Microneedles For Drug Delivery Research Articles

Visualization of the degradation of long-acting microneedles and correlation of drug release in vivo based on FRET mechanism

This study introduces a live imaging technique for real-time, non-invasive monitoring of drug release from long-acting microneedles using FRET (Fluorescence Resonance Energy Transfer). Employing Cy5.5 and Cy7 as FRET pairs and levonorgestrel as the model drug, we fabricated microneedles with varying PLGA molecular weights, demonstrating distinct release profiles. The FRET-PLGA-10-MN demonstrated a rapid drug release profile, reaching nearly complete release within a two-day period, while FRET-PLGA-30-MN showed a sustained release over four days. Sensitized Emission FRET (SE-FRET) optimized the imaging process, providing a robust correlation between FRET signals and drug absorption. This method surpasses traditional pharmacokinetic studies by offering a more efficient and comprehensive analysis of microneedle release dynamics in vivo, paving the way for enhanced long-acting microneedle design and therapeutic outcomes. Statement of significance1. FRET technology was applied to microneedle drug delivery system for the first time, which realized real-time, quantitative and non-invasive monitoring of drug release process.2. The long-term microneedle technique was combined with sensitized emission method, and the FRET remaining ratio was innovatively used to investigate the FRET characteristics of microneedles, and the fluorescence ratio of FRET and donor double-channel was quantitatively calculated.3. The correlation between visual fluorescence images of FRET effect and semi-quantitative calculation results based on fluorescence intensity and drug release in vivo with drug-loaded microneedles was analyzed.

A Review: Microneedle Drug Delivery

The various common techniques for transdermal medication delivery include hypodermic needles, topical lotions, and transdermal patches. Because the stratum corneum layer of the skin acts as a barrier for molecules, the action of most therapeutic medicines is restricted, and only a few molecules are able to penetrate and reach the location of action. A novel type of delivery technology known as micro needles aids in improving medication distribution through this channel and addressing the many issues associated with traditional formulations. Because of the problems associated with oral medication delivery methods, transdermal drug administration utilising micro needles is gaining popularity. The possibilities and uses of micro needles are discussed in this review. Micro needles of many sorts can be manufactured, including solid, dissolving, hydrogel, coated, and hollow micro needles. The fabrication process chosen is determined on the kind and material of the micro needle. This technique is now being used in a variety of sectors, including oligonucleotide distribution, vaccine administration, insulin delivery, and even cosmetics.

Polymeric Microneedle Drug Delivery Systems: Mechanisms of Treatment, Material Properties, and Clinical Applications-A Comprehensive Review.

Our comprehensive review plunges into the cutting-edge advancements of polymeric microneedle drug delivery systems, underscoring their transformative potential in the realm of transdermal drug administration. Our scrutiny centers on the substrate materials pivotal for microneedle construction and the core properties that dictate their efficacy. We delve into the distinctive interplay between microneedles and dermal layers, underscoring the mechanisms by which this synergy enhances drug absorption and precision targeting. Moreover, we examine the acupoint-target organ-ganglion nexus, an innovative strategy that steers drug concentration to specific targets, offering a paradigm for precision medicine. A thorough analysis of the clinical applications of polymeric microneedle systems is presented, highlighting their adaptability and impact across a spectrum of therapeutic domains. This review also accentuates the systems' promise to bolster patient compliance, attributed to their minimally invasive and painless mode of drug delivery. We present forward-looking strategies aimed at optimizing stimulation sites to amplify therapeutic benefits. The anticipation is set for the introduction of superior biocompatible materials with advanced mechanical properties, customizing microneedles to cater to specialized clinical demands. In parallel, we deliberate on safety strategies aimed at boosting drug loading capacities and solidifying the efficacy of microneedle-based therapeutics. In summation, this review accentuates the pivotal role of polymeric microneedle technology in contemporary healthcare, charting a course for future investigative endeavors and developmental strides within this burgeoning field.

Plant-Derived Chinese Herbal Hydrogel Microneedle Patches for Wound Healing.

