Drug Delivery and Translational Research最新文献

{"title":"Mathematical modelling of hollow microneedle-mediated transdermal drug delivery.","authors":"Neil Benbrook, Wenbo Zhan","doi":"10.1007/s13346-025-01801-3","DOIUrl":"10.1007/s13346-025-01801-3","url":null,"abstract":"<p><p>Hollow microneedles represent a promising approach for overcoming the protective barrier of the stratum corneum, facilitating direct drug infusion into viable skin tissue and thereby enhancing the efficacy of transdermal delivery. However, delivery outcomes across different skin layers and into the systemic circulation can vary substantially due to the diverse properties of drug delivery systems, clinical settings, and environmental factors. The optimal strategies for enhancing the efficiency of hollow microneedle-mediated transdermal drug delivery remain to be elucidated. This study employs mathematical modelling and a reconstructed skin model with realistic anatomical structures to investigate drug transport and accumulation across different skin layers and into the bloodstream under different delivery conditions. The modelling results reveal the crucial role of interstitial fluid flow in determining drug transport in this transdermal delivery. Delivery outcomes of each skin layer and blood exhibit distinct responses to changes in delivery conditions. Specifically, increasing the vascular permeability or nanocarrier diffusivity raises drug concentration in the blood or reticular dermis, respectively, while leading to reductions in other skin layers. The use of microneedles with narrower infusion channels can only enhance drug availability in the viable epidermis. Optimisation requires a tailored approach to several parameters depending on the target skin layer, including drug release rate, infusion rate, infusion duration, and microneedle length. Environmental factors that promote trans-epidermal water loss can increase drug concentration in the viable epidermis but have a limited impact on deeper skin tissues. The findings support the selection or customisation of hollow microneedles and nanocarriers to address specific therapeutic needs, such as targeting specific skin layers or systemic circulation, while minimising the risk of side effects from high drug concentrations in normal tissues. This study provides guidance for optimising transdermal drug delivery systems.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3226-3251"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle-targeting LNP vaccines enable potent immune responses against varicella zoster virus.","authors":"Honglei Zhang, Jingxuan Ma, Lijie Jin, Yuqing Ma, Kai Dong, Jing Li, Fei Yu, Gengshen Song","doi":"10.1007/s13346-025-01961-2","DOIUrl":"https://doi.org/10.1007/s13346-025-01961-2","url":null,"abstract":"<p><p>Messenger RNA (mRNA) therapeutics have shown considerable promise across a wide range of medical applications with lipid nanoparticles (LNPs) emerging as the most clinically advanced mRNA delivery vehicles. However, the risk of off-target tissue delivery remains a concern, underscoring the need for diverse ionizable lipids to optimize LNP-based delivery systems. In this study, we designed and synthesized a library of 21 novel ionizable lipids and evaluated their potential for mRNA delivery. The resulting LNPs displayed favorable physicochemical properties and low cytotoxicity. In vitro transfection assay identified 3 high efficiency LNPs: YK-305, YK-310 and YK-319. In a mouse model, intramuscular injection of firefly luciferase (Fluc) mRNA-LNPs resulted in high transfection efficiency in muscle tissue, with significantly reduced gene expression in the liver. After encapsulating varicella zoster virus (VZV) glycoprotein E (gE)-encoding mRNA, the three LNP formulations induced robust humoral and cellular immune responses specific to the gE antigen, demonstrated improved selectivity and immunogenicity compared to SM-102, the ionizable lipid used in Moderna's Spikevax. The safety of the gE-mRNA LNP formulations were subsequently demonstrated in a mouse model. Collectively, these findings provide a foundation for the optimization of tissue-targeting ionizable lipids and highlight their potential to advance mRNA-based vaccines in clinical applications.