Microneedle Arrays Research Articles

Nanoporous Plasmonic Microneedle Arrays Induced High-Efficiency Intracellular Delivery of Metabolism Regulating Protein.

Patterned micro/nanostructure arrays have shown the potential to effectively regulate cellular behavior, and their unique microstructure may address the limitations of conventional pore materials, leading to novel phenomena. In this work, a large-area gold micro/nano-array substrate with an average hole of ≈32nm is designed and extensively screened. Precisely engineered nanopores on the substrate can effectively improve photothermal conversion efficiency, and instant heat dissipation in the absence of laser irradiation. The mesoporous arrays are fabricated by hybrid lithography, offering advantages such as simple processing, high reproducibility, and immense commercial potential. Notably, its heating rate is as rapid as ≈45 Kµs-1 at low power levels, with the cooling duration reduced to ≈50 µs after the laser irradiation. Metabolism regulatory proteins such as cytochrome C (CytoC)and β-galactosidase (β-gal) can be efficiently introduced into the U87 cell model without inducing phototoxicity or protein inactivation, maintaining catalytic activity to modulate the cellular metabolic state. This delivery platform based on transient nano-cyclones stimulating cell perturbations can be further expanded through modulated microstructures, such as delivering functional proteins or biomolecules for efficient intracellular regulation, cellular transfection, and in the future application as a potential high-throughput screening tool for clustered regularly interspaced short palindromic repeats (CAR-T) biopharmaceutical and clustered regularly interspaced short palindromic repeats (CRISPR) technologies.

Fabrication and characterization of dissolving microneedles combining Digital light processing and vacuum compression molding technique for the transdermal delivery of rivastigmine.

Dissolving microneedles (MNs) are promising transdermal drug delivery systems that can effectively increase the absorption of the drugs. They bypass the first layer of the skin, the stratum corneum (SC) and deliver the drugs directly into the dermis, by dissolving inside the interstitial fluid and releasing the active. The traditional ways of MN fabrication involve primarily micromolding, which basically uses silicone molds. Drugs and polymer mixture solutions are poured into these molds and after drying the MN arrays are carefully removed. In the present study, a novel molding process was employed to fabricate dissolving MNs containing rivastigmine (RIV). RIV is available as an oral tablet and a transdermal patch. The patch (Exelon®), used for managing Alzheimer's symptoms in mild to moderate dementia, releases only about 50 % of its drug content, raising concerns about dose wastage, environmental impact, and patient costs. Thus, RIV was selected as the model drug to fabricate MNs by combining to novel processes, Digital Light Processing and Free-D Molding, a Vacuum Compression Molding (VCM) Technique provided by MeltPrep®. The developed arrays were evaluated regarding their physiochemical characteristics and their ability to penetrate the skin without breaking or creating fragments, as they can withstand forces up to 600 N. The MNs were visualized using optical microscopy, SEM, and CLSM to examine their geometry, surface and length (0.708 mm). Permeability studies verified that the MNs can increase significantly RIV transportation across the skin, up to 9-fold. Histological analysis was conducted to ensure that the produced MNs are safe for transdermal applications. Overall, the present study suggests that Free-D molding, a combination of 3D printing and VCM can produce dissolving MN arrays that are effective and safe for transdermal applications.

High-Density Microneedle Array-Based Wearable Electrochemical Biosensor for Detection of Insulin in Interstitial Fluid

