Microneedle Patch Research Articles

Double-Layered Microneedle Patch Integrated with Multifunctional Nanoparticles and Live Bacteria for Long-Term Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a complex and prevalent chronic inflammatory skin disease that impacts a significant portion of the global population. Conventional treatments often focus on a singular pathogenic factor or suffer from limited skin penetration, resulting in unsatisfactory outcomes. Here, a multifunctional double-layered microneedle (MN) patch is proposed for long-term and effective treatment of AD by integrating therapeutic nanoparticles (NPs) and live bacteria. In the design, the MN tips are loaded with Prussian blue NPs encapsulating cetirizine hydrochloride (CET@PB NPs), while the patch backing incorporates Bacillus subtilis (B. subtilis). Upon skin insertion, the MN patch efficiently delivers CET@PB NPs into the skin and deposits live B. subtilis on the skin surface after fast dissolution. The delivered NPs not only scavenge reactive oxygen species (ROS) and improve oxidative stress microenvironments in the AD lesions, but also provide sustained release of the antihistamine CET in the skin for alleviating AD symptoms. Furthermore, B. subtilis survives on the skin for over 9 days and effectively inhibits the growth of the harmful bacteria Staphylococcus aureus. These features highlight the superior efficacy of the MN patch in long-term treatment of AD, offering a promising alternative for the management of skin disorders in clinics.

Multifunctional Microneedle Patches for Perivascular Gene Delivery and Treatment of Vascular Intimal Hyperplasia.

Gene therapy has emerged as a promising approach to address challenging cardiovascular diseases. Extensive efforts have been focused on developing highly efficient gene vectors with precise delivery techniques to enhance its effectiveness. In this study, we present multifunctional dopamine-gelatin microneedle patches with gene therapy capabilities to achieve perivascular gene delivery for intimal hyperplasia treatment. These patches that were fabricated through freeze-drying of gelatin are with recombinant adeno-associated virus (rAAVs)-carrying tips and dopamine coating backing layers. The lyophilized gelatin could not only effectively preserve the therapeutic activity of rAAVs but could also demonstrate the capability to penetrate the adventitia for efficient delivery. The incorporation of dopamine facilitated patch adhesion and extended the release duration. Based on these advantages, we have demonstrated that the rAAVs-loaded microneedle patches (AMNPs) behave satisfactorily in perivascular gene delivery to inhibit carotid artery restenosis in rats. These features indicate that the AMNPs are clinically valuable in the treatment of vascular intimal hyperplasia diseases.

Piperine‐Loaded Sodium Caseinate Nanoglobules Delivered Transdermally Through Microneedle Patch for Improved Bioavailability at Adipose Tissue

ABSTRACTDespite being a well‐known anti‐obesity chemical, piperine has only found limited therapeutic use because of its poor bioavailability at the site of action. In order to test this hypothesis, we placed piperine sodium caseinate nanoglobules (PSN) in microneedle patches (MNPs), which may enhance piperine transdermal delivery and absorption. Clove oil, sodium caseinate to make nanoglobules, and PEG 400 as a stabilizer were used in a nanoglobules process to create the PSN. The polydispersity index (0.256) and particle size (134.4 nm) of the developed PSN were both smaller, while their zeta potential (−44.4 mV) and encapsulation efficiency (90%–95%) were both greater. Compared to native piperine, the PSN increased solubility, bioaccessibility (6.5 times), and bioavailability (2.8 fold). Moreover, the PSN‐loaded MNPs were created using the micro‐molding (poly‐dimethylsiloxane (PDMS) mold) approach. In both PBS buffer and porcine skin, the PSN‐loaded MNPs were rapidly hydrolyzed, with 50% piperine release in less than 5 min. Also, the produced MNPs demonstrated improved bioavailability of piperine in the plasma (180 ng/mL) and adipose (425 ng/mL) tissue of C57BL6 mice. In conclusion, the work offered a theoretical foundation for utilizing new PSN‐loaded MNPs as a viable piperine delivery method for treating obesity.

