Microneedle Patch Research Articles

MPatch: a wearable hydrogel microneedle patch for in vivo optical sensing of calcium.

This study presents an in vivo optical hydrogel microneedle platform that measures levels of analytes in interstitial fluid. The platform builds on a previously published technique for molding hydrogel microneedles by developing a composite hydrogel (i.e., PEGDA and polyacrylamide) that is sufficiently stiff to penetrate skin in the hydrated state and whose fluorescence changes dynamically-via a conjugated aptamer-depending on level of analyte. In a demonstration relevant to hypercalcemia, the hydrogel microneedle distinguished varying concentrations of calcium (within a range of 0 to 2 mM, which spans physiologically meaningful variations for hypoparathyroidism) within 10 minutes. In rats, a compact CMOS sensor measuring fluorescence from microneedles distinguished low hypercalcemic (1.7 mM) from high hypercalcemic (2.3 mM) ionized calcium levels as determined from reference blood measurements. Overall, this work demonstrates in vivo feasibility of a concept-which we call mPatch-for an optical hydrogel microneedle to measure small changes in levels of analytes in interstitial fluid, which does not rely on extraction of interstitial fluid out of the dermis.

Liposome-loaded dissolvable microneedle patches for more efficient intradermal antigen delivery of Hepatitis B vaccine

The aim of this study was to improve the efficacy of Hepatitis B surface antigen (HBsAg) vaccination via liposome-loaded dissolvable microneedle (Lipo-dMN) patches. HBsAg liposomes were prepared using the thin-film hydration method and subsequently incorporated into dissolvable microneedle patches via a pre-vacuum approach. Liposomes, dissolvable microneedle patches (dMN), and Lipo-dMN were characterized for encapsulation efficiency, mechanical properties, morphology, skin insertion, in vitro release, cellular uptake, and in vivo vaccination studies. The HBsAg was encapsulated into liposomes with encapsulation efficiencies around 50 %, particle size around 160 nm, and zeta potential around −20 mV. HBsAg can maintain its activity during the preparation of dMN and Lipo-dMN. The intact pyramid microneedle has a sharp end and strong mechanical properties that allow easy insertion into the ex vivo pig skin. The dMN and Lipo-dMN, with a mechanical property of 1.6 N, readily penetrate the epidermis and release the HBsAg and HBsAg liposome to modulate the immune response. A comprehensive comparison of HBsAg subcutaneous injection and intradermal delivery of HBsAg and HBsAg liposome by dMN revealed different levels of anti-HBsAg IgG antibody. Inoculation with dMN and Lipo-dMN resulted in significantly higher levels of anti-HBsAg IgG antibodies (p < 0.01) compared to subcutaneous injection of HBsAg. In addition, we found that IgG levels increased significantly (P < 0.05) with increased dose of subcutaneous injection of HBsAg and intradermal delivery of dMN, but the opposite effect was observed in Lipo-dMN. The possible mechanism for this observation may be the increased cellular uptake of liposomes by BMDCs upon long-term incubation. In summary, this study presents a promising approach to enhance HBsAg vaccination efficacy through the synergistic combination of liposomes and dissolvable microneedles at reduced vaccine doses.

Anti-obesity effect of resveratrol-loaded dissolving microneedle patch: In vitro and in vivo studies

Anti-obesity effect of resveratrol-loaded dissolving microneedle patch: In vitro and in vivo studies

Vaccination in hemophilic children: Challenges, innovations, and future directions

