Macrophages play a pivotal role in the healing of diabetic ulcers. The sustained elevation of glucose levels damages the insulin signaling pathway in macrophages, leading to dysfunctional macrophages that struggle to transition from pro-inflammatory (M1) to reparative (M2) states. Therefore, modulating macrophage inflammatory responses via the insulin pathway holds promise for diabetic ulcer treatment. Additionally, the presence of biofilm impedes drug penetration, and the resulting immunosuppressive microenvironment exacerbates the persistent infiltration of pro-inflammatory M1 macrophages. Therefore, we designed an array of dissolvable microneedle (denoted as NPF@MN) loaded with self-assembled nanoparticles that could deliver NPF nanoparticles, acid-sensitive NPF-releasing Protocatechualdehyde (PA) with hypoglycemic and insulin-like effects, regulating macrophage polarization to an anti-inflammatory M2 phenotype. Additionally, this study extensively examined the mechanism by which NPF@MN accelerates the healing of diabetic ulcers through the activation of the insulin signaling pathway. Through RNA-seq and GSEA analysis, we identified a reduction in the expression of pathway-related factors such as IR, IRS-1, IRS-2, and SHC. Our work presents an innovative therapeutic approach targeting the insulin pathway in diabetic ulcers and underscores its translational potential for clinical management.

UNASSIGNED: Skin carcinoma, including malignant melanoma, basal, squamous, and Merkel cell carcinoma, present significant healthcare challenges. Conventional treatments like surgery and chemotherapy suffer from limitations like non-specificity, toxicity, and adverse effects. The upcoming treatments are dominated by nano-sized delivery systems, which improve treatment outcomes while minimizing side effects. Moving ahead, targeted nanoparticles allow localized delivery of drugs at tumor site, ensuring minimal damage to surrounding tissues.
UNASSIGNED: This review explores various targeting strategies for specific types of skin cancers. The strategies discussed include nanocarrier-mediated targeted delivery with multiple types of ligands like aptamers, antibodies, peptides, and vitamins and their advantages in skin cancer. Upcoming cutting-edge technologies such as smart delivery systems, microneedle-assisted delivery and three-dimensional printed scaffolds have also been discussed in detail. The findings in this review are summarized from databases like PubMed, Scopus, Web of Science, ClinicalTrials.gov, NIH, and articles published between 2005 and 2024 that discuss targeted therapy for skin cancer.
UNASSIGNED: Specific cancer-targeting strategies promise personalized treatments, improving response rates and reducing need for intensive therapies. The review highlights various challenges, their solution, and economic aspects in this dynamic field. It further emphasizes the potential for specialized strategies to revolutionize skin cancer treatment.

Carbon monoxide (CO) has emerged as a promising therapeutic agent, yet ensuring safe and precise CO delivery remains challenging. Here, we report a removable hydrogel-forming microneedle (MN) reactor for CO delivery via photocatalysis, with an emphasis on chemosensitization. Upon application, body fluids absorbed by the MNs dissolve the effervescent agents, leading to the generation of carbon dioxide (CO2) and triggering the release of the chemotherapeutics cisplatin. Meanwhile, the photocatalysts (PCs) trapped within MNs convert CO2 to CO under 660 nm light irradiation. These PCs can be removed by hydrogel-forming MNs, thereby mitigating potential biological risks associated with residual PCs. Both in vitro and in vivo experiments showed that MN-mediated CO delivery significantly improved tumor sensitivity to cisplatin by suppressing DNA repair, using an A375/CDDP melanoma model. This removable photocatalysis MN reactor offers safe and precise local delivery of CO, potentially creating new opportunities for CO or its combination therapies.

Wound healing is a dynamic process involving the timely transition of organized phases. However, infected wounds often experience prolonged inflammation due to microbial overload. Thus, addressing the viable treatment needs across different healing stages is a critical challenge in wound management. Herein, a novel core-shell microneedle (CSMN) patch is designed for the sequential delivery of tannic acid-magnesium (TA-Mg) complexes and extracellular vesicles from Lactobacillus druckerii (LDEVs). Upon application to infected sites, CSMN@TA-Mg/LDEV releases TA-Mg first to counteract pathogenic overload and reduce reactive oxygen species (ROS), aiding the transition to proliferative phase. Subsequently, the sustained release of LDEVs enhances the activities of keratinocytes and fibroblasts, promotes vascularization, and modulates the collagen deposition. Notably, dynamic track of microbial composition demonstrates that CSMN@TA-Mg/LDEV can both inhibit the aggressive pathogen and increase the microbial diversity at wound sites. Functional analysis further highlights the potential of CSMN@TA-Mg/LDEV in facilitating wound healing and skin barrier restoration. Moreover, it is confirmed that CSMN@TA-Mg/LDEV can accelerate wound closure and improve post-recovery skin quality in the murine infected wound. Conclusively, this innovative CSMN patch offers a rapid and high-quality alternative treatment for infected wounds and emphasizes the significance of microbial homeostasis.

