Microneedle Patch Research Articles

Dual-functional core–shell microneedle patches for oral ulcers treatment

Microneedle patches have been widely used in transdermal drug delivery due to their painless and enhanced drug delivery. Despite their established success, their application within the oral cavity, characterized by a dense distribution of nociceptor, remains largely unexplored. Here, we introduce a well-designed dual-functional core–shell microneedle patches to address oral ulcers. The outer shell of the microneedle tips is crafted from hyaluronic acid (HA) and loaded with lidocaine, while the inner core, composed of gelatin methyl methacrylate (GelMA) encapsulates dexamethasone. The HA shell rapidly dissolves upon application, facilitating the immediate release of lidocaine to induce anesthesia at the ulcer site, thereby alleviating the associated painful sensations. Simultaneously, GelMA imparts mechanical strength and ensured the sustained release of dexamethasone. In vivo experiments further demonstrated that the Dex@MN group exhibiting the most rapid healing rate also displayed the highest levels of collagen deposition and the lowest concentrations of inflammatory factors. This collective evidence underscores the considerable potential of dual-functional core–shell microneedle patches in the treatment of oral diseases.

Production of microneedle patches coated with polyvinyl-alcohol/sucrose/gentamicin sulfate for skin treatment

In this study, resin-based microneedle (MN) patches were fabricated using a digital light processing (DLP) printer. The needles were coated with gentamicin sulfate (GEN)-loaded with 13.3 % PVA/25 % sucrose solution by immersion. The SEM results showed that the coating was homogeneous and uniformly conical. Analysing the in vitro release profiles of GEN, it was found that it was ultimately released within 312 h. The compression test results demonstrated that GEN addition increased the compression strength to the value of 2.17 ± 0.01 N/mm2.

Electrically-driven drug delivery into deep cutaneous tissue by conductive microneedles for fungal infection eradication and protective immunity

Fungal infections affect over 13 million people worldwide and are responsible for 1.5 million deaths annually. Some deep cutaneous fungal infections may extend the dermal barriers to cause systemic infection, resulting in substantial morbidity and mortality. However, the management of deep cutaneous fungal infection is challenging and yet overlooked by traditional treatments, which only offer limited drug availability within deep tissue. In this study, we have developed an electrically stimulated microneedle patch to deliver miconazole into the subcutaneous layer. We tested its antifungal efficacy using in vitro and ex vivo models that mimic fungal infection. Moreover, we confirmed its anti-fungal and wound-healing effects in a murine subcutaneous fungal infection model. Furthermore, our findings also showed that the combination of miconazole and applied current synergistically stimulated the nociceptive sensory nerves, thereby activating protective cutaneous immunity mediated by dermal dendritic and γδ-T cells. Collectively, this study provides a new strategy for minimally invasive delivery of therapeutic agents and the modulation of the neuro-immune axis in deep tissue.

Magnesium metal-organic framework microneedles loaded with curcumin for accelerating oral ulcer healing.

Oral ulcers are a common oral mucosal disease that seriously affect the quality of life. Traditional drug treatments have shown unsatisfactory efficacy and potential adverse reactions. In this study, curcumin-loaded multifunctional magnesium metal-organic framework-embedded hyaluronic acid-soluble microneedles patches were developed to optimize treatment strategies for oral ulcers. This microneedles patch achieves efficient release of curcumin and Mg2+ in the ulcer through precisely targeted delivery and controllable release mechanism, significantly regulates inflammation, promotes cell migration and angiogenesis, and accelerates the ulcer healing process. At the same time, the synergistic effect of curcumin and gallic acid effectively alleviated oxidative stress, while the backplate ε-poly-L-lysine and needle tip Mg2+ jointly constructed an antibacterial barrier to effectively inhibit pathogens. Verification using an oral ulcer rat model showed that the microneedles patch exhibited excellent therapeutic effects. This not only opens up a new avenue for clinical oral treatment but also marks a breakthrough in nanobiomaterials science and drug delivery technology and heralds a broad prospect in the field of oral ulcer treatment in the future.