Introduction: Hemophilia, an inherited disorder primarily affecting blood clotting due to deficiencies in clotting factors VIII or IX, presents complex challenges for vaccination. Children with hemophilia require vaccinations to prevent infections that may exacerbate their bleeding disorder. However, traditional intramuscular vaccination poses bleeding risks, necessitating specialized administration methods and careful post-vaccination care. Purpose: This study examines the efficacy and safety of vaccination in pediatric hemophilia patients, emphasizing the importance of individualized protocols to manage bleeding risks effectively. It explores recent advancements, including needle-free technologies, the potential of gene therapy, and mRNA vaccines. Materials and Methods: The study synthesizes current guidelines from global health organizations, hemophilia management protocols, and clinical studies on vaccine safety in hemophilia. It highlights techniques such as subcutaneous administration, clotting factor prophylaxis, and the use of fine-gauge needles to minimize bleeding complications. Results: Findings indicate that with appropriate management, hemophilic children achieve adequate immune responses to vaccines, with reduced bleeding risks. Emerging technologies, such as microneedle patches, jet injectors, and gene therapy, offer promising safer vaccination alternatives. Additionally, mRNA vaccines demonstrate strong immunogenicity without the need for live-virus vectors, reducing complication risks. Conclusions: Vaccination, when adapted to hemophilia-specific needs, remains essential for infection prevention in this vulnerable population. Newer vaccine technologies and individualized care protocols enhance safety and efficacy, contributing to improved quality of life and long-term health outcomes for hemophilic children.

Potency chitosan-based microneedle Parem patch with Zingiber zerumbet l. Extract in inhibiting pro-inflammatory (TNF-α and IL-1β) in arthritis

Arthritis is a condition that affects the joints, and it is caused by the production of proinflammatory cytokines and leading to discomfort in patients. According to the latest data from the Centers for Disease Control, in 2021 global incidence of arthritis over the past five years reached over 53.2 million. On the other hand, several studies have found that long-term use of arthritis medications can have side effects. This study aimed to investigate the effect of using microneedle parem patch in inhibiting proinflammatory factors, particularly for TNF-α and IL-1β. The experimental study is divided by three group, normal control, negative control, positive control, and microneedle patch. Patch was tested by in vivo in the form of rats injected with MIA (monosodium iodoacetate) and it was found that the microneedle parem patch could inhibit proinflammatory cytokine production (TNF-α and IL-1β) with an inhibition percentage of 30.01% for TNF-α and 70.99% for IL-1β. Therefore, it can be concluded that the microneedle parem patch can inhibit proinflammatory cytokine production (TNF-α and IL-1β) in arthritis.

A wearable osmotic microneedle patch provides high-capacity sustained drug delivery in animal models.

The maintenance of stable plasma drug concentrations within a therapeutic window can be critical for drug efficacy. Here, we developed a wearable osmotic microneedle (OMN) patch to support sustained drug dosing for at least 24 hours without the use of electronic components. The OMN patch uses an osmotic pressure driving force to deliver drug solution into the skin through three hollow microneedles with diameters of less than 200 micrometers. The rate of drug release was related to the composition and concentration of the osmogen and drug and to the physical properties of the semipermeable membrane separating the low- and high-solute compartments. The OMN patch released the peptide drug exenatide in rats and mice for 24 hours, whereas subcutaneous injection resulted in a burst release and rapid decline in the plasma drug concentration. OMN release of exenatide improved glycemic control in a diabetic mouse model consistent with a sustained effective plasma concentration of the drug. Continuous release of the small-molecule chemotherapeutic drug cytarabine reduced the progression of acute myeloid leukemia in mice more effectively than subcutaneous injection. Further evaluation of the OMN patch in canines demonstrated continuous dosing of cytarabine up to 225 milligrams for 24 hours, satisfying clinical requirements (150 to 300 milligrams daily). OMN patches were well tolerated in human participants with minimal pain or irritation of the skin and a stated preference over other administration routes. This wearable drug delivery system could provide a platform for stable high-dose drug release with convenience and safety.

Vaccines in the Era of Emerging Infectious Diseases: Immune Mechanisms and Innovations

Emerging infectious diseases (EIDs) continue to challenge global public health, driven by factors like climate change, urbanization, and increasing human-animal interactions. The rapid spread of the COVID-19 pandemic highlighted the need for swift vaccine development and deployment. Vaccines remain one of the most effective public health tools, capable of preventing disease outbreaks by inducing immunity through humoral and cell-mediated mechanisms. Recent advancements in immunology and biotechnology have revolutionized vaccine development, enabling the creation of new platforms such as mRNA vaccines, viral vectors, and nanoparticle-based vaccines. These innovations allow for faster production, greater efficacy, and adaptability to novel pathogens. Additionally, new delivery methods, including microneedle patches and nasal sprays, aim to improve accessibility and ease of administration, particularly in low-resource settings. However, challenges such as vaccine equity, distribution logistics, and public hesitancy must be addressed to ensure broad and effective vaccination coverage. This review explores the immune mechanisms of vaccines, current vaccine technologies, and emerging innovations to address EIDs, with a focus on future preparedness for pandemics. Keywords: Emerging infectious diseases, vaccines, mRNA technology, nanoparticle vaccines, immune mechanisms, vaccine innovations