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946386","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":"Colon delivery of agomelatine nanoparticles in the treatment of TNBS induced ulcerative colitis.","authors":"Parinaz Minaiyan, Jaleh Varshosaz, Mohsen Minaiyan","doi":"10.1007/s13346-025-01794-z","DOIUrl":"10.1007/s13346-025-01794-z","url":null,"abstract":"<p><p>Agomelatine is an atypical antidepressant with a long half-life and the mechanism of action similar to melatonin. Agomelatine is a strong antioxidant and its anti-inflammatory effect has been reported in many studies. The current study aimed to evaluate the anti-inflammatory effect of agomelatine loaded in targeted nanoparticles (NPs) in an experimental colitis model induced by trinitrobenzene sulfonic acid (TNBS). Poly(1-vinylpyrrolidone)-graft-(1-triacontene) (PVP-TA) and Eudragit^®-FS30D polymers were used alone and in combination as time, pH and time/pH dependent formulations respectively. The optimal formula was selected according to their physicochemical properties such as particle size, morphology, and drug release pattern. Six separate groups of rats were induced with 0.5 ml of TNBS. The designed groups were: normal, untreated, agomelatine (25 mg/kg/d), agomelatine/ Eudragit^®-FS30D NPs, agomelatine/ Eudragit-FS30D/PVP-TA NPs, and dexamethasone (Dex., 1 mg/kg/d). Twenty-four hours after the last administration, colonic tissue was analyzed for macroscopic and histopathological evaluations, along with quantification of malondialdehyde (MDA) and myeloperoxidase (MPO) levels. The results showed that the PVP-TA NPs alone was not suitable regarding to release profile and particle size distribution. However, Eudragit-FS30D NPs alone and Eudragit-FS30D + PVP-TA NPs passed physicochemical evaluations and were both effective in reducing the symptoms and indices of experimental colitis. Taken together, targeted NPs of agomelatine are potentially effective in treatment of ulcerative colitis.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3137-3148"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037585","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":"Biodegradable polymeric microsphere formulations of full-length anti-VEGF antibody bevacizumab for sustained intraocular delivery.","authors":"Shwetha Iyer, Cameron Lee, Mansoor M Amiji","doi":"10.1007/s13346-025-01795-y","DOIUrl":"10.1007/s13346-025-01795-y","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is one of the leading causes of central vision loss in the elderly population. Bevacizumab, a full-length humanized monoclonal anti-VEGF antibody, is commonly used off-label drug to treat AMD. However, the dosing regimen of bevacizumab and other anti-VEGF antibodies requires monthly intravitreal injections followed by regular intravitreal injections at 4-16-week intervals. In 2021, the FDA approved an innovative port delivery system of ranibizumab (Susvimo^®) that can be implanted intravitreally to slowly release the active ingredient anti-VEGF antibody and reduce injection frequency to once every 6 months. An approach utilizing polymeric slow-release microspheres encapsulating a full-length antibody, such as bevacizumab, would be much more patient-friendly because it could be injected intravitreally, avoiding surgical implantation. While microsphere encapsulation is traditionally successful for small molecule hydrophobic drugs, we assessed two different polymers, namely poly(D, L-lactide-co-glycolide) (PLGA) and poly(epsilon-caprolactone) (PCL) and discovered the benefits of utilizing a slow degrading hydrophobic polymer such as PCL for large protein therapeutic. Using the traditional double emulsion fabrication method with PCL polymer, we could produce microspheres that encapsulate bevacizumab antibody and demonstrate the release of biologically active therapeutic agent for up to 60 days. This novel approach could lead to significant advancements in our field and potentially open new avenues for future research.