Spatiotemporal fate of nanocarriers-embedded dissolving microneedles: the impact of needle dissolving rate.

OBJECTIVE: Dissolving microneedles (DMNs) have shown great potential for transdermal drug delivery due to their excellent skin-penetrating ability, and combination with nanocarriers (NCs) can realize targeted drug delivery. The objective of this study was to investigate the impact of microneedle dissolving rate on the in vivo fate of NC-loaded DMNs, which would facilitate the clinical translation of such systems. METHODS: Solid lipid nanoparticles (SLNs) were selected as the model NC for loading in DMNs, which were labeled by P4 probes with aggregation-quenching properties. Sodium hyaluronate acid (HA) and chitosan (CS), with different aqueous dissolving rates, were chosen as model tip materials. The effects of needle dissolving rate on the in vivo fate of NC-loaded DMNs was investigated by tracking the distribution of fluorescence signals after transdermal exposure. RESULTS: P4 SLNs achieved a deeper diffusion depth of 180 µm in DMN-HA with a faster dissolution rate, while the diffusion depth in DMN-CS with a slower dissolution rate was lower (140 µm). In vivo experiments demonstrated that P4 SLNs had a T1/2 value of 12.14 h in DMN-HA, whilst a longer retention time was found in DMN-CS, with a T1/2 of 13.12 h. CONCLUSIONS: This study confirmed that the in vivo diffusion rate of NC-loaded DMNs was determined by the dissolving rate of DMNs materials, and provided valuable guidance for the design and development of NC-loaded DMNs in the future.

Transdermal delivery of resveratrol loaded solid lipid nanoparticle as a microneedle patch: a novel approach for the treatment of Parkinson's disease.

Parkinson's disease (PD), affecting millions of people worldwide and expected to impact 10 million by 2030, manifests a spectrum of motor and non-motor symptoms linked to the decline of dopaminergic neurons. Current therapies manage PD symptoms but lack efficacy in slowing disease progression, emphasizing the urgency for more effective treatments. Resveratrol (RSV), recognized for its neuroprotective and antioxidative properties, encounters challenges in clinical use for PD due to limited bioavailability. Researchers have investigated lipid-based nanoformulations, specifically solid lipid nanoparticles (SLNs), to enhance RSV stability. Oral drug delivery via SLNs faces obstacles, prompting exploration into transdermal delivery using SLNs integrated with microneedles (MNs) for improved patient compliance. In this study, an RSV-loaded SLNs (RSV -SLNs) incorporated into the MN patch was developed for transdermal RSV delivery to improve its stability and patient compliance. Characterization studies demonstrated favorable physical properties of SLNs with a sustained drug release profile of 78.36 ± 0.74%. The developed MNs exhibited mechanical robustness and skin penetration capabilities. Ex vivo permeation studies displayed substantial drug permeation of 68.39 ± 1.4% through the skin. In an in vivo pharmacokinetic study, the RSV-SLNs delivered through MNs exhibited a significant increase in Cmax, Tmax, and AUC0 - t values, alongside a reduced elimination rate in blood plasma in contrast to the administration of pure RSV via MNs. Moreover, an in vivo study showcased enhanced behavioral functioning and increased brain antioxidant levels in the treated animals. In-vivo skin irritation study revealed no signs of irritation till 24 h which permits long-term MNs application. Histopathological analysis showed notable changes in the brain regions of the rat, specifically the striatum and substantia nigra, after the completion of the treatment. Based on these findings, the development of an RSV-SLN loaded MNs (RSVSNLMP) patch presents a novel approach, with the potential to enhance the drug's efficiency, patient compliance, and therapeutic outcomes for PD, offering a promising avenue for advanced PD therapy.

Simulated skin model for in vitro evaluation of insertion performance of microneedles: design, development, and application verification.

Microneedles, as a new efficient and safe transdermal drug delivery technology, has a wide range of applications in drug delivery, vaccination, medical cosmetology, and diagnostics. The degree of microneedles penetration into the skin determines the reliability of the delivery dose, but its evaluation is not yet well-established, which is one of the major constraints in the commercialization of microneedles. In this paper, a novel visual simulated skin model was developed with reference to the physical properties of real skin. The simulated skin model was well-designed and its prescription was optimized to make the thickness, hardness, elasticity, and other parameters close to those of real skin. It not only meets the need to assess the degree of insertion of microneedles but also provides a visual observation of the insertion state of microneedles.