Novel microneedle patches for transdermal delivery of AP39, a hydrogen sulphide donor, in the treatment of scenarios mimicking neurological disorders

Novel microneedle patches for transdermal delivery of AP39, a hydrogen sulphide donor, in the treatment of scenarios mimicking neurological disorders

Light-responsive antibacterial dissolving microneedles loaded with 5-aminolevulinic acid and silver nanoparticles for the treatment of acne

Acne is a chronic inflammatory disease of pilosebaceous unit, which can be aggravated by hyperkeratosis of the pilosebaceous unit, excessive secretion of sebum and the proliferation of Propionibacterium acnes (P. acnes). Traditional drug treatment methods commonly exhibit drawbacks, including bacterial resistance and poor transdermal permeability, resulting in suboptimal efficacy and recurrent infections. Herein, we designed a dual drug-loaded microneedles patch to deliver ALA and silver nanoparticles for acne treatment. The comprehensive treatment of acne is achieved by utilizing the safe and efficient advantages of 5-aminolevulinic acid (ALA) photodynamic therapy (PDT), coupled with the superior antibacterial properties of silver nanoparticles. To enhance drug permeability, dissolving microneedles (DMNs) are employed for targeted and efficient drug delivery. In vitro and in vivo experiments demonstrated that DMNs loaded with both AgNPs and ALA-PDT (ALA/AgNPs@DMNs) have significant antibacterial activity, along with superior drug loading capacity and penetration. The application of ALA/AgNPs@DMNs in treating acne-affected rats alleviates excessive epidermal keratinization, effectively inhibits bacterial growth, and significantly improves acne symptoms. This suggests that the “dissolving microneedle” formulation holds promise for the treatment and management of acne.

Ultrasound-Responsive Carbon Monoxide Microneedle for Enhanced Healing of Infected Diabetic Wounds.

Efficient management of difficult-to-heal diabetic wounds remains a clinical challenge owing to bacterial infections, as well as oxidative and hyperglycemic complex pathology. Therefore, developing intelligent strategies for diabetic wound healing is urgently needed. Herein, an ultrasound (US)-responsive microneedle (MN) patch (MN@GOX@TiO2-X@CO) capable of controlled delivery of carbon monoxide (CO) gas within the skin for effective treatment of diabetic infected wounds is developed. Benefiting from the specific form of microneedle (MN) patch, sonosensitizer (TiO2-X), •OH-responsive CO prodrug (MPA-CO), and glucose oxidase (GOX) can be loaded together and effectively delivered to infectious wounds. With the semi-fluidic hyaluronic acid (HA) coating under the physiological condition, CO could be released efficiently in situ and directly acted on infected wound tissue upon US triggering. Both in vitro and in vivo results showed that US-triggered CO release from MN@GOX@TiO2-X@CO not only effectively inhibited the S. aureus and MRSA infection but also promoted fibroblasts proliferation and migration under hyperglycemic physiology, thereby accelerating diabetic wound healing. Collectively, the approach effectively addresses the impaired skin regeneration function in diabetic wounds and offers a promising therapeutic strategy for the efficient healing of infected diabetic wounds.

Stimulation of microneedles alleviates pathology of Parkinson's disease in mice by regulating the CD4+/CD8+ cells from the periphery to the brain.