Microneedle patches incorporating zinc-doped mesoporous silica nanoparticles loaded with betamethasone dipropionate for psoriasis treatment.

Treating psoriasis presents a major clinical challenge because of the limitations associated with traditional topical glucocorticoid therapy. This study introduced a drug delivery system utilizing zinc-doped mesoporous silica nanoparticle (Zn-MSN) and microneedle (MN), designed to enhance drug utilization for prolonged anti-inflammatory and anti-itch effects. The MN system facilitated the transdermal delivery of betamethasone dipropionate (BD), allowing its slow release. The BD@Zn-MSN-MN system promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype, achieving superior anti-inflammatory effects compared to the clinically used BD cream. Additionally, this study demonstrated that BD@Zn-MSN-MN could further alleviate itching in psoriasis-afflicted mice by decreasing the excitability of the transient receptor potential vanilloid V1 (TRPV1) ion channel positive neurons and reducing the release of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). These findings offer new insights and effective therapeutic options for the future design of transdermal drug delivery for psoriasis.

Prevention of early thrombosis in transplanted vein model by encapsulation with tirofiban microneedle drug delivery system.

Early thrombosis following CABG surgery leads to perioperative myocardial infarction, which causes difficulties for clinicians and patients. Moreover, once perioperative myocardial infarction occurs, the mortality rate is extremely high. In recent years, microneedle (MN) drug delivery systems have become a research hotspot with broad clinical application prospects. These systems are capable of achieving sustained, safe, and painless local drug release. In cardiovascular applications, MNs maximize local anticoagulant effects, inhibit endometrial hyperplasia, and reduce systemic side effects. We speculate that a MN drug delivery system can be used to target transplanted veins to inhibit their thrombosis and reduce the incidence of perioperative myocardial infarction after CABG surgery. Therefore, this study developed a hyaluronic acid MN patch loaded with tirofiban and conducted preliminary physicochemical tests. The safety, efficacy, biocompatibility, and targeting of the MN system were evaluated using in vitro and in vivo experiments using a jugular vein transplantation model. The results indicate that the MN system has excellent physical properties, safety, effectiveness, biocompatibility, and strong targeting, which can effectively inhibit early local thrombus formation. In addition, the observation of early postoperative endometrial hyperplasia activation provides a foundation for future research.&#xD.

Transdermal Delivery of Superoxide Dismutase Using Polymeric Microneedle Patches to Inhibit Skin Aging

AbstractSkin aging is characterized by a deterioration of skin quality over time resulting from physiological changes and oxidative stress (OS). Superoxide dismutase (SOD) is an effective antioxidant enzyme widely used as a food supplement and cosmetic additive to alleviate OS and retard skin aging. However, conventional SOD delivery routes commonly yield unsatisfactory results due to limited stability, compromised bioavailability, and low absorption efficiency in the gastrointestinal (GI) tract. These issues are addressed by developing SOD‐encapsulated polymeric microneedle (PMN) patches for efficient transdermal delivery. The use of a highly stable SOD isolated from a hot spring microbe ensures its reactivity throughout PMN fabrication and application. This SOD vehicle demonstrated excellent effectiveness through inhibiting skin‐aging and promoting hair growth as validated by extensive in vivo experiments using D‐galactose (D‐gal) induced aging‐mouse model. SOD‐PMNs promoted excellent regeneration of hair follicles, increased melanin synthesis, decreased lipid oxidation, and elevated antioxidative capacity of skin tissue. The success in effective transdermal delivery of SOD promises wide applicability in pharmaceutical and cosmetic industries.

Development and Validation of RP-HPLC Method for Quantification of Resveratrol in a Resveratrol-Solid Lipid Nanoparticles Loaded Microneedles Patch

Development and Validation of RP-HPLC Method for Quantification of Resveratrol in a Resveratrol-Solid Lipid Nanoparticles Loaded Microneedles Patch

Living photosynthetic microneedle patches for in situ oxygenation and postsurgical melanoma therapy.

