Types Of Microneedles Research Articles

Effect of sequential delivery of 1- and 2-MHz bipolar microneedling radiofrequency energy on thermal tissue reactions in a minipig model.

Bipolar microneedling radiofrequency (RF) treatment generates different patterns of thermal reactions, depending on the skin impedance and RF treatment parameters, including the frequency, power, conduction time, settings of sub-pulse packs, and penetrating depth and type of microneedles used. We compared the effect of sequential delivery of 1- and 2-MHz bipolar RF energy to in vivo minipig skin on thermal tissue reaction. RF treatments at frequencies of 1 and 2MHz were sequentially delivered to minipigs' skin in vivo. A histological study was performed to analyze RF-induced skin reactions at 1-h and at 3-, 7-, and 14-days post-treatment. The skin specimens demonstrated that the two different frequencies of RF treatment generated mixed patterns of the peri-electrode coagulative necrosis (PECN) according to the experimental settings and tissue impedance. In the PECN zone, the tissue coagulation induced by the first RF treatment was surrounded by the effect of the later RF treatment at the other RF frequency. In the inter-electrode non-necrotic thermal reaction zone, the effect of the latter RF treatment was widespread and deep through the dermis, which had received RF treatment at the other frequency first. The delivery of pulsed-type RF energy at sub-pulse packs of 6 or 10 provided effective RF delivery over long conduction time without excessive thermal damage of the epidermis. Nonetheless, by sequential delivery of two different RF frequencies, RF-induced tissue reactions were found to be markedly enhanced. The sequential delivery of 1- and 2-MHz RF energy induces novel histological patterns of tissue reactions, which can synergistically enhance the thermostimulatory effects of each RF setting. Moreover, variations in patterns of tissue reactions can be generated by regulating the order of frequencies and the number of sub-pulse packs of RF used.

Transdermal delivery of iguratimod and colchicine ethosome by dissolving microneedle patch for the treatment of recurrent gout

This study introduces a novel approach of repetitive modeling to simulate the pathological process of recurrent gout attacks in humans. This methodology addresses the instability issues present in rat models of gout, providing a more accurate representation of the damage recurrent gout episodes inflict on human skeletal systems. A soluble nanoneedle system encapsulating colchicine and iguratimod ethosomal formulations was developed. This system aims to modulate inflammatory cytokines and inhibit osteoclast activity, thereby treating inflammatory pain and bone damage associated with recurrent gout. Additionally, a comprehensive evaluation of the microneedles' appearance, morphology, mechanical properties, and penetration capability confirmed their effectiveness in penetrating the stratum corneum. Dissolution tests and skin irritation assessments demonstrated that these microneedles dissolve rapidly without irritating the skin. In vitro permeation studies indicated that transdermal drug delivery via these microneedles is more efficient and incurs lower drug loss compared to traditional topical applications. In vivo pharmacodynamic assessments conducted in animal models revealed significant analgesic and anti-inflammatory effects when both types of microneedles were used together. Further analyses, including X-ray imaging, hematoxylin and eosin (H&E) staining, Safranin-O/fast green staining, tartrate-resistant acid phosphatase staining, and quantification of osteoclasts, confirmed the bone-protective effects of the microneedle combination. In conclusion, the findings of this research underscore the potential of this novel therapeutic approach for clinical application in the treatment of recurrent gout.

Stress factors affecting protein stability during the fabrication and storage of dissolvable microneedles

Abstract Objectives The current review summarizes product and process attributes that were reported to influence protein integrity during manufacturing and storage of dissolvable microneedle arrays. It also discusses challenges in employing established protein characterization methods in dissolvable microneedle formulations. Methods Studies on dissolvable microneedles loaded with protein therapeutics that assess protein stability during or after fabrication and storage were collected. Publications addressing other types of microneedles, such as coated and vaccine-loaded microneedles, are also discussed as they face similar stability challenges. Key findings To date, various researchers have successfully incorporated proteins in dissolvable microneedles, but few publications explicitly investigated the impact of formulation and process parameters on protein stability. However, protein therapeutics are exposed to multiple thermal, physical, and chemical stressors during the fabrication and storage of microneedles. These stressors include increased temperature, shear and interfacial stress, transition to the solid state during drying, interaction with excipients, and suboptimal pH environments. While analytical methods are essential for monitoring protein integrity during manufacturing and storage, the performance of some well-established protein characterization techniques can be undermined by polymer excipients commonly employed in dissolvable microneedle formulations. Conclusions It is essential to understand the impact of key process and formulation parameters on the stability of protein therapeutics to facilitate their safe and effective administration by dissolvable microneedles.