Responsive porous microneedles with riboflavin ocular microinjection capability for facilitating corneal crosslinking

Riboflavin-5-phosphate (riboflavin) is the most commonly used photosensitizer in corneal crosslinking (CXL); while its efficient delivery into the stroma through the corneal epithelial barrier is challenging. In this paper, we presented novel responsive porous microneedles with ocular microinjection capability to deliver riboflavin controllably inside the cornea to facilitate CXL. The microneedle patch was composed of Poly (N-isopropyl acrylamide) (PNIPAM), graphene oxide (GO), and riboflavin-loaded gelatin. After penetrating the cornea by the stiff and porous gelatin needle tip, the photothermal-responsive characteristic of the PNIPAM/GO hydrogel middle layer could realize the contraction of the gel under the stimulation of near-infrared light, which subsequently could control the release of riboflavin from the backing layer into the cornea stromal site both in vitro and in vivo. Based on the microneedles system, we have demonstrated that this microinjection technique exhibited superior riboflavin delivery capacity and treatment efficacy to the conventional epithelial-on protocol in a rabbit keratoconus model, with benefits including minimal invasiveness and precise administering. Thus, we believe the responsive porous microneedles with riboflavin ocular microinjection capability are promising for clinical corneal crosslinking without epithelial debridement.

The efficacy of light-guiding microneedle patch for stimulating hair growth in androgenetic alopecia.

Androgenetic alopecia (AGA) is the most common form of hair loss characterized by miniaturization of hair follicles. Low-level light therapy (LLLT) and microneedling have shown potential in promoting hair regrowth. This study aims to evaluate the efficacy of an innovative light-emitting diode (LED) helmet cooperated with a novel light-guiding microneedle patch (LMNP) for stimulating hair growth in AGA. In this randomized clinical trial, 16 AGA patients received treatments using light-guiding microneedle patches (LMNPs) illuminated by a LED helmet equipped with green (522nm) and red (633nm) LEDs, delivering 50mW/cm2 power and 40J/cm2 energy. Treatments were applied weekly for 24weeks, targeting the frontal recession area. The right side of the scalp was treated with green light and the left with red light, each combined with a LMNP featuring 900µm height needles at a density of 105 per square centimeter. Hair density and diameter, along with patient and physician satisfaction scores, were assessed monthly. Both red and green LED treatments with LMNP, significantly enhanced hair density and diameter. Satisfaction scores, as reported by both physicians and participants, increased over time. Comparative analyses revealed no statistically significant differences in average satisfaction scores or in changes in hair density and diameter between the groups by the end of the study. Additionally, no serious adverse effects were reported, highlighting the safety of the treatments. The combined Light sources which is portable LED helmet and LMNPs shows promise as a non-invasive, effective treatment for AGA, with similar efficacy between red and green wavelengths.

Microneedle Transdermal Patches- A Novel Painless Approach with Improved Bioavailability for the Treatment of Diseases with Special Prevalence to Neonatal Infection.

Microneedle transdermal drug delivery systems (TDDS) present a compelling substitute for parenteral and oral administration methods in the treatment of several illnesses. The past several decades have seen a revolution in technology that has changed the production of micro-structured devices, including the development of microneedles for transdermal patches. These devices are used to deliver drugs, proteins, insulin, antibiotics, vaccinations, and other therapies through the skin. They are proven to be beneficial for the prevention of newborn infections. Successful treatments for conditions like cancer, diabetes, rheumatoid arthritis, Alzheimer’s disease, and migraines can be achieved with the use of transdermal microneedle patches. Microneedles have the potential to offer prolonged immunity, dosage sparing, and improved protection against viral challenges. The epidermis and dermis are immunologically rich layers, and because of the needles’ micron-size structure, these devices have shown to be significantly more effective at targeting these layers, indicating their potential utility in the creation of next-generation vaccines. Within the framework of developing vaccines. Microneedle transdermal patches’ main benefits are that they are easy to use, painless, and non-invasive. Here, we discuss the types of microneedle transdermal patches and how microneedle transdermal patches are now being used to treat infections in newborns and vaccination and as a more cost-effective self-administration approach. This also enhances the bioavailability when used in vaccination therapy. Next, we’ll go over how microneedle transdermal patches are currently used to treat a variety of illnesses effectively, including those that affect newborns.