Several natural Chinese herbal medicines have demonstrated considerable potential in facilitating wound healing, while the primary concern remains centered around optimizing formulation and structure to maximize their efficacy. To address this, a natural microneedles drug delivery system is proposed that harnesses gelatinized starch and key Chinese herbal ingredients-aloe vera and berberine. After gelatinized and aged in a well-designed mold, the starch-based microneedles are fabricated with suitable mechanical strength to load components. The resulting Chinese herbal hydrogel microneedles, enriched with integrated berberine and aloe, exhibit antibacterial, anti-inflammatory, and fibroblast growth-promoting properties, thereby facilitating wound healing in the whole process. In vivo experimental results underscore the notable achievements of the microneedles in early-stage antibacterial effects and subsequent tissue reconstruction, contributing significantly to the overall wound healing process. These results emphasize the advantageous combination of traditional Chinese medicine with microneedles, presenting a novel strategy for wound repair and opening new avenues for the application of traditional Chinese medicine.

Magnetically triggered ingestible capsule for localized microneedle drug delivery

Magnetically triggered ingestible capsule for localized microneedle drug delivery

Magnetic-navigable silk fibroin microneedles for oral drug delivery: Ensuring long-lasting helicobacter pylori eradication and rapid hemostasis in the stomach

The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNsD) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.

Progress on microneedle drug delivery systems for the treatment of corneal diseases

Corneal diseases are prevalent eye conditions in China, and the lack of effective treatment in the short term can lead to blindness. However, delivering drugs to the cornea safely and effectively poses a significant challenge due to the presence of ocular barriers and clearance mechanisms. Conventional drug delivery methods exhibit low bioavailability, making it difficult to achieve therapeutic effects. Microneedles, with their ability to penetrate ocular surface barriers effectively, offer a low-invasive and highly promising drug delivery technology. This article introduces the main delivery barriers on the ocular surface, classifies microneedles, and highlights the latest developments in the treatment of corneal diseases. Finally, the potential challenges of applying microneedle delivery systems to the ocular surface are analyzed, aiming to provide insights for the clinical application of microneedles in corneal diseases.

Microneedle Patch Delivery of PLCG1-siRNA Efficient Enhanced Temozolomide Therapy for Glioblastoma.

The blood-brain barrier (BBB) and drug resistance present challenges for chemotherapy of glioblastoma (GBM). A microneedle (MN) patch with excellent biocompatibility and biodegradability was designed to bypass the BBB and release temozolomide (TMZ) and PLCG1-siRNA directly into the tumor site for synergistic treatment of GBM. The codelivery of TMZ and PLCG1-siRNA enhanced DNA damage and apoptosis. The potential mechanism behind this enhancement is to knockdown of PLCG1 expression, which positively regulates the expression of signal transducer and activator of transcription 3 genes, thereby preventing DNA repair and enhancing the sensitivity of GBM to TMZ. The MN patch enables long-term sustainable drug release through in situ implantation and increases local drug concentrations in diseased areas, significantly extending mouse survival time compared to other drug treatment groups. MN drug delivery provides a platform for the combination treatment of GBM and other central nervous system diseases.

Programmed Release METTL3-14 Inhibitor Microneedle Protects Myocardial Function by Reducing Drp1 m6A Modification-Mediated Mitochondrial Fission.