Transdermal microneedle patches as a promising drug delivery system for anti-obesogenic molecules.

Obesity, characterized by excessive storage of lipids, has become a global pandemic with high incidence levels, and its forecast is not encouraging. Currently, there are different strategies to treat obesity; however, these conventional methods have various limitations. Lifestyle changes may result in poor outcomes due to the complexity of obesity causes, pharmaceutic treatments produce severe side effects, and bariatric surgery is highly invasive. In the search for alternative treatments to fight obesity, transdermal drug delivery systems of anti-obesogenic molecules have gained particular attention. However, the diffusion of molecules through the skin is the main drawback due to the characteristics of different layers of the skin, principally the stratum corneum and its barrier-like behavior. In this sense, microneedles patches (MP) have emerged to overcome this limitation by piercing the skin and allowing drug delivery inside the body. Although MP have been studied for some years, it was not until about 2017 that their potential as anti-obesogenic treatment was reported. This article aims to summarize and analyze the strategies employed to produce MP and to embed the active molecules against obesity. Special attention is focused on the microneedle's material, geometry, array, and additional delivery strategies, like nanoencapsulation. MP are a promising tool to develop an easy-access treatment, avoiding the digestive tract and with the capacity to enhance the anti-obesogenic activity by delivering one or more active molecules.

Corn-inspired high-density plasmonic metal-organic frameworks microneedles for enhanced SERS detection of acetaminophen.

Effective monitoring of acetaminophen (APAP) dosage is crucial for preventing antipyretic abuse, ensuring therapeutic efficacy, and minimizing toxic effects. However, existing self-monitoring methods are limited. In this study, we designed a plasmonic microneedle (MN) sensor for real-time nondestructive monitoring of acetaminophen levels in dermal interstitial fluid (ISF) by employing a handheld Raman spectrometer. The fabricated MN sensor incorporated a high-density plasmonic MOFs known as HDPM, which unique structure of large specific surface area, specific pore structure as well as high density gold nanospheres packing enabled the excellent performance of selective ISF drug enrichment and surface-enhanced Raman scattering (SERS). The maximum electric field enhancement factor of the HDPM nanostructure could be calculated as 5.73 × 107. The developed HDPM@MNs was characterized with a core-shell type "soft on the outside and rigid on the inside" structure, which exhibited sufficient hardness and flexibility to penetrate the dermal tissue with little damage, and robust SERS enhancement effect in APAP detection without any interfering peaks. Through a hydrogel drug simulation experiment, the sensor demonstrated robust capabilities for acetaminophen enrichment and monitoring, exhibiting excellent stability and repeatability. The quantitative detection window spanned from 1 to 100 µM, with a low detection limit reaching 0.45 µM. Furthermore, by monitoring the concentration of acetaminophen in the interstitial fluid of rat skin at different doses and for different administration times, the HDPM@MNs can be used to determine the pharmacokinetics of acetaminophen in rats and the physiological characteristics associated with various dosage regimens. This work not only holds promise for drug monitoring but also provides a novel approach for nondestructive monitoring of other crucial low-abundance physiological markers.

Emerging innovations in portable chemical sensing devices: Advancements from microneedles to hydrogel, microfluidic, and paper-based platforms.

With the public heightened emphasis on mitigating the occurrence risks of health-related ailment and optimizing personal physical performance, portable chemical sensing devices emerged as an indispensable component of pervasive health monitoring. Chemical sensing enabled the immediate and on-site identification of biomarkers in biological fluids by integrating colorimetry, fluorescence, electrochemical, and other methods into portable sensor devices. These sensor devices incorporated microneedles, hydrogels, microfluidic modules, and papers, facilitating conformal human-device contact and providing several visual sensing options for disease prevention and healthcare management. This review systematically overviewed recent advancements in chemical sensors for marker detection, categorizing them based on monitoring device types. Furthermore, we also offered recommendations and opportunities for developing portable chemical sensing devices by summarizing sensor integration methods and tracking sites on the human body.

Swellable Microneedles in Drug Delivery and Diagnostics.

This manuscript explores the transformative potential of swellable microneedles (MNs) in drug delivery and diagnostics, addressing critical needs in medical treatment and monitoring. Innovations in hydrogel-integrated MN arrays facilitate controlled drug release, thereby expanding treatment options for chronic diseases and conditions that require precise dosage control. The review covers challenges, such as scalability, patient compliance, and manufacturing processes, as well as achievements in advanced manufacturing, biocompatibility, and versatile applications. Nonetheless, limitations in physiological responsiveness and long-term stability remain, necessitating further research in material innovation and integration with digital technologies. Future directions focus on expanding biomedical applications, material advancements, and regulatory considerations for widespread clinical adoption.