Lidocaine-Loaded Iontophoresis-Driven Fiber-Based Microneedle Patch for Controllable and Long-Lasting Transdermal Local Analgesia

AbstractThe acute pain induced by clinical procedures, such as venipuncture, dental operations, and dermatological treatments, as well as postoperative pain, drives the advancement of anesthetic techniques aimed at alleviating discomfort. This situation underscores the ongoing significance of effective pain management strategies within the field of anesthesia. This paper presents an integrated iontophoresis (ITP)-driven fiber-based microneedle patch (IFMP) regulated by a smartphone for controllable, long-lasting lidocaine transdermal delivery. The IFMP integrates pure cotton fiber canvas-based dissolving microneedles (MNs) with ITP into a patch, with the MNs tips and gel layers significantly increasing the drug-loading capacity, achieving a one-step drug administration strategy of “dissolution, diffusion, and ITP.” Lidocaine is released via the microchannels of MNs by passive diffusion. Additionally, an electric current initiates active ITP for lidocaine delivery, creating synergy. User-requirement-based drug release by precisely modulating electrical signals in rat pain models is described herein. A smartphone application enables precise dosage control. It offers three different delivery modes: single-dose, pulse delivery, and sustained-release, ensuring rapid onset, and long-lasting pain relief. This versatility makes the system suitable for various pain conditions. The IFMP represents a promising system for patient-controlled local analgesia treatment, enabling active and long-term local self-controlled pain management in a safe and regulated manner. Graphical Abstract The iontophoresis-driven fiber-based microneedle patch combines fiber-based dissolving microneedles with iontophoresis, facilitating controlled lidocaine release through diffusion and electrical activation for enhanced effect. Precise modulation of electrical signals allows user-requirement-based drug release in rat pain models. A smart application supports precise dosing in single-dose, pulse, or sustained-release modes, ensuring efficient and prolonged pain management.

Oregano essential oil-infused mucin microneedle patch for the treatment of hypertrophic scar

Hypertrophic scar (HS) manifests as abnormal dermal myofibroblast proliferation and excessive collagen deposition, leading to raised scars and significant physical, psychological, and financial burdens for patients. HS is difficult to cure in the clinic and current therapies lead to recurrence, pain, and side effects. In this study, a natural amphiphilic polymer mucin is used to prepare a dissolving microneedle (muMN) that is loaded with oregano essential oil (OEO) for HS therapy. muMN exhibits sufficient skin/scar tissue penetration, quick skin recovery time after removal, good loading of natural essential oil, fast dissolution and detachment from the base layer, and good biocompatibility to applied skin. In the rabbit HS model, OEO@muMN shows a significant reduction in scar thickness, epidermal thickness index, and scar elevation index. OEO@muMN also attenuates the mean collagen area fraction and decreases the number of capillaries in scar tissues. Biochemical Assay reveals that OEO@muMN significantly inhibits the expression of transforming growth factor-β1 (TGF-β1) and hydroxyproline (HYP). In summary, this study demonstrates the feasibility and good efficacy of using the anti-proliferative and anti-oxidative OEO for HS treatment. OEO@muMN is an efficient formulation that holds the potential for clinical anti-HS application. muMN is an efficient platform to load and apply essential oils transdermally.

An antimicrobial microneedle patch promotes functional healing of infected wounds through controlled release of adipose tissue-derived apoptotic vesicles

The high incidence and mortality rates associated with acute and chronic wound infections impose a significant burden on global healthcare systems. In terms of the management of wound infection, the reconstruction and regeneration of skin appendages are essential for the recovery of mechanical strength and physiological function in the regenerated skin tissue. Novel therapeutic approaches are a requisite for enhancing the healing of infected wounds and promoting the regeneration of skin appendages. Herein, a novel antimicrobial microneedle patch has been fabricated for the transdermal controlled delivery of adipose tissue-derived apoptotic vesicles (ApoEVs-AT@MNP) for the treatment of infected wounds, which is expected to achieve high-quality scarless healing of the wound skin while inhibiting the bacteria in the infected wound. The microneedle patch (MNP) system possesses adequate mechanical strength to penetrate the skin, allowing the tips to remain inside tissue for continuous active release of biomolecules, and subsequently degrades safely within the host body. In vivo transplantation demonstrates that ApoEVs-AT@MNP not only inhibits bacterial proliferation in infected wounds but also significantly promotes effective and rapid scarless wound healing. Particularly noteworthy is the ability of ApoEVs-AT@MNP to promote the rapid formation of mature, evenly arranged hair follicles in infected wounds, observed as early as 8 days following implantation, which is essential for the restoration of skin function. This rapid development of skin appendages has not been reported this early in previous studies. Therefore, ApoEVs-AT@MNP has emerged as an excellent, painless, non-invasive, and highly promising treatment for infected wounds.