M6A modification is an RNA-important processing event mediated by methyltransferases METTL3 and METTL14 and the demethylases. M6A dynamic changes after myocardial infarction (MI), involved in the massive loss of cardiomyocytes due to hypoxia, as well as the recruitment and activation of myofibroblasts. Balanced mitochondrial fusion and fission are essential to maintain intracardiac homeostasis and reduce poststress myocardial remodeling. Double-layer programmed drug release microneedle (DPDMN) breaks the limitations of existing therapeutic interventions in one period or one type of cells, and multitargeted cellular combination has more potential in MI therapy. By employing hypoxia-ischemic and TGF-β1-induced fibrosis cell models, we found that METTL3-14 inhibition effectively decreased cardiomyocyte death through the reduction of mitochondrial fragmentation and inhibiting myofibrillar transformation. DPDMN treatment of MI in rat models showed improved cardiac function and decreased infarct size and fibrosis level, demonstrating its superior effectiveness. The DPDMN delivers METTL3 inhibitor swiftly in the early phase to rescue dying cardiomyocytes and slowly in the late phase to achieve long-term suppression of fibroblast over proliferation, collagen synthesis, and deposition. RIP assay and mechanistic investigation confirmed that METTL3 inhibition reduced the translation efficiency of Drp1 mRNA by 5'UTR m6A modification, thus decreasing the Drp1 protein level and mitochondrial fragment after hypoxic-ischemic injury. This project investigated the efficacy of DPDMNs-loaded METTL3 inhibitor in MI treatment and the downstream signaling pathway proteins, providing an experimental foundation for the translation of the utility, safety, and versatility of microneedle drug delivery for MI into clinical applications.

The Microneedle Drug Delivery System and some Recent Obstacles in its Implementation

Abstract: Transdermal Drug Delivery (TDD) is a non-painful way of systemically delivering medications by applying a drug formulation to intact, healthy skin. The drug particles’ limitations, including the molecular weight and hydrophilicity, preclude TDD from being exploited extensively. Microneedle arrays (MNA) are an efficient way for medication delivery via the skin. Microneedles enhance medication administration. Microneedles are either long, hollow, or coated. They are designed to target the skin as quickly and safely as possible, without the use of chemical, nanoparticle, or hypodermic injections and without requiring micro-pen or physical strategies. Solid microneedles include micropores, whereas hollow microneedles provide a more profound passage into the dermis. Investigations have been conducted on the use of dissolving microneedles for the delivery of vaccines, while coated microneedles have been utilized to efficiently deliver vaccines. This paper attempts to provide a comprehensive summary of the current state of MNA science, with a focus on methodologies, issues, implementations, and the types of materials lately dispersed by such devices. In addition, some information regarding the components and manufacturing methods is provided. Metals, silicone, ceramics, synthetic materials, and biodegradable polymers, such as carbohydrates, can be utilized to manufacture microneedles.

Construction and application of microneedle-mediated photothermal therapy and immunotherapy combined anti-tumor drug delivery system

Conventional treatments for tumors were frequently accompanied by drawbacks and side effects. It might be useful to use the revolutionary microneedle technology which combines photothermal therapy with tumor immunotherapy. In this study, we created a microneedle drug delivery system with mercapto-modified gold nanorods and immune checkpoint blocker anti-PD-1 polypeptide. With good mechanical strength, the microneedle system can efficiently penetrate the skin and deliver drugs. When inserted into human skin, anti-PD-1 peptides and gold nanorods can be released, boosting the capacity of cytotoxic T lymphocytes to destroy tumor cells. Additionally, the elimination of the tumor is aided by the production of heat while being exposed to near-infrared light. This microneedle drug delivery system can enhance the immunological reaction and prolong the survival time of mice. Moreover, it has been demonstrated that the system has mild toxic and side effects on normal tissues and can effectively inhibit the growth of tumors, indicating a bright prospect for the treatment of cancers.

A review Recent Advanced of Fabrication Techniques and Application of Micro-Needle

Micro-needles are micron-scaled medical devices used to administer vaccines, drugs, and other therapeutic agents. Micro-needles typically measure 0.1–1 mm in length. A variety of materials such as silicon, ceramic, stainless steel and polymers have been used for fabrication. Micro-needles devices are compatible with the delivery of both Small and macromolecular therapeutics. Micro-needles (MNs) are currently being utilized to enhance transdermal delivery of small and large molecules. With the emergence of micro fabrication manufacturing technology over the past several decades, (MNs) have been developed by academic laboratories and pharmaceutical companies. Micro-needle has useful in application in diseases such as type 2 Diabetes, cancer treatment, Glaucoma, and also useful application in cosmetic, vaccine therapy. The present article provides an overview of micro-needle, fabrication technique, general properties, Material and methods of fabrication techniques, application and advantages and disadvantages of micro-needle drug delivery system. Micro-needles (MNs) are currently being utilized to enhance trans-dermal delivery of small and large molecules. With the emergence of micro fabrication manufacturing technology over the past several decades, have been developed by academic laboratories and pharmaceutical companies.