Advances in microneedles for transdermal diagnostics and sensing applications.

Microneedles, the miniaturized needles, which can pierce the skin with minimal invasiveness open up newpossibilities for constructing personalized Point-of-Care (POC) diagnostic platforms.Recent advances in microneedle-based POC diagnostic systems, especially their successful implementation with wearable technologies, enable biochemical detection and physiological recordings in a user-friendly manner. This review presents an overview of the current advances in microneedle-based sensor devices, with emphasis on thebiological basis of transdermal sensing, fabrication, and application of different types of microneedles, and a summary of microneedle devices based on various sensing strategies. It concludes with the challenges and future prospects of this swiftly growing field. The aim is to present a critical and thorough analysis of the state-of-the-art development of transdermal diagnostics and sensing devices based on microneedles, and to bridge the gap between microneedle technology and pragmatic applications.

Polymeric Microneedles for Health Care Monitoring: An Emerging Trend.

Bioanalyte collection by blood draw is a painful process, prone to needle phobia and injuries. Microneedles can be engineered to penetrate the epidermal skin barrier and collect analytes from the interstitial fluid, arising as a safe, painless, and effective alternative to hypodermic needles. Although there are plenty of reviews on the various types of microneedles and their use as drug delivery systems, there is a lack of systematization on the application of polymeric microneedles for diagnosis. In this review, we focus on the current state of the art of this field, while providing information on safety, preclinical and clinical trials, and market distribution, to outline what we believe will be the future of health monitoring.

Innovative freeze-drying technique in the fabrication of dissolving microneedle patch: Enhancing transdermal drug delivery efficiency.

Microneedle patch (MNP) has become a hot research topic in the field of transdermal drug delivery due to its ability to overcome the stratum corneum barrier. Among the various types of microneedles, dissolving microneedles represent one of the most promising transdermal delivery methods. However, the most used method for preparing dissolving microneedles, namely microfabrication, suffers from issues such as long drying time, susceptibility to humidity, and large batch-to-batch variability, which limit the development of dissolving microneedles. In this study, we report for the first time a method for preparing dissolving microneedles using freeze-drying technology. We screened substrates suitable for freeze-dried microneedle patch (FD-MNP) and used coating technology to enhance the mechanical strength of FD-MNP, allowing them to meet the requirements for skin penetration. We successfully prepared FD-MNP using hyaluronic acid as the substrate and insulin as the model drug. Scanning electron microscopy revealed that the microneedles had a porous structure. After coating, the mechanical strength of the microneedles was 0.61N/Needle, and skin penetration rate was 97%, with a penetration depth of 215μm. The tips of the FD-MNP dissolved completely within approximately 60s after skin penetration, which is much faster than conventional MNP (180s). In vitro transdermal experiments showed that the FD-MNP shortened the lag time for transdermal delivery of rhodamine 123 and insulin compared to conventional MNP, indicating a faster transdermal delivery rate. Pharmacological experiments showed that the FD-MNP lowered mouse blood glucose levels more effectively than conventional MNP, with a relative pharmacological availability of 96.59 ± 2.84%, higher than that of conventional MNP (84.34 ± 3.87%), P = 0.0095. After storage under 40℃ for two months, the insulin content within the FD-MNP remained high at 95.27 ± 4.46%, which was much higher than that of conventional MNP (58.73 ± 3.71%), P < 0.0001. In conclusion, freeze-drying technology is a highly valuable method for preparing dissolving microneedles with potential applications in transdermal drug delivery.

The Necessity to Investigate In Vivo Fate of Nanoparticle-Loaded Dissolving Microneedles.

Transdermal drug delivery systems are rapidly gaining prominence and have found widespread application in the treatment of numerous diseases. However, they encounter the challenge of a low transdermal absorption rate. Microneedles can overcome the stratum corneum barrier to enhance the transdermal absorption rate. Among various types of microneedles, nanoparticle-loaded dissolving microneedles (DMNs) present a unique combination of advantages, leveraging the strengths of DMNs (high payload, good mechanical properties, and easy fabrication) and nanocarriers (satisfactory solubilization capacity and a controlled release profile). Consequently, they hold considerable clinical application potential in the precision medicine era. Despite this promise, no nanoparticle-loaded DMN products have been approved thus far. The lack of understanding regarding their in vivo fate represents a critical bottleneck impeding the clinical translation of relevant products. This review aims to elucidate the current research status of the in vivo fate of nanoparticle-loaded DMNs and elaborate the necessity to investigate the in vivo fate of nanoparticle-loaded DMNs from diverse aspects. Furthermore, it offers insights into potential entry points for research into the in vivo fate of nanoparticle-loaded DMNs, aiming to foster further advancements in this field.