Dual-continuous microneedle patch integrating transdermal delivery of pH-sensitive licorzinc MOFs and Zn2+ hydrogel sensors for treating alopecia areata

Licorzinc is a commonly used immunomodulator, but faces poor water solubility, high oral dose, and side effects of zinc accumulation by long-term administration. Herein, a new licorzincform was developed by adsorbing glycyrrhizic acid (GA) into zeolitic imidazolate framework-8 (GA@ZIF-8) with superior solubility and acid-responsive drug release properties. Then, a dual-continuous microneedle patch was developed for simultaneous transdermal delivery of GA@ZIF-8 and monitoring Zn2+ in local tissues, where dissolving microneedles as a drug delivery unit were fabricated from hyaluronic acid. In contrast, swollen hydrogel microneedles as a diagnostic unit were prepared from double cross-linking of N-acryloyl-glycinamide and α-methylacrylic acid and hybridized with Eu3+ and terpyridine (TPy). The microneedles for transdermal GA@ZIF-8 delivery were completely dissolved in 2 min, which improved the cyclophosphamide-induced hair follicle recession in mice by reducing CD8+NKG2D+ T cells infiltration, inhibiting Jak receptor activation, and decreasing IL-15 and IFN-γ. Additionally, as a sensor unit, the microneedles rapidly absorbed water swelled when stabbed into the skin, and fluoresced red when exposed to 365 nm light. Zn2+ in the inter tissue fluid competes with Eu3+ in the TPy-Eu3+ complex and coordinates with Tpy, which triggers a change in fluorescence. Notably, the detection Zn2+concentration range was 10–8 M–10–1 M, and it was not disturbed by metal ions including Na+, K+, Mg2+, and Ca2+, suggesting that it is competent to be applied as a real-time chemosensor of Zn2+. Collectively, this newly designed system with both therapeutic and diagnostic functions provides a new strategy for treating zinc-related diseases.

Hydrogel Capacitors Based on MoS2 Nanosheets and Applications in Glucose Monitoring.

Non-invasive/minimally invasive continuous monitoring of blood glucose and blood glucose administration have a high impact on chronic disease management in diabetic patients, but the existing technology is yet to achieve the above two purposes at the same time. Therefore, this study proposes a microfluidic microneedle patch based on 3D printing technology and an integrated control system design for blood glucose measurement, and a drug delivery control circuit based on a 555 chip. The proposed method provides an improved preparation of a PVA-PEG-MoS2 nanosheet hydrogel, making use of its dielectric properties to fabricate a microcapacitor and then embedding it in a microfluidic chip. When MoS2 nanosheets react with interstitial liquid glucose (and during the calibration process), the permittivity of the hydrogel is changed, resulting in changes in the capacitance of the capacitor. By converting the capacitance change into the square-wave period change in the output of the 555 chip with the control circuit design accordingly, the minimally invasive continuous measurement of blood glucose and the controlled release of hypoglycemic drugs are realized. In this study, the cross-linking structure of MoS2 nanosheets in hydrogel was examined using infrared spectroscopy and scanning electron microscopy (SEM) methods. Moreover, the critical doping mass fraction of MoS2 nanosheets was determined to be 2% via the measurement of the dielectric constant. Meanwhile, the circuit design and the relationship between the pulse cycle and glucose concentration is validated. The results show that, compared with capacitors in series, the microcapacitors embedded in microfluidic channels can be connected in parallel to obtain better linearized blood glucose measurement results.