The development of point-of-care wearable devices capable of measuring insulin concentration has the potential to significantly improve diabetes management and life quality of diabetic patients. However, the lack of a suitable point-of-care device for personal use makes regular insulin level measurements challenging, in stark contrast to glucose monitoring. Herein, we report an electrochemical transdermal biosensor that utilizes a high-density polymeric microneedle array (MNA) to detect insulin in interstitial fluid (ISF). The biosensor consists of gold-coated polymeric MNA modified with an insulin-selective aptamer, which was used for extraction and electrochemical quantification of the insulin in ISF. In vitro testing of biosensor, performed in artificial ISF (aISF), showed high selectivity for insulin with a linear response between 0.01 nM to 4 nM (sensitivity of ∼65 Ω nM-1), a range that covers both the physiological and the pathological concentration range. Furthermore, ex vivo extraction and quantification of insulin from mouse skin showed no impact on the biosensor's linear response. As a proof of concept, an MNA-based biosensing platform was utilized for the extraction and quantification of insulin on live mouse skin. In vivo application showed the ability of MNs to reach ISF, extract insulin from ISF, and perform electrochemical measurements sufficient for determining insulin levels in blood and ISF. We believe that our MNA-based biosensing platform based on extraction and quantification of the biomarkers will help move insulin assays from traditional laboratory approaches to personalized point-of-care settings.

Ice-pop making inspired photothermal ultra-swelling microneedles to facilitate loading and intradermal vaccination of tumor antigen.

Ice-pop making inspired photothermal ultra-swelling microneedles to facilitate loading and intradermal vaccination of tumor antigen.

Machine learning-assisted implantable plant electrophysiology microneedle sensor for plant stress monitoring.

Machine learning-assisted implantable plant electrophysiology microneedle sensor for plant stress monitoring.

Detection of cytochrome c in biofilm-material interfacial microenvironment with hydrogel microneedle array

Detection of cytochrome c in biofilm-material interfacial microenvironment with hydrogel microneedle array

Microarray patches likely to reduce the operational costs of immunization: A Monte Carlo simulation study.

Microarray patches likely to reduce the operational costs of immunization: A Monte Carlo simulation study.

Microneedle Arrays for Brain Drug Delivery: The Potential of Additive Manufacturing

For a long time, the treatment of brain diseases has been a significant challenge. Drug delivery to the brain has recently become one of the most challenging problems for patients with severe forms of central nervous system (CNS) diseases. The blood-brain barrier (BBB) poses a significant challenge for drug delivery to the brain. While extensive efforts focus on finding materials to overcome the BBB for brain tumor treatment, it limits the penetration of chemotherapeutic drugs for the broader treatment of brain diseases. The oral method of drug administration has several drawbacks, such as the loss of drugs because of metabolism and gastrointestinal environmental issues. Besides, using the intravenous route to administer medicines has several disadvantages, including discomfort at the injection site, infection, bleeding, anxiety, and incompetence toward patients. Fabrication and development of microneedles (MNs) to overcome the drawbacks mentioned above of traditional drug delivery methods may be a viable alternative. Drug delivery using microneedle arrays (MNAs) has recently been shown to be an effective method for delivering drugs to the brain. Different fabricating methods like three-dimensional (3D) printing could be used for the fabrication of personalized drug delivery systems, like MNAs, with precise control over spatiotemporal drug distribution. This article presents a review of using MNAs for drug delivery to the brain.

Pd-Modified Microneedle Array Sensor Integration with Deep Learning for Predicting Silica Aerogel Properties in Real Time.

The continuous global effort to predict material properties through artificial intelligence has predominantly focused on utilizing material stoichiometry or structures in deep learning models. This study aims to predict material properties using electrochemical impedance data, along with frequency and time parameters, that can be obtained during processing stages. The target material, silica aerogel, is widely recognized for its lightweight structure and excellent insulating properties, which are attributed to its large surface area and pore size. However, production is often delayed due to the prolonged aging process. Real-time prediction of material properties during processing can significantly enhance process optimization and monitoring. In this study, we developed a system to predict the physical properties of silica aerogel, specifically pore diameter, pore volume, and surface area. This system integrates a 3 × 3 array Pd/Au sensor, which exhibits high sensitivity to varying pH levels during aerogel synthesis and is capable of acquiring a large data set (impedance, frequency, time) in real-time. The collected data is then processed through a deep neural network algorithm. Because the system is trained with data obtained during the processing stage, it enables real-time predictions of the critical properties of silica aerogel, thus facilitating process optimization and monitoring. The final performance evaluation demonstrated an optimal alignment between true and predicted values for silica aerogel properties, with a mean absolute percentage error of approximately 0.9%. This approach holds great promise for significantly improving the efficiency and effectiveness of silica aerogel production by providing accurate real-time predictions.