Surgical excision remains the principal treatment for melanoma, while tumor recurrence and delayed wound healing often occur due to the residual tumor cells and hypoxic microenvironment in the postoperative skin wounds. Herein, we present a living photosynthetic microneedle (MN) patch (namely MA/CM@MN) loaded with microalgae (MA) and cuttlefish melanin (CM) for postsurgical melanoma therapy and skin wound healing. Benefiting from the oxygenic photosynthesis of the alive MA in the MN base, the MA/CM@MN can generate oxygen under light exposure, thus facilitating skin cell proliferation and protecting cells against hypoxia-induced cell death. In addition, with CM nanoparticles embedded in the MN tips, the MA/CM@MN can be effectively heated up under near-infrared (NIR) irradiation, contributing to a strong tumor killing efficacy on melanoma cells in vitro. Further experiments demonstrate that the NIR-irradiated MA/CM@MN effectively prevents local tumor recurrence and simultaneously promotes the healing of tumor-induced wounds after incomplete tumor resection in melanoma-bearing mice, probably because the MA/CM@MN can inhibit tumor cell proliferation, stimulate tumor cell apoptosis, and mitigate tissue hypoxia in light. These results indicate that the living photosynthetic MN patch offers an effective therapeutic strategy for postoperative cancer therapy and wound healing applications.

An Integrated Therapeutic Nanoparticles and Quorum Quenching‐Based Microneedle Patch for Bacterial‐Infected Wound Healing

AbstractSkin injuries leading to drug‐resistant bacterial infections remain a significant challenge, posing a threat to human health. There is an urgent necessity to develop wound dressings for the treatment of such injuries. The proceeding study presents the design of a multifunctional microneedle (MNs) patch containing quorum‐quenching enzyme and manganese dioxide (MnO2) nanoparticles for treating Pseudomonas aeruginosa‐infected wounds. In co‐culture experiments with P. aeruginosa, the quorum‐quenching enzyme significantly reduced the production of virulence factors and inhibited biofilm formation. MnO2 NPs exhibited excellent scavenging ability against a wide range of free radicals when assayed in in vitro antioxidant assays. Subsequently, soluble hyaluronic acid is chosen as the substrate in order to prepare the MNs patches loaded with quorum quenching enzyme and MnO2 NPs for wound healing assessment in a P. aeruginosa‐infected mouse wound model. Evaluation of wound size and closure rate demonstrated that the patch significantly accelerated wound healing, resulting in shorter healing durations and improved wound closure. Additionally, inflammation‐related cytokine levels are reduced, indicating a lower level of inflammation. Tissue section staining shows that treatment with MNs promoted wound epithelialization, collagen deposition, and angiogenesis. The multifunctional MNs patch represents a promising treatment option for drug‐resistant bacterial infections in wound management.

Microneedle‐Loaded Gene‐Editable Nanohybrids Engineer Cancer Cells by Telomere Stress Induction and Metabolic Interference for Enhanced Cuproptosis and Immunotherapy

AbstractCuproptosis, a novel copper‐driven cell death, offers potential for cancer therapy, yet challenges persist in targeted delivery of copper ions and therapeutic resistance management. Here, CuTG‐Cas9@PLL, a cuproptosis nano‐inducer for efficient delivery of Cu ions, 6‐Thio‐dG (6‐thio‐2′‐deoxyguanosine), and CRISPR/Cas9 to enhance cuproptosis and immunotherapy via telomere stress and metabolic interference is developed. This system, combined with microneedle patches for transdermal delivery in melanoma treatment, targets the “Warburg effect,” a key resistance mechanism, through CRISPR/Cas9‐mediated LDHA knockout, thereby sensitizing cancer cells to cuproptosis and reversing immune suppression. Moreover, 6‐Thio‐dG‐induced telomere stress not only amplifies cuproptosis via autophagy dysfunction but also boosts anti‐tumor immunity by increased immunogenicity of senescent cancer cells. This work presents a novel approach for developing efficient cuproptosis nano‐inducers and reports on the feasibility of enhancing cancer cuproptosis and anti‐tumor immunotherapy through telomere stress induction and CRISPR/Cas9‐mediated metabolic interference.