Energy-based methods and nanocarrier-based approaches for melasma treatment

Melasma is a chronic disease caused by excessive melanin production in the skin, affecting the quality of life, especially in women. As a kind of skin hyperpigmentation, it can be caused by sun exposure, genetics, hormones, drugs, or inflammation. Melasma treatment can be effective when the product penetrates well into the skin. As an essential skin barrier, the stratum corneum displays a significant role in topical and transdermal drug delivery. In this regard, numerous strategies have been developed to increase the skin permeability and efficiency of drugs. This review explores energy-based methods and nanocarrier-based approaches for melasma treatment, focusing on enhancing drug delivery to the viable epidermis and overcoming SC. Physical methods have some advantages like increasing the skin penetration and also some drawbacks, including frequent visits, high costs, and the need for advanced equipment and trained operators. Further, these methods are often combined with high energy and special technics. As an emerging physical-based method that could be used to treat patients with multiple medications, microneedle patch is drawing interest due to its ease of use, ability to pinpoint drug delivery, and fewer side effects. In addition, they can penetrate drug molecules into deeper layers of skin and provide more sustainable results compared to conventional methods. Nanocarrier-based systems like transferosome and ethosome (deformable liposomes) are also effective options for skin penetration and treating melasma and skin hyperpigmentation. Despite several benefits, such as high entrapment efficiency, good permeation, and increased bioavailability of drugs through the skin, their stability problems and limitations toward nanoparticle production on an industrial scale are the most significant drawbacks of this method. In the current review, we looked at the articles published between 2010 and August 2023 on energy-based methods and nanocarriers-based approaches have been used to treat melasma.

PSIII-28 Evaluation of tissue and plasma meloxicam concentrations using a microneedle patch for drug delivery

Abstract The objective of this study was to evaluate plasma and ear tissue meloxicam concentrations when the drug was delivered using two different formulations of a microneedle patch placed on the back of the ear. Nursing pigs [n = 10; body weight (BW) = 3.64 ± 0.32 kg) from 1 litter were assigned randomly to 1 of 2 treatment groups. Patches delivered 2.5 mg of meloxicam/kg BW to pigs regardless of formulation, with the differences in patches being based on type of polymer located on the microneedles and base of the patch. Treatment groups were: 1) pigs receiving a microneedle patch with collagen, polyvinyl alcohol (PVA), and meloxicam on the microneedles, with PVA and chitosan on the base (n = 6 pigs; Patch A); and 2) pigs receiving a microneedle patch with chitosan, PVA, and meloxicam on the microneedles, with collagen and PVA on the base (n = 4 pigs; Patch B). During the study, pigs remained in the crate with the sow and littermates. An Estrotect Breeding Indicator strip was used to adhere the microneedle patch on the ear of the pigs. Blood was collected at study initiation prior to patch administration (0 h) and 24 and 48 h for plasma meloxicam analysis. To evaluate tissue meloxicam concentrations, 3 pigs that received Patch A and 2 pigs that received Patch B were humanely euthanized after blood collection and patch removal at 24 and 48 h, with the entirety of the ear removed for analysis. Statistical analyses were performed using the MIXED procedure of SAS 9.4 (Cary, NC) to assess the effects of treatment, hour, and treatment × hour interaction. Statistical significance was determined at P ≤ 0.05, with tendencies at 0.05 < P ≤ 0.1. There were no differences (P = 0.83) between patch formulations for tissue meloxicam concentrations (Patch A = 6.55 ± 2.12 ng/mg; Patch B = 7.32 ± 2.60 ng/mg). Plasma concentrations were not detectable at any time point, but tissue concentrations of meloxicam were detectable for pigs that received either patch formulation at 24 (5.44 ± 2.37 ng/mg) and 48 h (8.42 ± 2.37 ng/mg). There were no differences (P = 0.41) between patch formulations for tissue meloxicam concentrations at either timepoint, nor was there an interaction of patch formulation and hour (P = 0.73). It is unknown why the meloxicam did not diffuse from the ear tissue into the plasma; however, further studies will focus on applying the microneedle patch at different areas on the animal to allow for optimal diffusion through the skin and into blood circulation for pain mitigation in livestock animals.