Advancements in Glucose Monitoring: From Traditional Methods to Wearable Sensors

Accurate in vivo glucose monitoring is essential for effective diabetes management and for the care of pre-term infants in critical care. Glucose-monitoring techniques are broadly categorized into three types: invasive, minimally invasive, and non-invasive. Each method presents distinct advantages and challenges. Non-invasive glucose sensors, despite impressive advancements in recent years, still face issues with signal interference and accuracy, limiting their widespread clinical application. In contrast, implanted devices offer more reliable and consistent results in clinical settings, making them the current gold standard. This review provides an overview of the leading glucose-sensing technologies, detailing both their advantages and drawbacks. We discuss invasive techniques, such as implanted electrodes, which allow continuous glucose monitoring with high accuracy, but often come with risks of infection and discomfort. Minimally invasive methods, such as fluorescence sensors, Raman sensors, and microneedle arrays, aim to reduce discomfort while providing more precise measurements than non-invasive devices. Additionally, non-invasive methods, such as optical, infrared, and microwave techniques, are explored for their potential to provide pain-free, continuous glucose monitoring. Finally, the review highlights a brief comparison among the current technologies and future directions in the field, particularly the use of signal enhancement algorithms and integration with wearable devices.

Recent advances in microneedles for enhanced functional angiogenesis and vascular drug delivery.

Many therapeutic applications use the transdermal method to avoid the severe restrictions associated with oral medication delivery. Given the limitations of traditional drug delivery via skin, transdermal microneedle (MN) arrays have been reported to be versatile and very efficient devices due to their outstanding characteristics such as painless penetration, affordability, excellent medicinal efficacy, and relative safety. MNs have recently received increased attention for their ability to cure vascular illnesses such as hypertension and thrombosis, as well as promote wound healing via the angiogenesis impact. The integrant of method manufacturing and biodegradable material allows for the modification of MN form and drug release pattern, hence increasing the flexibility of such drug delivery. In this review, we focused on recent improvements in MN-mediated transdermal administration of protein and peptide medicines for improved functional angiogenesis and vascular therapy. We also provide an overview of the present applications of MNs-mediated transdermal protein and peptide administration, particularly in the realm of vascular system disease therapy. Finally, the current state of clinical translation and a forecast for future progress are provided.

MWCNTs/PANI silk fibroin film sensor based on microneedle array for sweat pH detection.

Incorporating silk fibroin (SF) into the biosensing platform provides a level of flexibility and macro-structure control that holds immense importance for monitoring of sweat pH. Itaccomplishes non-invasive surveillance of the human physiology while concurrently tackling the issue of electrode-skin friction. The preparation of the multi-walled carbon nanotubes (MWCNTs)/polyaniline (PANI) silk fibroin pH-responsive microneedle array sensor involves the dispersion of PANI powder in silk fibroin and the addition of MWCNTs for the analysis of human sweat. The template method offers an efficient and straightforward means of producing microneedles with a high degree of precision, achieving micrometerresolution. The pH sensor is designed with a two-electrode configuration, comprising an MWCNTs/PANI silk fibroin microneedle array sensing electrode as well as an Ag/AgCl reference electrode. The pH sensor shows a sensitivity of 53.60mV/pH over the pH range 3 to 9, a response time of 68s, and a recovery time of 77s. The pH sensor displays other outstanding sensor performances regarding reversibility, repeatability, selectivity, and stability. The pH sensor is capable of detecting alterations in the pH levels of human sweat.

