Continuous glucose monitors are crucial for diabetes management, but invasive sampling, signal drift and frequent calibrations restrict their widespread usage. Microneedle sensors are emerging as a minimally-invasive platform for real-time monitoring of clinical parameters in interstitial fluid. Herein, a painless and flexible microneedle sensing patch is constructed by a mechanically-strong microneedle base and a thin layer of fluorescent hydrogel sensor for on-site, accurate, and continuous glucose monitoring. The Förster resonance energy transfer (FRET)-based hydrogel sensors are fabricated by facile photopolymerizations of acryloylated FRET pairs and glucose-specific phenylboronic acid. The optimized hydrogel sensor enables quantification of glucose with reversibility, high selectivity, and signal stability against photobleaching. Poly (ethylene glycol diacrylate)-co-polyacrylamide hydrogel is utilized as the microneedle base, facilitating effective skin piercing and biofluid extraction. The integrated microneedle sensor patch displays a sensitivity of 0.029 mM-1 in the (patho)physiological range, a low detection limit of 0.193 mM, and a response time of 7.7 min in human serum. Hypoglycemia, euglycemia and hyperglycemia are continuously monitored over 6 h simulated meal and rest activities in a porcine skin model. This microneedle sensor with high transdermal analytical performance offers a powerful tool for continuous diabetes monitoring at point-of-care settings.

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.

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 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.

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.

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.

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.

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.

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.

In diabetic patients with skin injuries, bacterial proliferation, accumulation of reactive oxygen species (ROS) in the tissues, and impaired angiogenesis make wound healing difficult. Therefore, eliminating bacteria, removing ROS, and promoting angiogenesis are necessary for treating acute diabetic wounds. In this study, benefiting from the ability of polyphenols to form a metal-phenolic network (MPN) with metal ions, TA-Eu MPN nanoparticles (TM NPs) were synthesized. The prepared photothermal agent CuS NPs and TM NPs were then loaded onto the supporting base and needle tips of PVA/HA (PH) microneedles, respectively, to obtain PH/CuS/TM microneedles. Antibacterial experiments showed that microneedles loaded with CuS NPs could remove bacteria by the photothermal effect. In vitro experiments showed that the microneedles could effectively scavenge ROS, inhibit macrophage polarization to the M1 type, and induce polarization to the M2 type as well as have the ability to promote vascular endothelial cell migration and angiogenesis. Furthermore, in vivo experiments showed that PH/CuS/TM microneedles accelerated wound healing by inhibiting pro-inflammatory cytokines and promoting angiogenesis in a diabetic rat wound model. Therefore, PH/CuS/TM microneedles have efficient antibacterial, ROS scavenging, anti-inflammatory, immunomodulatory, and angiogenic abilities and hold promise as wound dressings for treating acute diabetic wounds.