Novel synergistic approaches of protein delivery through physical enhancement for transdermal microneedle drug delivery: A review

Novel synergistic approaches of protein delivery through physical enhancement for transdermal microneedle drug delivery: A review

Three Dimensional Printing and Its Applications Focusing on Microneedles for Drug Delivery.

Microneedles (MNs) are considered to be a novel smart injection system that causes significantly low skin invasion upon puncturing, due to the micron-sized dimensions that pierce into the skin painlessly. This allows transdermal delivery of numerous therapeutic molecules, such as insulin and vaccines. The fabrication of MNs is carried out through conventional old methods such as molding, as well as through newer and more sophisticated technologies, such as three-dimensional (3D) printing, which is considered to be a superior, more accurate, and more time- and production-efficient method than conventional methods. Three-dimensional printing is becoming an innovative method that is used in education through building intricate models, as well as being employed in the synthesis of fabrics, medical devices, medical implants, and orthoses/prostheses. Moreover, it has revolutionary applications in the pharmaceutical, cosmeceutical, and medical fields. Having the capacity to design patient-tailored devices according to their dimensions, along with specified dosage forms, has allowed 3D printing to stand out in the medical field. The different techniques of 3D printing allow for the production of many types of needles with different materials, such as hollow MNs and solid MNs. This review covers the benefits and drawbacks of 3D printing, methods used in 3D printing, types of 3D-printed MNs, characterization of 3D-printed MNs, general applications of 3D printing, and transdermal delivery using 3D-printed MNs.

3D-printed morphology-customized microneedles: Understanding the correlation between their morphologies and the received qualities

Despite remarkable progress in the last decade in transdermal microneedle drug delivery systems, great difficulties in precisely manufacturing microneedles with sophisticated microstructures still strongly retard their practical applications. Herein we propose morphology-customized microneedles (spiral, conical, cylindroid, ring-like, arrow-like and tree-like) fabricated by stereolithography (SLA) based 3D-printing technique, and in-depth investigate the correlation between the customized morphologies and the received qualities of the corresponding microneedles such as the mechanical properties and skin penetration behavior, drug loading capacity and the drug release profiles. Results indicated that 3D-printed morphology-customized microneedles not only enhanced the mechanical strength but also improved both drug loading capacity and drug release behavior, which resulted from their highly controllable and 3D-printable morphologies (surface area and volume). And the in vivo study demonstrated that the 3D-printed morphology-customized microneedles successfully promoted the transdermal delivery of the loaded drug (verapamil hydrochloride) with an enhanced therapeutic efficacy for the treatment of hypertrophic scar.

MICRONEEDLES A POSSIBLE SUCCESSOR TECHNOLOGY FOR TDDS: A PATENT ANALYSIS

The market size for transdermal drug delivery systems was assessed at USD 5.9 billion in 2020 and is expected to reach USD 8.4 billion by 2028, expanding at a compound annual growth rate (CAGR) of 4.5% from 2021 to 2028. Micro Jet injectors, iontophoresis, electroporation, sonophoresis, microneedles, powdered injection, surface ablation, jet injectors and stripping by tape are some of the methods that enhance the delivery and ease of administration of larger molecules which is the major hindrance in case of Transdermal drug delivery system (TDDS). This type of delivery offers immediate delivery and avoids lag time. Microneedles are hollow cannulas inserted into the skin at 50 µm to 500 µm. The microneedle drug delivery systems market is projected to register a CAGR of 7.8% during the forecast period of 2022-2027. The microneedle drug delivery systems market is segmented by product type (solid, hollow, coated, and dissolvable), application (drug delivery, vaccine delivery, dermatology, and other applications), and geography (North America, Europe, Asia-Pacific, Middle-East and Africa, and South America). This review summerizes the recent patents granted in the area of micro-needling in the year 2022 and also the commercial market of microneedles until now.