UNASSIGNED: Scar is an unpleasant skin lesion that occurs following deep wounds or burns. The application of local triamcinolone is a common treatment for scar treatment and prevention, which should be repeated several times in conventional dosage forms. An effort has been made here to provide a prolonged triamcinolone dermal delivery by microneedle technology, which can also be used for wound closure.
UNASSIGNED: This study aimed to develop a long-lasting polylactic acid (PLA) microneedle patch for the prolonged release of triamcinolone acetonide (TrA) that could potentially be used for closure of wound edges and scar prevention and treatment.
UNASSIGNED: In this study, 3% and 10% TrA-containing polymeric microneedles were fabricated using the micro molding-solvent casting method. Optical microscopy, X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) were used for the characterization of microneedles. Mechanical strength was evaluated using a compression test and methylene blue staining. Additionally, the insertion depth was determined by histopathological sectioning of human skin samples and also insertion into Parafilm®M as a skin model. The in vitro drug release profile of the microneedles was studied over 34 days, and the kinetic model was determined. The ex-vivo skin permeation of TrA was studied using a Franz-diffusion cell.
UNASSIGNED: The TrA-containing PLA microneedles were fabricated with a uniform structure without any failure, deterioration, or loss of needles. Fourier-transform infrared spectroscopy and differential scanning calorimetry showed no interaction between TrA and PLA, and no effect on crystallinity and thermal behavior of TrA on polymer was detected. Microneedles showed appropriate mechanical properties, which were able to penetrate to about 900 - 1000 μm depth. Release profile from the whole body of 10% and 3% microneedle fitted to Higuchi model with cumulative amounts of 625 µg and 201.64 µg over 34 days. Release from the needles followed zero-order kinetic with cumulative amounts of 30.04 µg and 20.36 µg for 10% and 3%, respectively, for 34 days. Permeation was calculated to be 17 µg/day for 10% TrA-containing microneedle.
UNASSIGNED: The results suggested that suitable PLA microneedles containing TrA with prolonged release behavior can be successfully constructed with the solvent casting method.

Diabetes is a chronic disease with significant complications, necessitating regular treatment and checkups, which can be costly and time-consuming for patients. To address this, we developed the Sliding Microneedle (MN)-Lateral flow immunoassay strip (LFIAs) device that combines the advantages of MNs and LFIAs to detect IL-6, an independent biomarker for diabetes complications. This device offers rapid and highly sensitive detection of IL-6 by extracting interstitial fluid (ISF) through MNs and transferring it to LFIAs. The stainless MN, embedded in the 3D-printed Sliding MN-LFIAs device, was inserted into the skin at a 20° angle, minimizing blood contamination risk. With a filter paper attached to the MN surface, the device collected 4.65 ± 0.05 μL of ISF containing IL-6 within 90 s. The ISF was then transferred to the LFIAs using a running buffer. After a 15-min reaction, silver enhancement (SE) treatment was applied, allowing for the highly sensitive and specific detection of IL-6 at 102 pg/mL concentrations. The Sliding MN-LFIAs device successfully distinguished between normal and diabetic rat models, demonstrating its potential as an effective tool for detecting diabetes complications quickly and affordably.

A transdermal delivery system offers high bioavailability and favorable patient adherence, constituting an optimal approach for localized administration in rheumatoid arthritis (RA) treatment. However, the stratum corneum (SC) impedes the delivery efficiency of conventional transdermal drug delivery systems. Microneedles (MNs) can temporarily create micropores within the SC, enabling drug distribution via bypassing this barrier and enhancing transdermal delivery effectiveness. Notably, MNs provide a painless method of drug delivery through the skin and may directly modulate inflammation in immune cells by delivering drugs via the lymphatic system during transdermal administration. However, the MN delivery system is not suitable for drugs with low water solubility and stability. Additionally, major concerns exist regarding the safety of using MN delivery for highly cytotoxic drugs, given that it could result in high local drug concentration at the delivery site. While MNs exhibit some degree of targeted delivery to the immune and inflammatory environment, their targeting efficiency remains suboptimal. Nanoformulations have the potential to significantly address the limitations of MNs in RA treatment by improving drug targeting, solubility, stability, and biocompatibility. Therefore, this review provides a concise overview of the advantages, disadvantages, and mechanisms of different types of MNs for RA treatment. It specifically focuses on the application and advantages of combining nanoformulation with MNs for RA treatment and summarizes the current trends in the development of nanoformulations combined with MNs in the field of RA treatment, offering theoretical support for future advancements and clinical applications.