Improvement of lidocaine skin permeation by using passive and active enhancer methods.

Lidocaine is generally recognized and preferred for local anaesthesia, but in addition, studies have described additional benefits of lidocaine in cancer therapy, inflammation reduction, and wound healing. These properties contribute to its increasing importance in dermatological applications, and not only in pain relief but also in other potential therapeutic outcomes. Therefore, the purpose of our study was to enhance lidocaine delivery through the skin. A stable nanostructured lipid carrier (NLC), as a passive permeation enhancer, was developed using a 23 full factorial design. The nanosystems were characterized by crystallinity behaviour, particle size, zeta potential, encapsulation efficiency measurements, and one of them was selected for further investigation. Then, NLC gel was formulated for dermal application and compared to a traditional dermal ointment in terms of physicochemical (rheological behaviour) and biopharmaceutical (qualitative Franz diffusion and quantitative Raman investigations) properties. The study also examined the use of 3D printed solid microneedles as active permeation enhancers for these systems, offering a minimally invasive approach to enhance transdermal drug delivery. By actively facilitating drug permeation through the skin, microneedles can complement the passive transport achieved by NLCs, thereby providing an innovative and synergistic approach to improving lidocaine delivery.

Combined photodynamic therapy and hollow microneedle approach for effective non-invasive delivery of hypericin for the management of imiquimod-induced psoriasis.

BACKGROUND: Conventional topical psoriasis treatments suffer from limited delivery to affected areas and skin irritation due to high local drug concentration. PURPOSE: This study aims to prepare hypericin (HYP) loaded nanostructured lipid carriers (NLCs) and their application in psoriasis treatment through intradermal administration using hollow microneedles assisted by photodynamic therapy. METHODS: The colloidal characteristics of NLCs, entrapment efficiency and morphology were evaluated. An ex-vivo skin distribution study was conducted along with testing the in vivo antipsoriatic activity in mice with the imiquimod-induced psoriasis model. RESULTS: The particle size and zeta potential of HYP-NLCs were 167.70 nm and -18.1, respectively. The ex-vivo skin distribution study demonstrated the superior distribution of HYP-NLCs to a depth of 1480 µm within the skin layers relative to only 750 µm for free HYP. In vivo studies revealed that the levels of NF-KB, IL 6, MMP1, GSH, and catalase in the group treated with HYP-NLCs in the presence of light were comparable to the negative control. CONCLUSIONS: The histopathological inspection of dissected skin samples reflected the superiority of HYP-NLCs over HYP ointment. This could be ascribed to the effect of nanoencapsulation on improving HYP properties besides the ability of hollow microneedles to ensure effective HYP delivery to the affected psoriatic area.

Multifunctional Dopamine-Based Hydrogel Microneedle Electrode for Continuous Ketone Sensing.

Diabetic ketoacidosis (DKA), a severe complication of type 1 diabetes (T1D), is triggered by production of large quantities of ketone bodies, requiring patients with T1D to constantly monitor their ketone levels. Here, a skin-compatible hydrogel microneedle (HMN)-continuous ketone monitoring (HMN-CKM) device is reported. The sensing mechanism relies on the catechol-quinone chemistry inherent to the dopamine (DA) molecules that are covalently linked to the polymer structure of the HMN patch. The DA serves the dual-purpose of acting as a redox mediator for measuring the byproduct of oxidation of 3-beta-hydroxybutyrate (ß-HB), the primary ketone bodies; while, also facilitating the formation of a crosslinked HMN patch. A universal approach involving pre-oxidation and detection of the generated catechol compounds is introduced to correlate the sensor response to the ß-HB concentrations. It is further shown that real-time tracking of a decrease in ketone levels of T1D rat model is possible using the HMN-CKM device, in conjunction with a data-driven machine learning model that considers potential time delays.

The potential of RNA therapeutics in dermatology.