Microneedles : A Smart Approach for Transdermal Drug Delivery System

Due to the limitations of oral and parenteral medication delivery, which result in patient noncompliance, the Novel Drug Delivery System is currently more effective than the Conventional Drug Delivery System. The transdermal drug administration method is frequently used to deliver medications through the skin for both local and systemic effects. The stratum corneum's epidermal layer serves as a significant barrier for the transport of drugs via the skin. We can release a medicine by various techniques in a regulated manner with the aid of different sorts of microneedle patches on the skin, depending on the microneedle's design. Microneedles are made from a range of materials, including silicon, stainless steel, polymers, metals, and carbohydrates. These materials have been utilised to create coated, solid, dissolving, hollow, and hydrogel-forming microneedles. These microneedles transport different medications, proteins, vaccines, and immunobiological substances, and they are crucial in the treatment of many illnesses like cancer, diabetes, and pain management. The development of the microneedle faces numerous problems, including those related to stability, dosage accuracy, skin irritation cost, and more. The types, fabrication materials and processes, and applications of the microneedle drug delivery system are discussed in this review.

The Application of Nanotechnology in Microneedles for Drug Delivery

The Application of Nanotechnology in Microneedles for Drug Delivery

Advancement in microneedles as minimally invasive delivery system for pharmaceutical and biomedical application: A review

Microneedle expands as therapeutics and diagnostics thereby dramatically affecting the delivery system in health care. MN arrays are made of several micron-sized needles with a height usually between 25 and 2000 µm, of various forms and compositions such as silicon, metal, and biodegradable polymers. With the help of current developments in additive manufacturing procedures, such as two-photon polymerization fabrication and 3D printing, microneedle designs with feature sizes ranging from sub-micron to millimeters may be produced. The technology has the potential to provide feasible methods to deliver medications via impermeable barriers in addition to being minimally invasive and patient-compliant and having the capacity to cross many biological barriers. The method has been effective in removing the barriers to direct drug delivery to the targeted areas, increasing the efficiency and lowering the dose needed. A considerable quantity of MN-mediated vaccine candidates have reportedly demonstrated promising outcomes in preclinical and clinical studies. Vaccine delivery is used as an advanced technique. They are a better option since they may be self-administered, painless, and provide improved immunogenicity. In addition to providing an overview of microneedle drug delivery system, selection of materials, designs, manufacturing techniques, and possible safety implications, and applications, the current paper also sheds light on probable future developments in the area of microneedle innovation.

Recent Development of Drug Delivery Systems through Microfluidics: From Synthesis to Evaluation.

Conventional drug administration usually faces the problems of degradation and rapid excretion when crossing many biological barriers, leading to only a small amount of drugs arriving at pathological sites. Therapeutic drugs delivered by drug delivery systems to the target sites in a controlled manner greatly enhance drug efficacy, bioavailability, and pharmacokinetics with minimal side effects. Due to the distinct advantages of microfluidic techniques, microfluidic setups provide a powerful tool for controlled synthesis of drug delivery systems, precisely controlled drug release, and real-time observation of drug delivery to the desired location at the desired rate. In this review, we present an overview of recent advances in the preparation of nano drug delivery systems and carrier-free drug delivery microfluidic systems, as well as the construction of in vitro models on-a-chip for drug efficiency evaluation of drug delivery systems. We firstly introduce the synthesis of nano drug delivery systems, including liposomes, polymers, and inorganic compounds, followed by detailed descriptions of the carrier-free drug delivery system, including micro-reservoir and microneedle drug delivery systems. Finally, we discuss in vitro models developed on microfluidic devices for the evaluation of drug delivery systems, such as the blood–brain barrier model, vascular model, small intestine model, and so on. The opportunities and challenges of the applications of microfluidic platforms in drug delivery systems, as well as their clinical applications, are also discussed.