM-loaded SLNs were prepared, characterized, and radiolabelled with Technetium-99m ([^99mTc]Tc) using stannous salts followed by the assessment of their radiochemical efficiency and in vivo biodistribution compared to the radiolabelled free TAM ([^99mTc]Tc-TAM). The results showed that the concentration of lipid had a highly prominent effect on the particle size and encapsulation efficiency of the drug, where the best selected formula showed spherical, non-aggregated morphology with a 134.6 ± 0.3 nm size and 83.9 ± 2.5% drug encapsulation. The radiolabelling purity was more than 97.4%, and it was stable for at least 6 h. In solid tumor-bearing mice, [^99mTc]Tc-TAM-SLNs exhibited around 3 times more uptake than [^99mTc]Tc-TAM solution. Accordingly, [^99mTc]Tc-TAM-SLNs can be suggested as a useful targeted delivery strategy for chemotherapy drugs.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971854","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":"Post-encapsulation methods for the preparation of mRNA-LNPs.","authors":"Joanna Duffrène, Chloé Muzard, Johanne Seguin, Charlotte Izabelle, Thibaut Vrai, Tina Ejlalmanesh, Marianne Bombled, Samir Hamdi, Katia Lemdani, Khair Alhareth, Nathalie Mignet","doi":"10.1007/s13346-025-01866-0","DOIUrl":"https://doi.org/10.1007/s13346-025-01866-0","url":null,"abstract":"<p><p>Microfluidics mixing is the current lab-scale method used for producing mRNA-loaded lipid nanoparticles (mRNA-LNPs) thanks to reproducibility and robustness of microfluidic mixing. Despite these advantages, the production of small LNP volumes is associated with significant material waste. Given the high cost of synthetic mRNA, this waste can be a major limitation, particularly for early-stage screening of formulations. This study proposes alternative methods for mRNA-LNP formulation aiming to improve their stability for both formulation and mRNA screening, while reducing material waste on a research scale. Specifically, we investigated post-encapsulation of mRNA into pre-formed vesicles (PFVs) obtained by microfluidic mixing. These PFVs were complexed with mRNA by: (1) a microfluidic or (2) a manual pipetting method. The resulting mRNA-LNPs produced using these two post-encapsulation methods exhibit similar physicochemical properties and morphologies to those obtained by conventional microfluidic protocol. These mRNA-LNPs were assessed on in vitro and in vivo expression. mRNA-LNPs prepared by our alternative methods showed a similar transfection level compared to the conventional formulation taken as a control. The suitability of post-encapsulation methods to other lipids, mRNAs and microfluidic systems was also confirmed. This work offers robust, simple and economic alternative methods for preparing small volumes of mRNA-LNPs. The versatility of post-encapsulation methods allows to screen mRNA formulations in a wide range of laboratories. These methods could be applied to encapsulate tailored doses of mRNA and various mRNA constructs to achieve an optimal and personalized therapy.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982000","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":"Buccal application of microneedles coated with an optimized hydrogel containing naproxen and dexamethasone.","authors":"Joo-Young Kim, Yun-Sik Um, Young-Guk Na, Da-Eun Kim, Yo Han Song, Suyeon Hwang, Minki Jin, Jooyoung Kim, Seung-Ki Baek, Jong-Suep Baek, Hong-Ki Lee, Cheong-Weon Cho","doi":"10.1007/s13346-025-01870-4","DOIUrl":"https://doi.org/10.1007/s13346-025-01870-4","url":null,"abstract":"<p><p>Inflammation and impaired bone regeneration are major challenges in oral and maxillofacial surgery, necessitating the development of effective drug delivery systems. This study aimed to develop a hydrogel-based microneedle (MN) system for the controlled release of anti-inflammatory and osteogenic drugs. A hydrogel loaded with naproxen sodium (NAS) and dexamethasone sodium phosphate (DEX) using poloxamer 407 (NDgel) was prepared using a low-temperature method and optimized via the Box-Behnken design. The optimized hydrogel exhibited a gelation temperature of 30.87 ± 0.64℃, pH 7.92 ± 0.12, and viscosity 87.47 ± 5.66 cP. Physicochemical evaluations, including differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), confirmed that NAS and DEX were incorporated in an amorphous form. The hydrogel was coated onto microneedles (NDgMN) via a dip-coating method and dried. In vitro drug release studies in artificial saliva showed NAS and DEX release rates of 21.7 ± 5.8% and 19.0 ± 1.8%, respectively, after 5 min. The NDgMN exhibited significantly enhanced permeability, with 48.5% and 48.7% permeability for NAS and DEX after 48 h, compared to 31.0% and 28.8% for the hydrogel alone. The IC₅₀ values of the drug solution and drug-containing gel were 123 µg/mL and 203.2 µg/mL, respectively. NDgel demonstrated concentration-dependent inhibition of nitrogen oxide (NO) production at 1-1000 µg/mL, and alkaline phosphatase (ALP) activity assays revealed a 1.2-fold increase at concentrations above 50 µg/mL. These findings suggest that hydrogel-coated MNs have potential as a novel drug delivery system for reducing inflammation and promoting osteocyte differentiation due to their enhanced permeability and bioactivity.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976694","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}