FABRICATION AND CHARACTERIZATION OF DISSOLVING MICRONEEDLE PATCH USING 3D PRINTED MASTER

Objective: The purpose of this study was to fabricate a dissolving microneedle patch using a 3D-printed master and characterize it using various techniques. Methods: Dissolving microneedle patches were developed using Computer-Aided Design (CAD) software and 3D printing. Polydimethylsiloxane (PDMS) reverse molds were cast from the 3D-printed masters and filled with a solution of 20% Chitosan Oligosaccharide (COS) and 20% Polyvinyl Alcohol (PVA). The patches were dried at room temperature and characterized using Scanning Electron Microscopy (SEM), Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), X-ray diffraction (XRD), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and in vitro skin penetration studies. Results: Optical microscopy and SEM images showed the formation of a uniform microneedle. The peak at 1248 cm⁻¹ in the ATR-FTIR spectrum indicates the formation of cross-links between certain PVA radical groups and COS. XRD revealed that both polymers blended well and showed partial crystallinity, with peaks at 2θ = 11.39°, 2θ = 20°, and 2θ = 41°. DSC and TGA analyses revealed that the blend could withstand high temperatures with good stability at temperatures up to 200 °C. In vitro skin penetration studies confirmed that microneedles could successfully penetrate the skin, indicating their potential for effective transdermal drug delivery. Conclusion: This study demonstrated that COS/PVA dissolving microneedles fabricated using 3D printing and micro-molding have significant potential for transdermal drug delivery.

A Smartphone-Enabled Colorimetric Microneedle Sensing Platform for Rapid Detection of Ascorbic Acid in Fruits.

Achieving rapid extraction and detection of analytical solutions from plant tissues to circumvent cumbersome procedures and reduce the dependence on detection instruments remains a challenge. Herein, a colorimetric microneedle integrated platform was developed for the rapid extraction and detection of plant fluids for testing purposes. Colorimetric microneedle patches (CMPs) offer a swift and effective method to swiftly extract and detect ascorbic acid (AA) within 10 min from various fruit crops like mango, nectarine, apple, pear, and kiwifruit, facilitated by a smartphone application. CMPs are constructed for the rapid and sensitive analysis of AA with good linearity amid the range 0.05-25 μM and a low limit of detection of 30 nM. The novel CMPs demonstrate significant potential as a rapid detection platform for AA in plants. CMPs offer significant advantages over traditional ultraviolet spectrophotometry, such as simplified operational procedures and accelerated extraction and detection processes. This establishes robust groundwork for conducting in situ extraction and molecular detection of diverse crops across a spectrum of application scenarios.

Development of a novel hyaluronic acid/alginate/RANKL degradable microneedle patch for accelerating bone remodeling and orthodontic tooth movement through promoting osteoclastogenesis

The prolonged duration of orthodontic treatment remains a significant concern for both orthodontists and patients. In this study, we developed a degradable microneedle (MN) patch composed of hyaluronic acid (HA) and sodium alginate (SA) for the delivery of receptor activator of nuclear factor-kappa B ligand (RANKL) to accelerate tooth movement. This MN patch which was crosslinked by calcium chloride (CaCl2) exhibits adequate mechanical properties and favorable in vitro mucosal insertion ability. Moreover, the MN patch can achieve the sustained release of RANKL and maintain the biological stability of RANKL protein after one month of storage at −20 °C, 4 °C, or 37 °C. In vitro experiments using RAW264.7 cells indicated that the HA/SA/RANKL MN possessed excellent biocompatibility and could effectively induce osteoclast differentiation. In vivo application of the HA/SA/RANKL MN in rat models showed a remarkable effect in promoting osteoclast formation and accelerating tooth movement. These findings suggest that the degradable HA/SA/RANKL MN holds significant potential for enhancing tooth movement efficiency.