Dissolving microneedle patches for delivery of amniotic mesenchymal stem cell metabolite products for skin regeneration in UV-aging induced mice

Microneedles offer a promising solution to enhancing dermal delivery of amniotic mesenchymal stem cell metabolite product (AMSC-MP), which contains hydrophilic protein components with high molecular weight, for the purposes of skin rejuvenation and improving human health. This study aimed to evaluate the physicochemical characteristics and in vivo efficacy of AMSC-MP-loaded microneedle patches for effectively regenerating skin tissues in UV-aging induced mice. Dissolving microneedle patches, composed of polyvinyl alcohol with an MW of 9–10 kDa and polyvinylpyrrolidone with an MW of 56 kDa, were fabricated using the double-casting method at three AMSC-MP concentrations: i.e., 30 % (MN30), 25 % (MN25), and 20 % (MN20). The microneedles patches were then evaluated for morphological, mechanical resistance, and insertion properties. An ex vivo release study was also conducted using the Franz cell method, and in vivo efficacy and irritation were then determined through collagen density scores, fibroblast cell counts, and skin irritation studies of UV-aging induced mice. The AMSC-MP microneedles displayed a pyramidal shape with 500 µm sharp tips. Mechanical testing revealed that MN30 achieved its deepest insertion into Parafilm® M (447.44 ± 37.21 µm), while MN25 achieved its deepest insertion into full-thickness porcine skin (717.92 ± 25.40 µm). The study revealed a controlled EGF release for up to 24 h, with MN20 exhibiting the highest deposition (55.94 ± 12.34 %). These findings demonstrate the successful penetration of microneedles through the stratum corneum and viable epidermis. Collagen density scores and fibroblast cell counts were significantly higher in all microneedle formulations than the control, with MN30 having the highest values. Inflammatory cell counts indicated minimal presence suggesting non-irritation in the in vivo study. Dissolving microneedle patches exhibited favorable characteristics and efficiently delivered AMSC-MP with minimal potential for irritation, providing potential technology for delivering biological anti-aging agents for the purposes of fostering skin regeneration.

Long-term storage and intradermal vaccination of tumor-derived exosomes via sugar microneedles for improving tumor immunotherapies

Tumor-derived exosomes are gaining recognition as a promising cancer vaccine for immunotherapies due to their abundant tumor antigens and their role as endogenous carriers for antigen delivery. However, challenges including unstable membrane structures and compromised protein integrity during long-term storage, as well as the absence of effective delivery methods, restrict their clinical applications. Herein, we introduce an exosomes-loaded sugar microneedle (EXO-SMN) patch that not only allows for the long-term storage of exosomes but also facilitates intradermal delivery to enhance immunotherapies. By employing a two-casting micro-molding method, the EXO-SMN patch is composed of an array of tips simply made from trehalose, with a polyvinylpyrrolidone backing. The EXO-SMN patch demonstrates the capability to effectively protect the loaded exosomes, maintaining their membrane structure and protein integrity even after being stored at room temperature for at least one month. Additionally, the EXO-SMN patch possesses strong mechanical properties for skin penetration, facilitating the rapid release of exosomes into the skin within 120 s, and prolonging exosome retention in both skin and lymph nodes compared to intravenous (IV) or subcutaneous (SC) injections. Intradermal vaccination of tumor-derived exosomes via the EXO-SMN patch elicited higher antigen-specific immune responses and resulted in slower tumor growth compared to IV or SC injection. Given its easy to use and reliability, the proposed EXO-SMN patch could eventually facilitate the storage and delivery of exosomes in various biomedical applications.

Intelligent luminescent microneedle and hydrogel patches for visual monitoring of lactic acid and dopamine

Dopamine (DA) and lactic acid (LA) are vital biochemical indicators of neurotransmitters and tissue oxidation monitoring, which can comprehensively assess the neurological and physical conditions. The combination of fluorescent sensor and artificial intelligence shows great potentials in monitoring and quantizing of human biochemicals. Herein, a Tb3+ functionalized hydrogen-bonded organic framework material (Tb@ME-TPA) is synthesized based on coordination post-synthesis modification, and its sensing mechanism for DA and LA is investigated by experiments and theoretical calculations. For visual detection of DA and LA in actual environment, Tb@ME-TPA is fabricated into PVA films and microneedle patches, which hold the advantages of high efficiency, sensitivity and anti-interference. In addition, microneedles-based probe for minimally invasive sensing of DA in the dermal interstitial fluid along with a portable smartphone platform are designed to monitor with high accuracy. Furthermore, an intelligent back-propagation neural network model based on fluorescence image recognition is constructed, which can combine optical sensing of LA with deep learning by computer, greatly improving the efficiency and accuracy. This work not only presents a novel idea for the integration of fluorescent materials, smartphones and deep learning, but also provides an effective method for the prediction of diseases as well as the real-time monitoring of overall well-being.