Ribonucleic acid (RNA) therapeutics hold great potential for the advancement of dermatological treatments due to, among other reasons, the possibility of treating previously undruggable targets, high specificity with minimal side effects, and ability to include multiple RNA targets in a single product. Although there have been research relating to RNA therapeutics for decades, there have not been many products translated for clinical use until recently. This may be because of challenges to the application of RNA therapeutics, including the dearth of effective modes of delivery to the target, and rapid degradation of RNA in the human body and environment. This article aims to provide insight on (1) the wide-ranging possibilities of RNA therapeutics in the field of dermatology as well as (2) how key challenges can be addressed, so as to encourage the development of novel dermatological treatments. We also share our experience on how RNA therapeutics have been applied in the management of hypertrophic and keloid scars.

Spiderweb-Shaped Iron-Coordinated Polymeric Network as the Novel Coating on Microneedles for Transdermal Drug Delivery Against Infectious Wounds.

Coated microneedles (CMNs) are a minimally invasive platform for immediate-release transdermal drug delivery. However, the practical applications of CMNs have been significantly hindered by the challenges associated with complex formulations, single function, and limited drug loading capacity. In this study, we have developed a spiderweb-shaped iron-coordinated polymeric nanowire network (Fe-IDA NWs). The resulting Fe-IDA NWs are endowed with a certain viscosity due to the synergy of multiple supramolecular interactions. This allows them to replace traditional polymeric thickeners as microneedle coatings. The Fe-IDA NWs-coated microneedles (Fe-IDA MNs) display rapid disintegration in the skin model, which also enables the swift diffusion of Fe-IDA NWs and their payloads into the deeper skin layers. Additionally, Fe-IDA MNs exhibit desirable enzymatic activity and potential antibacterial ability. Thus, Fe-IDA MNs can enhance the therapeutic efficacy against wound infection through synergistic effects, and avoid the overly complicated formulation and the release of non-therapeutic molecules of conventional CMNs. As a proof-of-concept, Fe-IDA MNs loaded with chlorin e6 showed a synergistic chemodynamic-photodynamic antibacterial effect in a methicillin-resistant Staphylococcus aureus-infected wound model in mice. Collectively, this work has significant implications for the future of CMNs-based transdermal drug delivery systems and expands the application fields of metal coordination polymer materials. This article is protected by copyright. All rights reserved.

Semi-invasive wearable clinic: Solution-processed smart microneedle electronics for next-generation integrated diagnosis and treatment.

The integrated smart electronics for real-time monitoring and personalized therapy of disease-related analytes have been gradually gaining tremendous attention. However, human tissue barriers, including the skin barrier and brain-blood barrier, pose significant challenges for effective biomarker detection and drug delivery. Microneedle (MN) electronics present a promising solution to overcome these tissue barriers due to their semi-invasive structures, enabling effective drug delivery and target-analyte detection without compromising the tissue configuration. Furthermore, MNs can be fabricated through solution processing, facilitating large-scale manufacturing. This review provides a comprehensive summary of the recent three-year advancements in smart MNs development, categorized as follows. First, the solution-processed technology for MNs is introduced, with a focus on various printing technologies. Subsequently, smart MNs designed for sensing, drug delivery, and integrated systems combining diagnosis and treatment are separately summarized. Finally, the prospective and promising applications of next-generation MNs within mediated diagnosis and treatment systems are discussed.

Systemic delivery of bictegravir and tenofovir alafenamide using dissolving microneedles for HIV preexposure prophylaxis.

Human immunodeficiency virus (HIV) continues to pose a serious threat to global health. Oral preexposure prophylaxis (PrEP), considered highly effective for HIV prevention, is the utilisation of antiretroviral (ARV) drugs before HIV exposure in high-risk uninfected individuals. However, ARV drugs are associated with poor patient compliance and pill fatigue due to their daily oral dosing. Therefore, an alternative strategy for drug delivery is required. In this work, two dissolving microneedle patches (MNs) containing either bictegravir (BIC) or tenofovir alafenamide (TAF) solid drug nanoparticles (SDNs) were developed for systemic delivery of a novel ARV regimen for potential HIV prevention. According to ex vivo skin deposition studies, approximately 11 % and 50 % of BIC and TAF was delivered using dissolving MNs, respectively. Pharmacokinetic studies in Sprague Dawley rats demonstrated that BIC MNs achieved a long-acting release profile, maintaining the relative plasma concentration above the 95 % inhibitory concentration (IC95) for 3 weeks. For TAF MNs, a rapid release of drug and metabolism of TAF into TFV were obtained from the plasma samples. This work has shown that the proposed transdermal drug delivery platform could be potentially used as an alternative method to systemically deliver ARV drugs for HIV PrEP.