Separable and Inseparable Silk Fibroin Microneedles for the Transdermal Delivery of Colchicine: Development, Characterization, and Comparisons.

Colchicine is the first-line option for both the treatment and prophylaxis of gout flares. However, due to potentially severe side effects, the clinical use of colchicine is limited. A well-tolerated and safe delivery system for colchicine is widely desired. For this purpose, colchicine-loaded inseparable microneedles were fabricated using silk fibroin. Additionally, separable microneedles made of silk fibroin as the needle tips and PVP K30 as the base material were developed. Both types of microneedles were evaluated for their mechanical strength, swelling and dissolution characteristics, insertion abilities, degradation properties, in vitro penetration, skin irritation, and in vivo anti-gout effects. The results demonstrated that separable microneedles had greater mechanical strength and insertion ability. Moreover, the separable microneedles separated quickly and caused little skin irritation. In the pharmacodynamic test, mice with acute gouty arthritis responded significantly to treatment with separable microneedles. In conclusion, the separable silk fibroin-based microneedles provide a promising route for colchicine delivery.

Microneedle-Mediated Transdermal Delivery of Genetic Materials, Stem Cells, and Secretome: An Update and Progression.

Medical practitioners commonly use oral and parenteral dosage forms to administer drugs to patients. However, these forms have certain drawbacks, particularly concerning patients' comfort and compliance. Transdermal drug delivery presents a promising solution to address these issues. Nevertheless, the stratum corneum, as the outermost skin layer, can impede drug permeation, especially for macromolecules, genetic materials, stem cells, and secretome. Microneedles, a dosage form for transdermal delivery, offer an alternative approach, particularly for biopharmaceutical products. In this review, the authors will examine the latest research on microneedle formulations designed to deliver genetic materials, stem cells, and their derivatives. Numerous studies have explored different types of microneedles and evaluated their ability to deliver these products using preclinical models. Some of these investigations have compared microneedles with conventional dosage forms, demonstrating their significant potential for advancing the development of biotherapeutics in the future.

Advances in the applications of dissolving polymer microneedles for delivering drugs in ocular diseases

Due to the unique anatomical structure and physiological barriers of the eye, drug delivery for ocular diseases presents a formidable challenge. Conventional methods of ocular drug administration often suffer from limitations such as low drug bioavailability and a lack of tissue targeting, necessitating multiple administrations to achieve the desired therapeutic drug concentrations. In recent years, microneedles, known for their attributes of safety, minimally invasive application, and high efficiency, have found widespread application in ocular drug delivery research. Among the various types of microneedles, dissolving polymer microneedles have emerged as a prominent focus in the field of ocular drug delivery due to their distinct advantages over other microneedle types. This article provides a comprehensive summary and outlook on the progress in the application of dissolving polymer microneedles for drug delivery in ocular diseases.

The Progress in the Application of Dissolving Microneedles in Biomedicine.

In recent years, microneedle technology has been widely used for the transdermal delivery of substances, showing improvements in drug delivery effects with the advantages of minimally invasive, painless, and convenient operation. With the development of nano- and electrochemical technology, different types of microneedles are increasingly being used in other biomedical fields. Recent research progress shows that dissolving microneedles have achieved remarkable results in the fields of dermatological treatment, disease diagnosis and monitoring, and vaccine delivery, and they have a wide range of application prospects in various biomedical fields, showing their great potential as a form of clinical treatment. This review mainly focuses on dissolving microneedles, summarizing the latest research progress in various biomedical fields, providing inspiration for the subsequent intelligent and commercial development of dissolving microneedles, and providing better solutions for clinical treatment.

Preparation and In Vitro Characterization of Microneedles Containing Inclusion Complexes Loaded with Progesterone.

In order to improve patient compliance and the ease of use during progesterone application, and to increase the clinical application of progesterone, progesterone was made into a microneedle. Progesterone complexes were prepared using a single-factor and central composite design. In the preparation of the microneedles, the tip loading rate was used as an evaluation index. The selection of tip materials among the biocompatible materials of gelatin (GEL), hyaluronic acid (HA), and polyvinylpyrrolidone (PVP), and the use of polyvinyl alcohol (PVA) and hydroxypropyl cellulose (HPC) as backing layers, respectively, were carried out and the resulting microneedles were evaluated accordingly. The progesterone inclusion complexes prepared at a molar ratio of 1:2.16 progesterone and hydroxypropyl-β-cyclodextrin (HP-β-CD), a temperature of 50 °C, and reaction time of 4 h had high encapsulation and drug-loading capacities of 93.49% and 9.55%, respectively. Gelatine was finally chosen as the material for the preparation of the micro-needle tip based on the drug loading rate of the tip. Two types of microneedles were prepared: one with 7.5% GEL as the tip and 50% PVA as the backing layer, and one with 15% GEL as the tip and 5% HPC as the backing layer. The microneedles of both prescriptions exhibited good mechanical strength and penetrated the skin of rats. The needle tip loading rates were 49.13% for the 7.5% GEL-50% PVA microneedles and 29.31% for the 15% GEL-5% HPC microneedles. In addition, in vitro release and transdermal experiments were performed using both types of microneedles. The microneedles prepared in this study enhanced the in vitro transdermal amount of progesterone drug by releasing the drug from the microneedle tip into the subepidermis.