Microneedles based on hyaluronic acid-polyvinyl alcohol with antibacterial, anti-inflammatory, and antioxidant effects promote diabetic wound healing

Diabetic wound healing has become one of the major clinical burdens due to uncontrolled bacterial growth and an increase in the risk of various microbial infections. Despite excellent antioxidant properties, the poor aqueous solubility of resveratrol (RES) hampers its applicability. In this study, we proposed a novel multifunctional microneedle patch loaded with RES-encapsulated polymeric micelles. Resveratrol micelles (RES MC) were loaded in the microneedle tip, while the base part was coated with the antibiotic gentamicin (GEN) to promote wound healing. The microneedle tip composed of sodium hyaluronate (HA) could effectively deliver the anti-inflammatory and antioxidant RES MC. Furthermore, the base of the microneedle patch composed of polyvinyl alcohol (PVA) offered excellent flexibility, releasing GEN and providing resistance to bacterial contamination, thereby further promoting wound repair. In vitro antibacterial experiments indicated that the bactericidal rate reached 99 %. Further, the wound healing rate was recorded as 86.05 % on the 11th day of diabetes wound treatment. Together, the multifunctional microneedle patch with excellent biocompatibility exhibited anti-inflammatory, antioxidant, and antibacterial effects on the wound healing process, potentiating its efficacy in the treatment of diabetic wounds.

Efficient extraction of interstitial fluid using an ultrasonic-powered replaceable hexagram-shaped hydrogel microneedle patch for monitoring of dermal pharmacokinetics and psoriatic biomarkers

Monitoring biomarkers and pharmacokinetics is crucial for the precise diagnosis and treatment of chronic skin diseases. Dermal interstitial fluid (ISF) presents an attractive alternative source of biomarkers and drugs to blood; however, a simple, efficient, and comfortable extraction method is lacking. Here, we combine high-precision 3D printing and micromolding to develop an ultrasonic-powered, replaceable hexagram-shaped hydrogel microneedle (HMN) patch. Hexagram-shaped HMNs exhibit superior mechanical strength and faster ISF extraction rates compared to cone, pyramid, and octagram shapes. The patch, attached to a holder and integrated with a commercial ultrasonic device via a customized connector, allows easy replacement after use. With ultrasound assistance, the patch extracts over 15 μL, 6 μL, and 4 μL of ISF from porcine skin ex vivo, healthy mouse skin, and psoriatic mouse skin in vivo, respectively, within 1 min. The recovered ISF, obtained via centrifugation from HMNs, is used to monitor the dermal pharmacokinetics of drugs (e.g., methotrexate) and psoriasis-related biomarkers (e.g., interleukin-17 and –22) in mouse models, showing trends comparable to those detected via skin biopsy and blood draw. This ultrasonic-powered, replaceable hexagram-shaped HMN patch holds great promise for advancing the diagnosis, treatment, and research of skin diseases.

A dissolving microneedle patch loaded with plumbagin/hydroxypropyl-β-cyclodextrin inclusion complex for infected wound healing

Treating infected wounds is facing a serious challenge due to the rapid spread of antibiotic resistance worldwide. In the search for novel antimicrobial drugs, natural products often serve as a crucial resource. Plumbagin (PLB) is the most important natural active ingredient in the root of Plumbago zeylanica L. known for its excellent antibacterial ability. However, the application of PLB is limited because of its poor water solubility, instability, and tendency to sublimate. In this study, we propose a solution by designing a hyaluronic acid (HA)/polyvinylpyrrolidone (PVP) dissolving microneedle patch loaded with PLB/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex. PLB was encapsulated into the cavity of HP-β-CD to improve its solubility and stability using the neutralization agitation method. The formation of the inclusion complex significantly increased the water solubility of PLB to 1350 ± 6.8 μg/mL, which is 17 times higher than its original value of 79.3 ± 1.7 μg/mL. The encapsulation efficiency was found to be 94.82 ± 3.34%. In vitro drug release studies, PLB microneedles loaded with PLB/HP-β-CD inclusion complex rapidly released into PBS within 15min. Furthermore, the PLB microneedles exhibited strong antibacterial activity against Staphylococcus aureus (S. aureus) both in vivo and in vitro. They also remarkably accelerated the healing of infected wounds in mice by enhancing collagen deposition and re-epithelialization, reducing inflammation, and stimulating angiogenesis. Overall, this multifunctional microneedle patch shows promising potential for clinical applications in the healing of infected wounds.

