Assessment of microneedle array insertion into skin using Raman spectroscopic techniques.

Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution

Micropore closure kinetics are delayed following microneedle insertion in elderly subjects

Transcending epithelial and intracellular biological barriers; a prototype DNA delivery device

As the largest and most accessible organ in the body, with a surface area of 1.5–2 m 2 , the skin is an enticing target for drug delivery. Delivery of medication through the skin has expanded beyond the initial brief of topical delivery for local action to the transdermal application of drugs designed for systemic absorption and action. The principal obstacle to such transport is that of the stratum corneum, the outermost skin layer. To enable the delivery of a wider range of drug compounds and overcome the permeability barrier of the skin anatomy, microneedles (MNs) were born. MNs are a mechanical method of skin poration, first conceptualized in the 1970s [1]. Since manufacturing advances allowed the first practical realization in 1998 [2], MNs have demonstrated great promise as a novel drug delivery platform. MN arrays consist of a plurality of tiny projections on the micron scale arranged on a base plate. By bypassing the stratum corneum, its rate-controlling effect is nullified, allowing transdermal deliv ery of a much wider range of drug molecules than would be possible by passive diffusion, including macromolecules, such as biologics and vaccines. With a typical average length of 50–900 μm, MNs are long enough to penetrate to the dermis, but are short and narrow enough to avoid stimulation of dermal nerves or puncture of dermal blood vessels. Initially, MNs were typically prepared from silicon and metal. However, there is now great interest in the use of US FDA-approved polymeric materials for MN manufacture [3]. These materials are often inexpensive and widely available, amenable for MN manufacture without the use of harsh processing conditions, for example, elevated temperatures. Prepared from water-soluble polymers, dissolving MN arrays have the drug incorporated into the MN formulation and upon insertion, the MNs dissolve, releasing the drug in the viable skin layers. Such a strategy offers a number of advantages for the patient. As the MNs dissolve upon application, the dosage form is effectively self-disabling, meaning that not only is the reinsertion of the needles into another patient impossible, but there is also no risk of needle-stick injury to the healthcare professional, thereby reducing the overall risk of infection transmission. The question of disposal of MNs is also simplified, as with no sharp waste remaining, there is no need for safe disposal. Dissolving MN arrays have been used to deliver a range of compounds, from hydrophilic, low molecular weight drugs, to larger biopharmaceutical molecules, demonstrating the ability of such a platform to enhance transdermal delivery [4]. Indeed, the technology has progressed to human trials, with positive results recently published from a Phase 2a study for the delivery of human parathyroid hormone using a biodegradable MN technology called MicroCor ® , developed by Corium International, Inc. [5]. Another promising application for dissolving MNs is that of vaccination, capitalizing on the rich immune cell population in the skin,

Continuous sampling of interstitial fluids from the human skin is a key technique for clinical bioassays using micro total analysis (TAS) technologies. Here, we present a porous microneedle (MN) array to be connected to a custom-designed microfluidic system for the minimally invasive access to the dermis. The pores and surface of the porous PDMS array are covered with hyaluronic acid to enhance mechanical strength and to achieve a fluidic path of water inside the MN bodies. The fabricated MN array is capable to penetrate an agarose gel phantom and extracts water contained in the gel, indicating the fluidic connection between the MN array and the microfluidic system.

Separable double-layered microneedle-based transdermal codelivery of DOX and LPS for synergistic immunochemotherapy of a subcutaneous glioma tumor

Quantification methods comparing in vitro and in vivo percutaneous permeation by microneedles and passive diffusion

Microfabrication of dissolvable, swellable, and biodegradable polymeric microneedle arrays (MNs) were extensively investigated based in a nano sensitive fabrication style known as micromilling that is then combined with conventional micromolding technique. The aim of this study was to describe the polymer selection, and optimize formulation compounding parameters for various polymeric MNs. Inverse replication of micromilled master MNs reproduced with polydimethylsiloxane (PDMS), where solid out of plane polymeric MNs were subsequently assembled, and physicochemically characterized. Dissolvable, swellable, and biodegradable MNs were constructed to depth of less than 1 mm with an aspect ratio of 3.6, and 1/2 mm of both inter needle tip and base spacing. Micromolding step also enabled to replicate the MNs very precisely and accurate. Polymeric microneedles (MN) precision was ranging from ±0.18 to ±1.82% for microneedle height, ±0.45 to ±1.42% for base diameter, and ±0.22 to ±0.95% for interbase spacing. Although dissolvable sodium alginate MN showed less physical robustness than biodegradable polylactic-co-glycolic acid MN, their thermogravimetric analysis is of promise for constructing these polymeric types of matrix devices.

Arrays of microneedles (MNAs) are integrated in an out-of-plane fashion with a base plate and can serve as patches for the release of drugs and vaccines. We used soft-lithography and micromolding to manufacture ceramic nanoporous (np)MNAs. Failure modes of ceramic npMNAs are as yet poorly understood and the question remained: is our npMNA platform technology ready for microneedle (MN) assembly into patches? We investigated npMNAs by microindentation, yielding average crack fracture forces above the required insertion force for a single MN to penetrate human skin. We further developed a thumb pressure-actuated applicator-assisted npMNA insertion method, which enables anchoring of MNs in the skin by an adhesive in one handling step. Using a set of simple artificial skin models, we found a puncture efficiency of this insertion method a factor three times higher than by applying thumb pressure on the npMNA base plate directly. In addition, this new method facilitated zero MN-breakage due to a well-defined force distribution exerted onto the MNs and the closely surrounding area prior to bringing the adhesive into contact with the skin. Owing to the fact that such parameter space exists, we can conclude that npMNAs by soft lithography are a platform technology for MN assembly into a patch.