3D-printed microneedle arrays for real-time interstitial fluid glucose monitoring

Abstract Efficient, accurate, and real-time blood glucose monitoring is crucial for diabetes management. Using interstitial fluid (ISF) instead of blood for monitoring is a key focus. However, microneedle-based in-situ methods face challenges in comfort and miniaturization. This study presents a novel wearable patch for ISF glucose monitoring. The patch features a miniature square microneedle array (MNA) connected to the substrate via microstructure, ensuring strong fixation and easy replacement. The MNA is 3D-printed, offering personalization, efficiency, low cost, and biocompatibility. Through the design of the microneedle arrangement on the array, an innovative circular array microneedle configuration is utilized to reduce insertion difficulty and enhance long-term wear comfort by reducing issues related to skin elasticity. Its surface is modified with a bonding, conductive, and functionalized layer for accurate glucose monitoring after insertion . Experimental results show the sensor's high sensitivity and selectivity for real-time ISF glucose monitoring, suitable for both healthy individuals and diabetics. The device is painless, compact, flexible, low-cost, and comfortable, with replaceable electrodes, making it promising for practical diabetes management.

Advancements in Flexible Electrode Implantation for Invasive Brain-Computer Interfaces

In recent years, with the development of flexible electronic devices and advances in material science, flexible electrodes have played an important role in the field of invasive brain-computer interface (BCI). Compared with traditional rigid electrodes, flexible electrodes implanted in the brain cause less damage to brain tissue and are more biocompatible and stable. Most of the traditional invasive electrodes are made of glass or metal, which are prone to brain tissue damage, inflammation, and other problems, although they can avoid interference from the skull and skin and record neural signals accurately and with low noise. However, the main materials for flexible electrodes are polymers, hydrogels, graphene, etc., which can reduce immune rejection and prolong the service life of neural implants. This paper describes five main implantation methods for flexible electrodes in recent years: microneedle arrays, coiled implantation, minimally invasive injections, biodegradable electrodes, and stretchable electronics implantation. They can be used in the most appropriate way for electrodes of different structures to acquire neural signals with stable and reliable fidelity. Flexible electrodes have the potential for a wide range of applications in neuromonitoring providing a safer and more durable solution for invasive brain-computer interfaces. Then the authors will propose a new idea combining their respective advantages in the hope of bringing enlightenment.

Glassy Drug Microneedle Array Design: Drug Glass-Forming Ability and Stability.

Glassy microneedles, composed only of drug, provide an intradermal alternative to oral or parenteral drug delivery. Compared to microneedles composed of drug-polymer solid dispersions, they offer higher drug loading while possessing mechanical strength for skin penetration. However, their microneedle structure and associated mechanical strength are reliant on the component glass stability. This study investigates relationships between the glass stability of drug-only microneedles and drug glass-forming ability (GFA), determined by differential scanning calorimetry (DSC) analysis. The glass stability of microneedles fabricated from six drugs was evaluated at 2-8 °C under nitrogen, 25 °C/60% relative humidity (RH), and 40 °C/75% RH. Drug glass stability was determined by visual assessment of microneedle appearance, together with DSC and powder X-ray diffraction analysis of the drug melt cooled outside the microneedle molds. Glassy microneedle structure was retained for all drugs stored at 2-8 °C under nitrogen for 3 months. Drug GFA classes informed glass stability under dry (nitrogen) environments at temperatures below their glass transition temperature. Under controlled humidity conditions, all glass microneedles crystallized, except for itraconazole. Drug GFA did not inform microneedle glass stability when exposed to water vapor during storage due to water absorption and glass plasticization. Itraconazole's glass stability was attributed to the interaction of absorbed water with liquid crystalline phases present in the itraconazole glass. The results highlight how glassy microneedle stability is informed by storage below Tg and glass interaction with moisture vapor. Results also demonstrate how the skin penetration efficiency of glassy microneedles is maintained during storage by selecting stabilizing storage conditions.

Microneedle-based nanodrugs for tumor immunotherapy.

Microneedle-based nanodrugs for tumor immunotherapy.

γ-polyglutamic acid-encapsulated metformin-loaded Ga-Car-MOF and hydrocaffeic acid-modified chitosan double-layer microneedle patch for accelerated bacterial-infected wound healing.