An Aptamer-responsive Microneedle Patch Sensor Platform Combining with Hybridization Chain Reaction Amplification for Detection of Steroid Hormone Cortisol in Skin Interstitial Fluid

An Aptamer-responsive Microneedle Patch Sensor Platform Combining with Hybridization Chain Reaction Amplification for Detection of Steroid Hormone Cortisol in Skin Interstitial Fluid

Dual-Action Psoriasis Therapy: Antiproliferative and Immunomodulatory Effects via Self-Locking Microneedles.

Psoriasis is a chronic, immune-mediated disorder characterized by immune regulation disorders and abnormal keratinocyte proliferation. Deucravacitinib (Deu), a selective oral Tyrosine Kinase 2 (TYK2) inhibitor, shows promise in treating psoriasis but may cause systemic side effects and fail to address persistent localized thickened lesions. Herein, a self-locking microneedle (MN) patch with a polyvinyl alcohol (PVA) inner ring loaded with Deu is developed, designed to penetrate the transdermal barriers and dissolve rapidly, downregulating the IL-23/IL-17 pathway and serve as the first line of defense against the spread of skin-originated inflammation. Additionally, Calcipotriol (Cal), a vitamin D derivative, is incorporated into a methacrylated hyaluronic acid (HAMA) backing layer and outer ring that mimics occlusive administration, maintaining localized skin surface retention for prolonged anti-proliferative therapy. The Deu@Cal MN demonstrates satisfactory adhesiveness due to swelling-mediated mechanical interlocking via the outer ring, ensuring targeted drug release at lesion site. Besides its effectiveness in alleviating both skin inflammation and proliferation, it inhibits the differentiation of Th17 cells in the spleen, suggesting potential to reduce systemic inflammation. These findings offer a new therapeutic approach for treating psoriasis and other autoimmune and inflammatory conditions.

Transdermal insulin delivery via microneedle technology, patches, and pumps offers a promising alternative to traditional subcutaneous injections for diabetes management

Transdermal insulin delivery via microneedle technology, patches, and pumps offers a promising alternative to traditional subcutaneous injections for diabetes management

Melanin Hydrogel Inverse Opal Microneedle Patches for Wound Healing.

Bacterial infected wounds bring an economic burden to the worldwide medical care field. A variety of bioactives-integrated hydrogel patches are developed in response to this challenge. Here, the melanin hydrogel inverse opal microneedle patches (MNs) with antioxidant and visual color sensing abilities for the management of bacterial infected wounds are proposed. The MNs are fabricated by applying melanin-loaded polyethylene glycol diacrylate (PEGDA) as the inverse opal hydrogel and using bacitracin-carried gelatin to fill those nanopores of hydrogel scaffold. Benefitting from the antioxidant capacity of melanin nanoparticles and the local antimicrobial ability of bacitracin, the resulting MNs possess the integrated functions of reactive oxygen species scavenging and antibacterial. Besides, the inverse opal structure endows the MNs with vivid structure color and detectable reflected wavelength, which can gradually shift with the release of the drug, thus allowing MNs to assess the drug delivery. Based on these characteristics, MNs perform excellent in in vitro drug delivery and monitoring, as well as the promotion of bacterial infected wound recovery in vivo, indicating the potential of MNs in the future wound management field.