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3149-3160"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of product quality attributes on in vivo performance of bupivacaine multivesicular liposomes.","authors":"Ziyun Xia, Yayuan Liu, Ziyi Lu, Jingyao Gan, Minzhi Yu, Karl Olsen, Yan Wang, Xiaoming Xu, Steve Schwendeman, Anna Schwendeman","doi":"10.1007/s13346-025-01806-y","DOIUrl":"10.1007/s13346-025-01806-y","url":null,"abstract":"<p><p>A bupivacaine multivesicular liposomal injectable formulation, Exparel™, is a nonopioid long-acting local analgesic indicated for pain management across and/or post surgeries. For such products, preclinical data is lacking to support bioequivalence determination for potential generic products. Therefore, in the present work, in vivo studies were set up in male Sprague-Dawley rats to understand the in vivo performance of bupivacaine multivesicular liposomes (MVLs), aiming to provide information on bioequivalence establishment between comparator products. Bupivacaine MVLs show a multiphasic release profile, and their pharmacokinetics (PK) may differ with different experimental conditions including doses, administration routes, and sample dilution factors. In this work, compromised bupivacaine MVLs were either generated in lab by freeze-thawing, mechanical agitation, and high-temperature incubation, or chosen from years-old expired batches of Exparel™, for a preliminary investigation on the in vitro and in vivo association. The formulation attributes of different bupivacaine MVLs were characterized, including morphology, particle size distribution, formulation pH, free drug contents, in vitro release, and in vivo PK. In the rat study, even with an observation of inter- and intra-variability in PK, an association between product attributes and in vivo behaviors was demonstrated with bupivacaine MVLs. Overall, investigating the bupivacaine MVLs in vivo is beneficial not only to fill in gaps in preclinical data in the field of bupivacaine MVLs, but also to help pave the path for developing other MVL-related products.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3268-3280"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540554","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":"Mesoporous silica nanoparticles with an azobenzene gatekeeper as hypoxia-responsive nanocarriers for targeted doxorubicin delivery.","authors":"Paula Rodrigo-Martínez, Mariana Barros, María Carmen Terencio, Eva Garrido, Pau Arroyo, Jose A Sáez, Margarita Parra, Pablo Gaviña","doi":"10.1007/s13346-025-01950-5","DOIUrl":"https://doi.org/10.1007/s13346-025-01950-5","url":null,"abstract":"<p><p>Hypoxia is a key feature of solid tumors, contributing to therapeutic resistance and poor prognosis. Targeting hypoxic environments presents an opportunity to enhance drug delivery selectivity and improve treatment outcomes. Among nanocarriers, mesoporous silica nanoparticles (MSNs) have demonstrated great potential for drug delivery; however, achieving precise control over drug release remains a challenge. In this work, we develop an enzyme-responsive MSN system for targeted drug delivery in hypoxic tumors. MSNs were loaded with the chemotherapeutic drug doxorubicin (Dox) and capped with an azobenzene (Azo) gatekeeper. The bulky Azo group acts as a responsive molecular gate that remains closed under normoxic conditions but undergoes enzymatic cleavage by azoreductases, which are overexpressed in hypoxic tumor microenvironment. This cleavage triggers the uncapping of the pores, inducing the release of Dox specifically in the hypoxic region, minimizing premature drug leakage and off-target toxicity. In vitro studies with A549 cells (which overexpress azoreductase) and THP-1 cells (with low expression of azoreductases) under normoxic and hypoxic conditions, demonstrated a significant increase in Dox release and cytotoxicity in the A549 cells compared with the THP-1, which was more pronounced under hypoxia. These findings highlight the potential of enzyme-responsive MSNs as a promising strategy for selective drug delivery in hypoxic tumors.