γ-polyglutamic acid-encapsulated metformin-loaded Ga-Car-MOF and hydrocaffeic acid-modified chitosan double-layer microneedle patch for accelerated bacterial-infected wound healing.

Transdermal Drug Delivery Systems: Integrating Modern Technology for Enhanced Therapeutics.

In recent years, transdermal drug delivery systems (TDDS) have gained popularity as a non-invasive, patient-friendly medication delivery method. This review article examines the latest transdermal medication delivery developments and breakthroughs. The review begins with a brief summary of transdermal medication administration, stressing the skin's barrier role and drug permeation methods. Novel materials and methods improve drug solubility, stability, and skin permeability in formulation technologies. A literature review of the most recent innovations in TDDS, such as nano-based delivery systems, microneedles, and smart patches, was conducted. Major challenges of drug solubility, stability, and skin permeability were carefully discussed, along with the transdermal patch designs of new therapeutic applications in pain management, cardiovascular diseases, and hormone therapy. Transdermal medication delivery difficulties may be overcome via nano-based drug delivery systems, microneedle arrays, and smart patches. Furthermore, the paper discusses current advances in transdermal patch design for therapeutic applications, highlighting effective instances in pain management, cardiovascular illness, and hormone therapy. The article examines transdermal medication delivery regulations, safety, and patient compliance in addition to technological advances. The complete study in this review seeks to help academics, doctors, and pharmaceutical professionals understand transdermal drug delivery and its future. Understanding recent advances in this field can help stakeholders design more effective and patient-friendly transdermal drug delivery systems, enhancing treatment outcomes and patient well-being.

Rapid Sampling of Large Quantities of Interstitial Fluid from Human Skin Using Microneedles and a Vacuum-assisted Skin Patch.

Interstitial fluid (ISF) is a promising diagnostic sample due to its extensive biomolecular content while being safer and less invasive to collect than blood. However, existing ISF sampling methods are time-consuming, require specialized equipment, and yield small amounts of fluid (<5 μL). We have recently reported a simple and minimally invasive technique for rapidly sampling larger quantities of dermal ISF using a microneedle (MN) array to generate micropores in the skin from which ISF is extracted using a vacuum-assisted skin patch. Here, we present step-by-step protocols for fabricating the MN array and skin patch, as well as for using them to sample ISF from human skin. Using this technique, an average of 20.8 μL of dermal ISF can be collected within 25 min, which is a ∼6-fold improvement over existing ISF sampling methods. Furthermore, the technique is well-tolerated and does not require the use of expensive or specialized equipment. The ability to collect ample volumes of ISF in a quick and minimally invasive manner will facilitate the analysis of ISF for biomarker discovery and its use for diagnostic testing. Key features • Minimally invasive (bloodless and nearly painless) technique for sampling ISF from human skin. • An average of 20.8 μL of interstitial fluid can be collected within 25 min. • This technique does not require expensive or specialized equipment or electricity. • Collected ISF can be analyzed using conventional laboratory-based assays or point-of-care diagnostic tests.

Leaf-Face Dendrobium Classifier Based on an Integrated Electrochemical Tongue and Machine Learning.

Botanical sourcing seriously impacts the safety and potency of herbal medicines, restricting the development of the traditional Chinese medicinal industry. Rapid and convenient identification of plant resources is important to address this problem. Herein, we innovated a portable, intelligent, and integrated platform, termed the Smart Electronic Tongue (SET), for right recognizing Dendrobium bonsai of different subspecies and origins. The device is miniaturized with a hollow microneedle array for leaf-face extraction, a press-pumping pipeline for on-demand sample sap suction, plus a five-electrode chip for electrochemical readout. Differential pulse voltammograms on three simplexes of self-assembled monolayers as well as their multiplexed configurations are specialized to generate high-dimensional fingerprinting of Dendrobium subtypes. Taking advantage of machine learning algorithms, the platform achieves automatic authentication over eight varieties with a discriminatory accuracy of 95%. Given this, we anticipate that such a bionic sensing setup would offer a versatile solution toward the classification of diverse officinals at the point of need.