BACKGROUND: Anti-aging products are widely used, but the desire for safe and more efficient anti-aging products continues to increase. Dissolving microneedle patches (MNPs) have provided a more efficient transdermal drug delivery solution. MNP is a promising candidate for developing better anti-aging products.
OBJECTIVE: To develop a more efficient anti-aging MNP product, we fabricated a dual anti-wrinkle microneedle patch (named DA-MNP) using droplet extension (DEN®) technology and evaluated its skin puncture ability, safety, and efficacy through clinical studies.
METHODS: A DA-MNP comprising hyaluronic acid (HA) polymer backbone, acetyl octapeptide-3, and L-ascorbic acid 2-glucoside and sodium cyclic lysophosphatidic acid was fabricated using DEN® technology. Placebo MNPs comprising only HA were also fabricated. Twenty-four healthy subjects were enrolled in this comparative clinical study. The DA-MNP or placebo MNP was separately applied to the left and right eyes of subjects for overnight. Assessments, including wrinkle improvement, trans-epidermal water loss (TEWL), eye lifting and adverse effects were evaluated at each scheduled visit day for 28 days.
RESULTS: The DA-MNP showed mechanical strength enough for puncturing the stratum corneum. Compared to placebo MNP group, the DA-MNP treated group showed an effective eye wrinkles improvement and better anti-aging of skin, with reduced TEWL, enhanced skin elasticity and lifting, and no adverse effects.
CONCLUSIONS: The present study demonstrated that the fabricated DA-MNP exhibited fast acting on deep wrinkles and enhanced anti-aging efficacy, with no skin safety concern. Thus, this DA-MNP may serve as a new transdermal delivery solution for skin wrinkling and aging.

Photoaging holds remarkable importance for skin health and senescence. Ultraviolet (UV) irradiation results in the disruption of the extracellular matrix (ECM) microenvironment, the degradation of collagen, and the generation of oxidative stress. Traditional hyaluronic acid (HA) exhibits a diminished capacity to stimulate collagen regeneration, and hampered by its poor permeability as a macromolecule, ultimately resulting in constrained therapeutic outcomes for the treatment of photoaging. In this study, HA/PX was prepared by functional modification of HA with sulfonate-rich or phosphatidylcholine-rich polymers, which could complement the loss of ECM and ameliorate the senescence of human fibroblasts (HDFs) and hairless mouse models subjected to UVB-induced photoaging. The results indicate that HA/PX exhibits superior abilities in delaying cellular aging, promoting collagen regeneration, and resisting reactive oxygen species (ROS) compared to HA. Furthermore, HA/PX shows good biocompatibility both in vivo and in vitro, without causing allergic reactions or other adverse effects. We also demonstrated that the transdermal delivery of HA/PX via microneedle arrays (MNs) can significantly mitigate wrinkles and skin damage in photoaged nude mice, and achieve the treatment of skin photoaging by enhancing epidermal thickness, promoting collagen deposition, and reducing oxidative stress. Therefore, our research offers a novel possibility for future anti-aging therapeutic strategies.

Microneedles are an innovation in the field of medicine that have the potential to revolutionize drug delivery, diagnostics, and cosmetic treatments. This innovation provides a minimally invasive means to deliver drugs, vaccines, and other therapeutic substances into the skin. This research investigates the design and manufacture of customized microneedle arrays using laser ablation. Laser ablation was performed using an ytterbium laser on a polymethyl methacrylate (PMMA) substrate to create a mold for casting polydimethylsiloxane (PDMS) microneedles. An experimental design was conducted to evaluate the effect of process parameters including laser pulse power, pulse width, pulse repetition, interval between pulses, and laser profile on the desired geometry of the microneedles. The analysis of variance (ANOVA) model showed that lasing interval, laser power, and pulse width had the highest influence on the output metrics (diameter and height) of the microneedle. The microneedle dimensions showed an increase with higher pulse width and vice versa with an increase in pulse interval. A response surface model indicated that the laser pulse width and interval (independent variables) significantly affect the response diameter and height (dependent variable). A predictive model was generated to predict the microneedle topology and aspect ratio varying from 0.8 to 1.5 based on the variation in critical input process parameters. This research lays the foundation for the design and fabrication of customized microneedles based on variations in specific input parameters for therapeutic applications in dermal sensors, drug delivery, and vaccine delivery.