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946798","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":"Microneedle-mediated delivery of hydroxypropyl-β-cyclodextrin-encapsulated Angelica sinensis (Danggui) essential oil for acne treatment: efficacy and mechanisms.","authors":"Xiaoli Liu, Xiaojuan Li, Weijun He, Xiaoyu Han, Ting Xiao, Shiqi Guo, Yujie Jia, Liqun Lin, Ming Yang, Li Wang, Yuehong Xu","doi":"10.1007/s13346-025-01953-2","DOIUrl":"https://doi.org/10.1007/s13346-025-01953-2","url":null,"abstract":"<p><p>Acne is a multifactorial dermatological condition driven by Propionibacterium acnes (P. acnes) infection, inflammation, and sebum dysregulation. While essential oils, such as Angelica sinensis (Danggui) essential oil (AEO), exhibit antimicrobial and anti-inflammatory properties, their clinical application is hindered by poor solubility, stability, and skin penetration. To address these limitations, we developed hydroxypropyl-β-cyclodextrin (HPCD)-complexed AEO-loaded microneedles (AEO@HPCD MNs) using hyaluronic acid for enhanced transdermal delivery. The optimized AEO@HPCD MNs demonstrated superior mechanical strength, rapid dissolution, and efficient cargo release. In vitro studies confirmed potent antibacterial activity against P. acnes, while in vivo experiments revealed significant reductions in acne lesion size and IL-1β levels. RNA sequencing of treated acne lesions identified key downregulated genes (Fpr1, Rarres2, Cxcl5, Gbp3, Hck, Gbp7, Librb4a, Psmb8) and enriched pathways, including innate immunity and inflammatory responses. Notably, AEO@HPCD MNs suppressed 5α-reductase and fatty acid synthase (FAS) expression, demonstrating-for the first time-AEO's ability to normalize sebum production. Mechanistically, AEO@HPCD MNs exert multifaceted therapeutic effects: (1) direct antibacterial activity against P. acnes, (2) suppression of inflammatory and immune-related pathways through modulation of Toll-like receptor, NOD-like receptor, and cytokine-cytokine receptor signaling pathways, (3) regulation of sebum production via lipid-metabolic gene expression modulation, and (4) enhanced delivery efficiency and microenvironment modification through the physical action of microneedles, collectively contributing to synergistic acne therapy. This study develops a microneedle delivery platform that addresses both essential oil instability and inclusion complex delivery challenges while targeting multiple acne pathogenic factors. The AEO@HPCD MNs provide a safe, minimally invasive, multifunctional therapeutic strategy for acne treatment.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946854","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":"Oral colon-targeted paeonol emulsion for ameliorating ulcerative colitis based on charge adsorption.","authors":"Lan Zhang, Xi Xiong, Weiwen Lu, Jiazheng Li, Ruotong Zhang, Zhipeng Cai, Huixia Lv, Zhenhai Zhang, Jianming Ju, Ye Yang","doi":"10.1007/s13346-025-01918-5","DOIUrl":"https://doi.org/10.1007/s13346-025-01918-5","url":null,"abstract":"<p><p>Ulcerative colitis (UC), an inflammatory bowel disease, poses a severe threat to human health. Paeonol has demonstrated potential for the treatment of UC, particularly because of its remarkable anti-inflammatory properties. However, the high volatility and low oral bioavailability of paeonol hinder its application in the treatment of UC. To address this challenge, a paeonol emulsion (PEM)-based oral delivery system was developed for the treatment of UC. In this study, we investigated the colonic-targeting efficacy of PEM and the mechanisms underlying its ability to alleviate colitis. The results revealed that the negatively charged PEM specifically adhered to the positively charged inflamed colonic tissues via electrostatic interactions, enabling effective targeted delivery. Additionally, the PEM maintained the balance between M1 and M2 macrophages, exhibiting excellent efficacy in alleviating UC. Mechanistic studies have shown that PEM significantly inhibits the expression of inflammatory cytokines and repairs the intestinal barrier. Furthermore, PEM modulates the composition of the gut microbiota by inhibiting the growth of harmful bacteria and promoting the growth of beneficial bacteria. In conclusion, the negatively charged emulsion delivery system constructed provides new insights into the development of an oral colon-targeted drug delivery system.