Immune dysfunction is a major cause of neuroinflammation and accelerates the progression of Parkinson's disease (PD). Numerous studies have shown that stimulation of specific acupuncture points (acupoints) can ameliorate PD symptoms. The purpose of this study was to investigate whether attaching microneedles to acupoints would improve PD pathology by recovering immune dysfunction. The PD mouse model was induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA), and microneedle patches (MPs) or sham patches (SPs) were attached to GB20 and GB34, representative acupoints for treating PD for 14 days. First, the behavioral experiment showed that motor disorders induced by 6-OHDA were significantly improved by MP. Simultaneously, 6-OHDA-induced dopaminergic neuronal death and brain neuroinflammation decreased. Conversely, SP had no effect on behavioral disorders, neuronal death, or neuroinflammation. Measurement results from flow cytometry of immune cells in the brain and blood revealed a disruption in the CD4+/CD8+ ratio in the 6-OHDA group, which was significantly restored in the MP group. The brain mRNA expression of cytokines was significantly increased in the 6-OHDA group, which was significantly decreased by MP. Overall, our results suggest that the attachment of MPs to GB20 and GB34 is a new method to effectively improve the pathology of PD by restoring peripheral and brain immune function.

Transdermal delivery of PeptiCRAd cancer vaccine using microneedle patches

Microneedles (MNs) are a prospective system in cancer immunotherapy to overcome barriers regarding proper antigen delivery and presentation. This study aims at identifying the potential of MNs for the delivery of Peptide-coated Conditionally Replicating Adenoviruses (PeptiCRAd), whereby peptides enhance the immunogenic properties of adenoviruses presenting tumor associated antigens. The combination of PeptiCRAd with MNs containing polyvinylpyrrolidone and sucrose was tested for the preservation of structure, induction of immune response, and tumor eradication. The findings indicated that MN-delivered PeptiCRAd was effective in peptide presentation in vivo, leading to complete tumor rejection when mice were pre-vaccinated. A rise in the cDC1 population in the lymph nodes of the MN treated mice led to an increase in the effector memory T cells in the body. Thus, the results of this study demonstrate that the combination of MN technology with PeptiCRAd may provide a safer, more tolerable, and efficient approach to cancer immunotherapy, potentially translatable to other therapeutic applications.

Evaluating the Therapeutic Potential of Microneedle Patch Laser With Multiple Wavelengths in Allergic Rhinitis: Insights From an Allergic Rhinitis Mouse Model.

There is insufficient evidence to determine the effectiveness of treating allergic rhinitis with a patch laser affix to the skin as opposed to direct intranasal irradiation of the nasal mucosa. We aimed to evaluate the effect of the microneedle patch laser with multiple wavelengths in an allergic rhinitis (AR) mouse model and its underlying mechanism. The microneedle patch laser was attached to the skin above the mouse's nasal cavity, transmitting light to the nasal mucosa. For 10 days, the microneedle patch laser administered simultaneous exposure to wavelengths of 670, 780, 850, and 910 nm at either 10 or 20 min each day. Multiple allergic parameters were evaluated following the microneedle patch laser treatment. Microneedle patch laser treatment decreased allergic symptoms and inhibited OVA-specific IgE levels. Additionally, it significantly reduced eosinophil infiltration, epithelial thickness of the nasal mucosa, and IL-4 cytokine levels. The light emitted by the microneedle patch laser attached to the skin, penetrated effectively to the nasal mucosa within the nasal cavity, suggesting potential for treating allergic rhinitis in mice and could be extended in clinical applications.

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.

New biological dressings in diabetic wound healing: Dual effects of anti-infection and immune regulation

Abstract. As a global epidemic, one of the complications of diabetes is chronic difficult heal wounds, especially infectious wounds, which pose a major threat to the quality of life and prognosis of patients. Traditional dressing materials (gauze, film, foam) often have limited effect, and can easily lead to prolonged treatment cycles and antibiotic resistance. In recent years, as an innovative wound management strategy, biological dressings (hydrogels, fiber scaffolds, microneedle patches) have attracted extensive attention due to their antibacterial effect, inhibition of infection, regulation of the body's immune system, promotion of tissue repair, and good biocompatibility. Here, we discuss the impact of diabetes on the body's immune system, tissue cells, and metabolic processes. In addition, we reviewed the specific mechanisms of different biological dressings in the treatment of diabeti-infected wounds. Finally, we discuss current challenges and future research directions.

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.

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