Microneedles (MNs) have drawn rising attention owing to their merits of convenience, noninvasiveness, flexible applicability, painless microchannels with boosted metabolism, and precisely tailored multifunction control. MNs can be modified to serve as novel transdermal drug delivery, which conventionally confront with the penetration barrier caused by skin stratum corneum. The micrometer-sized needles create channels through stratum corneum, enabling efficient drug delivery to the dermis for gratifying efficacy. Then, incorporating photosensitizer or photothermal agents into MNs can conduct photodynamic or photothermal therapy, respectively. Besides, health monitoring and medical detection by MN sensors can extract information from skin interstitial fluid and other biochemical/electronic signals. Here, this review discloses a novel monitoring, diagnostic, and therapeutic pattern by MNs, with elaborate discussion about the classified formation of MNs together with various applications and inherent mechanism. Hereby, multifunction development and outlook from biomedical/nanotechnology/photoelectric/devices/informatics to multidisciplinary applications are provided. Programmable intelligent MNs enable logic encoding of diverse monitoring and treatment pathways to extract signals, optimize the therapy efficacy, real-time monitoring, remote control, and drug screening, and take instant treatment.

Hollow microneedle (MN) arrays offer versatility and control to transdermal drug delivery systems where a variety of drugs and their continuous supply are concerned. They may be used as a standalone device or be integrated with the drug reservoir or micropump. An important aspect in this regard is the effective fluidic communication between the reservoir and the MNs on a robust substrate. In a novel attempt of its kind, we present the development hollow SU-8 MNs on a pre-etched silicon wafer having through holes. SU-8 MNs are fabricated by direct laser writing by aligning them on the silicon substrate with microfluidic ports pre-etched by wet chemical etching. Each process step was optimized after a parametric study. The optimized MNs (500–600 µm length, 100 µm outer diameter and 40 µm inner diameter) have an aspect ratio of 5. The MNs have been characterized for mechanical strength and biological insertion tests for their effectiveness in puncturing the skin without breaking. The maximum compressive force and bending forces for the MNs are 0.27 N and 0.022 N per needle, which are higher than the resistive skin penetrating forces. The microfluidic characterizations show the development of hollow MN lumen with a flowrate of around 0.93 µl s−1 at 2 KPa pressure difference at the inlet. The array of 10 × 10 MNs with 500 µm spacing was able to successfully penetrate mice and rat skin without any breakage.

This study describes the processing of microneedle (MN) arrays with three different heights of arrowhead (600 µm (A1), 800 µm (A2), and 1000 µm (A3)), pyramid (600 µm (P1), 800 µm (P2), and 1000 µm (P3)), and turret (600 µm (T1), 800 µm (T2), and 1000 µm (T3)) designs using a digital light processing (DLP)-based 3D printing method. The 3D-printed MNs were examined for their morphological characteristics and mechanical performance. Scanning electron microscopy (SEM) imaging confirmed that all of the MNs were fabricated without fracture or bending. Each design exhibited distinct structural characteristics: arrowhead MNs displayed a well-defined morphology with sharp tips, pyramid MNs showed slight layering, and turret MNs, characterized by a wider base and sharp tips, had a smoother surface compared to the other designs. Mechanical tests revealed that the arrowhead MNs carried less load and were more prone to bending, while the pyramid and turret designs provided higher mechanical stability and penetration capacity. The pyramid design (P3) showed the highest mechanical strength, while turret MNs offered a more stable performance despite lower penetration capacity. These findings highlight the critical role of geometric design in optimizing MN performance for effective transdermal drug delivery.

Three-dimensional (3D) printing has transformed the development of microneedle arrays (MNAs) by enabling exceptional control over their geometry, distribution, materials, and functionality in a single-step, customizable process. This review represents a design-centric framework that organizes recent advancements in four interconnected levers: (i) individual microneedle (MN) geometry and size; (ii) patch-level MN distribution and multi-array architectures; (iii) computer-aided design (CAD), finite element analysis (FEA), computational fluid dynamics (CFD), and artificial intelligence/machine learning (AI/ML)-driven optimization; and (iv) manufacturing constraints and emerging solutions for scalability and reproducibility. Outcomes show that small changes in the radius of the MN’s tip, the MN’s aspect ratio, the MN’s internal lattice architecture, and the spacing of the array can dramatically influence their insertion force, mechanical reliability, payload capacity, and therapeutic coverage. Now, digital tools can bridge the design and experimental outcomes, while novel morphologies, hybrid materials, and theranostic integrations are expanding the clinical potential of MNs. The remaining challenges, resolution-versus-throughput trade-offs, biocompatibility, batch-to-batch consistency, and lack of testing standardization are examined alongside promising directions in high-throughput 3D printing, stimuli-responsive materials, and closed-loop systems. Finally, rational, model-guided design strategies are positioning 3D-printed MNAs as versatile platforms for painless, patient-specific drug delivery, diagnostics, and personalized medicine.

We describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33mg (90%) of the drug initially loaded into the arrays was delivered over 24h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263μgml−1 at the 24h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10cm2 could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs.

Mechanical strength affecting the penetration in microneedles and PLGA nanoparticle-assisted drug delivery: Importance of preparation and formulation