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946442","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":"Phyto-assisted synthesized CuO NPs embedded in crosslinked zein/alginate composite films for hastening wound healing and tissue regeneration in rats bio-template.","authors":"Sarah A El-Lakany, Nazik A Elgindy, Elbadawy A Kamoun, Perusi M Masanga, Shahira H El-Moslamy, Marwa Abu-Serie, Rania G Aly, Noha Khalifa Abo Aasy","doi":"10.1007/s13346-025-01948-z","DOIUrl":"https://doi.org/10.1007/s13346-025-01948-z","url":null,"abstract":"<p><p>Biopolymer-based composite films were primed by incorporating alginate and zein natural polymers using a solution-casting method and superbly assisted by eco-friendly prepared copper oxide nanoparticles (CuO NPs). The influence of the addition method of CaCl₂ as a crosslinker and CuO NPs loading content (0.1, 0.2, and 0.4 wt%) on the microstructural, physical, and mechanical properties of the films, were appraised. The formation of composite films and incorporation of CuO NPs were verified by FT-IR and XRD studies. The results unearthed that double crosslinking (Dipping method) succeeded in forming a firm, homogenous film that maintains its integrity in water for up to 24 h in comparison to the single (Blending) method. Inclusion of zein in the film and further loading with CuO NPs are manifested in a significant decrease in water vapor permeability, swelling and degradation percentage about (58.57, 52.26, and 25.80%); respectively. In addition to 1.26-folds increase in the tensile strength and 1.19-folds decrease in elongation to break, endorsing the excellent barrier property and durability of the formed films. Nevertheless, CuO loaded composite film proposes high biocompatibility against HBF4 cells with the highest IC50 and EC100 values, compared to alginate film and free-CuO NPs. The composite film exhibited the most effective antimicrobial activity against extremely drug-resistant human pathogens of both Gram-ve and Gram + ve bacteria strains, as well as fungal cells. The healed diabetic wound demonstrated an intact fully thickened keratinized epidermal epithelialization, and a complete absence of any inflammatory infiltrate after 13 days of treatment, emphasizing its suitability as a promising dressing candidate for skin tissue bioengineering.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946488","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":"Neratinib-loaded solid lipid nanoparticles in dissolvable microneedles for enhanced transdermal breast cancer therapy.","authors":"Saraisam Kishor Kumar Singha, Venkatesh Dinnekere Puttegowda, Yousef Al-Ebini, Mohamed Rahamathulla, Joysa Ruby Joseph, Ajay Pankajbhai Lunagariya, Mohammed Jafar, Syeda Ayesha Farhana, Manjunatha Panduranga Mudughal, Gowdru Vishwanath Nahusha, Mohammed Muqtader Ahmed","doi":"10.1007/s13346-025-01962-1","DOIUrl":"10.1007/s13346-025-01962-1","url":null,"abstract":"<p><p>Neratinib, an FDA-approved drug for breast cancer, faces challenges such as poor solubility, limited permeability, and adverse side effects. To address these issues, we developed dissolving microneedles incorporating Neratinib-loaded solid lipid nanoparticles (SLNs) to enhance transdermal delivery and minimize systemic toxicity. SLNs were formulated via hot homogenization using glyceryl monostearate as the lipid matrix and were evaluated for particle size, drug entrapment efficiency, drug loading, and stability. The optimized formulation (F7) exhibited a particle size of 209.4 nm and 87.57% entrapment efficiency. SLNs were integrated into microneedles using a micro-molding technique. Characterization included IR spectroscopy, scanning electron microscopy, mechanical strength, and insertion ability. Ex vivo studies on porcine skin demonstrated 80.71 ± 1.43% cumulative drug release over 24 h, confirming effective skin penetration. In vitro cytotoxicity on MCF-7 breast cancer cells showed greater efficacy of the SLN formulation over free Neratinib, with lower IC50 values (55.965 vs. 66.568 µg/mL), indicating enhanced cellular uptake and sustained release. The findings support dissolvable microneedles loaded with Neratinib-SLNs as a promising transdermal approach for targeted breast cancer therapy, offering improved bioavailability, reduced side effects, and better patient compliance.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946452","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}