Microneedling in the relief of pain in arthritis: a brief review

AbstractPain is the main symptom of arthritis. Microneedling (MN) is a new method of transdermal drug delivery that relieves pain in arthritis according to the mechanisms of pain in arthritis. This paper provides a review of the mechanisms of pain in arthritis and the use of different types of MNs in pain relief in arthritis. The mechanism of pain in arthritis is primarily a joint tissue lesion that causes the release of inflammatory factors by proinflammatory cells, resulting in pain. MNs can carry various drugs to reduce inflammatory factors, cartilage destruction, and thus the symptom of pain. MNs can be classified into 5 types, which are solid MNs, hollow MNs, coated MNs, dissolving MNs, and swelling MNs. Among them, dissolving MNs and swelling MNs have better prospects for application in the long-term management of pain in arthritis due to the biosafety of their materials and the convenience brought by the sustained-release design.

Improved Topical Drug Delivery: Role of Permeation Enhancers and Advanced Approaches.

The delivery of drugs via transdermal routes is an attractive approach due to ease of administration, bypassing of the first-pass metabolism, and the large skin surface area. However, a major drawback is an inability to surmount the skin's stratum corneum (SC) layer. Therefore, techniques reversibly modifying the stratum corneum have been a classical approach. Surmounting the significant barrier properties of the skin in a well-organised, momentary, and harmless approach is still challenging. Chemical permeation enhancers (CPEs) with higher activity are associated with certain side effects restricting their advancement in transdermal drug delivery. Furthermore, complexity in the interaction of CPEs with the skin has led to difficulty in elucidating the mechanism of action. Nevertheless, CPEs-aided transdermal drug delivery will accomplish its full potential due to advancements in analytical techniques, synthetic chemistry, and combinatorial studies. This review focused on techniques such as drug-vehicle interaction, vesicles and their analogues, and novel CPEs such as lipid synthesis inhibitors (LSIs), cell-penetrating peptides (CPPs), and ionic liquids (ILs). In addition, different types of microneedles, including 3D-printed microneedles, have been focused on in this review.

Advances in microneedles for delivery of active ingredients of natural herbals

The active ingredients of natural herbs have been extracted to act on different targets in the body to exert multiple effects. However, traditional oral administration and intravenous injection of herbal medicines are also susceptible to many side effects. Transdermal drug delivery by microneedles can overcome the shortcomings of these traditional drug delivery systems. The active ingredients of natural herbs can be delivered to the dermis or the connective tissue layer by five types of microneedles: solid, hollow, coated, dissolving, and hydrogel. Subsequently, the herbal ingredients are delivered to different target points of the body through body circulation to exert their effects. In this study, we classified the microneedles that can deliver the active ingredients of natural herbs and summarized their advantages and disadvantages as well as their preparation methods and applications, to guide the development and clinical applications of other herbal transdermal microneedles.

Finite element analysis and optimization of microneedle arrays for transdermal vaccine delivery: comparison of coated and dissolving microneedles

Microneedle arrays have recently been proposed as an alternative device for delivering vaccines into the skin. In recent years, many types of microneedles, such as coated and dissolving microneedles, have been developed with a variety of array configurations. However, the study that alongside compares the vaccine delivery efficiency of different types of microneedles and optimizes their arrangements on an array has been lacking. This study aimed to evaluate the vaccine delivery efficiency of coated and dissolving microneedles as well as to optimize the microneedle arrangements by using a three-dimensional finite element modeling approach. The constructed models describe the antigen release via diffusion, the antigen-receptor binding, and the antigen internalization by antigen-presenting cells (APCs) in the skin layers. Our modeling result reveals that the coated microneedle provides higher efficiency in activating APCs than the dissolving microneedle. It also predicts that the square arrangement of microneedles is not the optimal arrangement. According to the magnitude of APC activation, the acute-angle arrangement of microneedles outperforms the square arrangement by activating more APCs in the dermis.