Iontophoresis-coupled rapidly dissolving polymeric microneedle patch of naloxone for its enhanced transdermal delivery.

The transdermal delivery of naloxone for opioid overdose emergency purposes is a challenge due to its poor rate of diffusion through the layers of skin. This results in delayed delivery of an insufficient amount of the drug within minimal time as is desired to save lives. The ability of dissolving polymeric microneedles to shorten the lag time significantly has been explored and shown to have prospects in terms of the transdermal delivery of naloxone. This is an option that offers critical advantages to the ongoing opioid crisis, including ease of distribution and easy administration, with little to no need for intervention by clinicians. Nonetheless, this approach by itself needs augmentation to meet pharmacokinetic delivery attributes desired for a viable clinical alternative to existing market dosage forms. In this study, we report the success of an optimized iontophoresis-coupled naloxone loaded dissolving microneedle patch which had facilitated a 12- fold increase in average cumulative permeation and a 6-fold increase in drug flux over a conventional dissolving microneedle patch within 60 min of application (p < 0.05). This translates to a 30 % decrease in dose requirement in a mechanistically predicted microneedle patch established to be able to achieve the desired early plasma concentration time profile needed in an opioid overdose emergency. Applying a predictive mathematical model, we describe an iontophoresis-coupled microneedle patch design capable of meeting the desired pharmacokinetic profile for a viable naloxone delivery form through skin.

Reactive oxide species and ultrasound dual-responsive bilayer microneedle array for in-situ sequential therapy of acute myocardial infarction.

Acute myocardial infarction (AMI) resulting from coronary artery occlusion stands as the predominant cause of cardiovascular disability and mortality worldwide. An all-encompassing treatment strategy targeting pathological processes of oxidative stress, inflammation, proliferation and fibrotic remodeling post-AMI is anticipated to enhance therapeutic outcomes. Herein, an up-down-structured bilayer microneedle (Ce-CLMs-BMN) with reactive oxygen species (ROS) and ultrasound (US) dual-responsiveness is proposed for AMI in-situ sequential therapy. The upper-layer microneedle is formulated by crosslinking ROS-sensitive linker with polyvinyl alcohol loaded with cerium dioxide nanoparticles (CeNPs) featuring versatile enzyme-mimetic activities. During AMI acute phase, prompted by ischemia-induced microenvironmental redox imbalance, this layer swiftly releases CeNPs, which aid in eliminating excessive ROS and catalyzing oxygen gas (O2) production through multiple enzymatic pathways, thereby alleviating oxidative stress-induced damage and modulating inflammation. In AMI chronic repair phase, micro-nano reactors (CLMs) situated in the lower-layer microneedle undergo cascade reactions with the assistance of US irradiation to generate nitric oxide (NO). As a bioactive molecule with pro-angiogenic and anti-fibrotic effects, NO expedites cardiac repair while attenuating adverse remodeling. Additionally, its antiplatelet-aggregating properties contribute to thromboprophylaxis. In-vitro and in-vivo results substantiate the efficacy of this integrated healing approach in AMI management, showcasing promising prospects for advancing infarcted heart repair.

Recent advances in transdermal insulin delivery technology: A review.

Transdermal drug delivery refers to the administration of drugs through the skin, after which the drugs can directly act on or circulate through the body to the target organs or cells and avoid the first-pass metabolism in the liver and kidneys experienced by oral drugs, reducing the risk of drug poisoning. From the initial singular approach to transdermal drug delivery, there has been a shift toward combining multiple methods to enhance drug permeation efficiency and address the limitations of individual approaches. Technological advancements have also improved the accuracy of drug delivery. Optimizing insulin itself also enables its long-term release via needle-free injectors. In this review, the diverse transdermal delivery methods employed in insulin therapy and their respective advantages and limitations are discussed. By considering factors such as the principles of transdermal penetration, drug delivery efficiency, research progress, synergistic innovations among different methods, patient compliance, skin damage, and posttreatment skin recovery, a comprehensive evaluation is presented, along with prospects for potential novel combinatorial approaches. Furthermore, as insulin is a macromolecular drug, insights gained from its transdermal delivery may also serve as a valuable reference for the use of other macromolecular drugs for treatment.

Development of ropivacaine hydrochloride-loaded dissolving microneedles as a local anesthetic agent: A proof-of-concept.