Glucose-Responsive Microneedle Patch with High Insulin Loading Capacity for Prolonged Glycemic Control in Mice and Minipigs.

Transdermal microneedle-mediated glucose-responsive insulin delivery systems can modulate insulin release based on fluctuations in blood glucose levels, thus maintaining normoglycemia effectively in a continuous, convenient, and minimally invasive manner. However, conventional microneedles are limited by the low drug loading capacity, making it challenging to be applied on human skin at a reasonable size for a lasting glucose-controlling effect, thus hindering their clinical translation. Here, we design a microneedle patch with a solid insulin powder core to achieve a high loading capacity of insulin (>70 wt %) as well as a glucose-sensitive polymeric shell to realize glucose-responsive insulin release. Once exposed to hyperglycemia, the formation of negatively charged glucose-boronate complexes increases the charge density of the shell matrix, leading to swelling of the shell and accelerating insulin release from the core. We have demonstrated that this glucose-responsive microneedle patch could achieve long-term regulation of blood glucose levels in both type 1 diabetic mice and minipigs (up to 48 h with patches of ∼3.5 cm2 for minipigs >25 kg).

Photothermal Fish Gelatin-Graphene Microneedle Patches for Chronic Wound Treatment.

Microneedles are demonstrated as an effective strategy for chronic wound treatment. Great endeavors are devoted to developing microneedles with natural compositions and potent functions to promote therapeutic effects for wound healing. Herein, a novel graphene oxide-integrated methacrylated fish gelatin (GO-FGelMA) microneedle patch encapsulated with bacitracin and vascular endothelial growth factor (VEGF) is developed for chronic wound management. As the natural components and porous structures of FGelMA, the fabricated microneedle patches display satisfactory biocompatibility and drug-loading ability. Owing to the integration of graphene oxide, the microneedle patches can realize promoted drug release via near-infrared (NIR) irradiation. Besides, the encapsulated bacitracin and VEGF endow the microneedle patches with the ability to inhibit bacterial growth and promote angiogenesis. It is demonstrated that the GO-FGelMA microneedle patches with efficient drug release exert a positive influence on the wound healing process through reduced inflammation, enhanced wound closure, and improved tissue regeneration. Thus, it is believed that the proposed drugs-loaded GO-FGelMA microneedle patches will hold great potential in future chronic wound treatment.

Emerging Trends in Dissolving-Microneedle Technology for Antimicrobial Skin-Infection Therapies.

Skin and soft-tissue infections require significant consideration because of their prolonged treatment duration and propensity to rapidly progress, resulting in severe complications. The primary challenge in their treatment stems from the involvement of drug-resistant microorganisms that can form impermeable biofilms, as well as the possibility of infection extending deep into tissues, thereby complicating drug delivery. Dissolving microneedle patches are an innovative transdermal drug-delivery system that effectively enhances drug penetration through the stratum corneum barrier, thereby increasing drug concentration at the site of infection. They offer highly efficient, safe, and patient-friendly alternatives to conventional topical formulations. This comprehensive review focuses on recent advances and emerging trends in dissolving-microneedle technology for antimicrobial skin-infection therapy. Conventional antibiotic microneedles are compared with those based on emerging antimicrobial agents, such as quorum-sensing inhibitors, antimicrobial peptides, and antimicrobial-matrix materials. The review also highlights the potential of innovative microneedles incorporating chemodynamic, nanoenzyme antimicrobial, photodynamic, and photothermal antibacterial therapies. This review explores the advantages of various antimicrobial therapies and emphasizes the potential of their combined application to improve the efficacy of microneedles. Finally, this review analyzes the druggability of different antimicrobial microneedles and discusses possible future developments.