Dissolving microneedles: Applications and growing therapeutic potential.

Microneedles are a rapidly developing method for the transdermal delivery of therapeutic compounds. All types of microneedles, whether solid, hollow, coated, or dissolving function by penetrating the stratum corneum layer of the skin producing a microchannel through which therapeutic agents may be delivered. To date, coated and hollow microneedles have been the most successful, despite suffering from issues such as poor drug loading capabilities and blocked pores. Dissolving microneedles, on the other hand, have superior drug loading as well as other positive attributes that make it an ideal delivery system, including simple methods of fabrication and disposal, and abundantly available materials. Indeed, dissolvable microneedles can even be fabricated entirely from the therapeutic agent itself thus eliminating the requirement for additional excipients. This focused review presents the recent developments and trends of dissolving microneedles as well as potential future directions. The advantages, and disadvantages of dissolving microneedles as well as fabrication materials and methods are discussed. The potential applications of dissolving microneedles as a drug delivery system in different therapeutic areas in both research literature and clinical trials is highlighted. Applications including the delivery of cosmetics, vaccine delivery, diagnosis and monitoring, cancer, pain and inflammation, diabetes, hair and scalp disorders and inflammatory skin diseases are presented. The current trends observed in the microneedle landscape with particular emphasis on contemporary clinical trials and commercial successes as well as barriers impeding microneedle development and commercialisation are also discussed.

Microneedles as A Magical Technology to facilitate Transdermal Drug Delivery: A Review Article

Skin drug administration is the method used to provide drugs for local or systemic therapy, which is recognized for clinical usage. It is the third-largest method of medication delivery, after only intravenous administration and oral administration. Using a transdermal delivery method makes the administration easy, and blood concentration and adverse effects can be reduced. A microneedle is a micron-sized needle with a short height of no more than 500 micrometers and a width of no more than 50 micrometers. The needle comes into contact with the epidermal layer of the skin before it gets to the dermal layer, where there is no discomfort. Several materials, such as metals, inorganic, and polymer materials, are used to create microneedles. All different types of microneedles are employed in different scientific disciplines. In recent years, microneedles have been utilized as a drug delivery method to carry pharmaceuticals, genetic codes, proteins, and vaccinations. In chemotherapy, diagnostics, treatment, and immunotherapy, microneedles were utilized.

An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses

Many types of microneedle (MN) arrays have been tested for delivery of vaccines to the skin. However, the effect of MN geometry/array design on antibody production is still unclear. Reports suggest that systemic immune responses may be affected by how MN arrays “mechanically” deliver vaccines, which can induce cell damage and act as an adjuvant. This includes parameters such as MN length/insertion depth, delivery energy/velocity, MN shape, and density. However, these effects have not been systematically investigated. Herein, the effect of MN density on antibody responses to influenza vaccination is assessed, keeping all other variables constant. MN arrays are manufactured within the “high‐density range” from 5 k microneedles cm−2 (n cm−2) to the “ultrahigh” 30 k n cm−2. Prior to this study, the highest MN density used for vaccination is 20 k n cm−2. Thus, MN array vaccination is evaluated over an unprecedented range. Cell viability is assessed in the skin after application and antibody responses at days 21/63. It is demonstrated that increasing MN density from 5 to 30 k n cm−2 increases both epidermal cell death and anti‐influenza IgG1, without an increase in anti‐influenza IgG2a. This suggests that MN density has a direct adjuvant effect on immune responses through Th2‐mediated signalling—a response critical for human vaccination.

Microneedles (MNs) - A versatile transdermal drug delivery system: Types, Fabrication Methodology, Release Mechanism, Evaluation Parameters, Biological Application and Clinical Case Studies

Because of the limitations of the oral drug delivery system, as well as the discomfort associated with the usage of needles in the case of injections, drug delivery research has shifted significantly toward the transdermal route of administration. Topical creams, gels, and transdermal patches are the most often utilised means of transdermal administration of drugs. Since the stratum corneum layer of the skin acts as a barrier to a drug molecule, the effect of the majority of therapeutic agents is limited. As a result, only a small number of molecules are able to reach the site of action. A new type of delivery method, known as microneedles, is being developed to improve the distribution of drugs through this route while also overcoming the various issues associated with existing formulations. Non-invasive and painless feature of microneedles have making them ideal for self-administration. This review describes various type of microneedles and their design, fabrication methodology, various materials used in fabrication of microneedles, drug release mechanism from the microneedles, evaluation parameters, it’s biological application, update about recent clinical studies and in last, challenges and future perspective of microneedles as drug delivery system.