Ropivacaine hydrochloride (RPL) is a local anesthetic agent that has been widely used for the treatment of pain during or after surgery. However, this drug is only available in parenteral dosage form and may contribute to the infiltration of RPL into the plasma, causing some undesirable side effects. Intradermal delivery of RPL using dissolving microneedles may become a promising strategy to deliver such drugs into the skin. This research aimed to develop RPL-loaded dissolving microneedles (DMN-RPLs) as a proof of the concept of intradermal delivery of a local anesthetic. The DMN-RPLs were fabricated using either centrifugation or air-pressurized chamber methods. Several polymers, such as poly(vinyl pyrrolidone) (PVP), poly(vinyl alcohol) (PVA), and sodium hyaluronate (SH), were utilized for manufacturing the DMN-RPLs. The prepared DMN-RPLs were assessed for their thermal properties, chemical bonds, mechanical strength, insertion ability, skin-dissolution study, and drug content. Furthermore, in-skin deposition and dermatokinetic studies were also performed. The results showed that F9 (30 % w/w PVP-4 % w/w SH) and F10 (30 % w/w PVP-5 % w/w PVA) containing 5 % w/w of RPL were the most promising formulations, as shown by their needle height reduction (<10 %) and insertion depth (∼400 µm). Both formulations were also able to deliver more than 60 % of the RPL contained in the DMNs into the epidermis, dermis, and receiver compartment. This study, for the first time, has provided a proof concept to deliver RPL as a local anesthetic using DMNs and the intradermal route, aiming to minimize pain and discomfort during administration and improve the patient's experience.

Battery-free optoelectronic patch for photodynamic and light therapies in treating bacteria-infected wounds.

Light therapy is an effective approach for the treatment of a variety of challenging dermatological conditions. In contrast to existing methods involving high doses and large areas of illumination, alternative strategies based on wearable designs that utilize a low light dose over an extended period provide a precise and convenient treatment. In this study, we present a battery-free, skin-integrated optoelectronic patch that incorporates a coil-powered circuit, an array of microscale violet and red light emitting diodes (LEDs), and polymer microneedles (MNs) loaded with 5-aminolevulinic acid (5-ALA). These polymer MNs, based on the biodegradable composite materials of polyvinyl alcohol (PVA) and hyaluronic acid (HA), serve as light waveguides for optical access and a medium for drug release into deeper skin layers. Unlike conventional clinical photomedical appliances with a rigid and fixed light source, this flexible design allows for a conformable light source that can be applied directly to the skin. In animal models with bacterial-infected wounds, the experimental group with the combination treatment of metronomic photodynamic and light therapies reduced 2.48 log10 CFU mL-1 in bactericidal level compared to the control group, indicating an effective anti-infective response. Furthermore, post-treatment analysis revealed the activation of proregenerative genes in monocyte and macrophage cell populations, suggesting enhanced tissue regeneration, neovascularization, and dermal recovery. Overall, this optoelectronic patch design broadens the scope for targeting deep skin lesions, and provides an alternative with the functionality of standard clinical light therapy methods.

Curcumin analogue AC17-loaded dissolvable microneedles activate FOXO3 and enhance localized drug delivery for oral squamous cell carcinoma treatment.

Curcumin, a polyphenol extracted from turmeric, is a potential alternative for the treatment of oral squamous cell carcinoma (OSCC) due to its remarkable anticancer activity and low systemic toxicity. To further enhance the anticancer activity and bioavailability of curcumin, we synthesized a curcumin analogue, AC17, by modifying the benzene ring and methylene group of curcumin. A soluble hyaluronic acid microneedle patch (AC17@HAMN) was developed to ensure accurate and safe delivery of AC17 to tumor tissues. The inhibitory effect of AC17 on OSCC cells was stronger than that of curcumin and some common analogues. Transcriptome sequencing showed that the target genes of AC17 were mainly concentrated in apoptosis, cell cycle and cell senescence pathways. Among them, AC17 induces cell cycle arrest and inhibits cell proliferation mainly by activating FOXO3 signaling. With good penetration and dissolution properties, microneedles can deliver AC17 directly to the tumor site and show good anti-tumor effect. Moreover, AC17@HAMN showed good biosafety. In summary, AC17@HAMN offers high efficiency, minimal invasiveness, and few adverse reactions. This microneedle patch holds great promise for potential clinical applications, especially for the treatment of OSCC.