Transforming Biologics Delivery through Microneedles

Recent advances in microneedle designs and their applications in drug and cosmeceutical delivery

Tiny titans- unravelling the potential of polysaccharides and proteins based dissolving microneedles in drug delivery and theranostics: A comprehensive review

Transdermal drug delivery is a viable and clinically proven route of administration. This route specifically requires overcoming the mechanical barrier provided by the Stratum Corneum of epidermis and vascular and nervous networks within the dermis. First-generation Transdermal patches and second-generation iontophoretic patches have been translated into commercial clinical products successfully. The current review reports different studies that aim to enhance the transdermal delivery of biopharmaceutical using microneedles and their effect on drug delivery. Microneedles (MN) are the micron-scale hybrid between transdermal patches and hypodermic syringes. Microneedles are tested and proven to show better delivery of the drugs, overcoming the drawbacks of hypodermic syringes. Multiple microneedles designs have been fabricated i.e. solid, coated, hollow, and polymer microneedles. Hollow microneedles are shorter in length but similar to hypodermic needles and have pore for infusion of liquid formulation of the drug. Solid microneedles a patch is applied after creating a hole in the skin; Drugs are coated on the surface of Coated microneedles; Polymer microneedles can be of different types like dissolving, non-dissolving or hydrogel-forming made up of polymers. Various advantages and limitations associated with the use of these techniques are discussed. Delivery of peptide and protein molecules with microneedles represents a significant opportunity for a better clinical outcome and hence value creation compared to standard injectable routes of administration. The advancement in various formulation and microfabrication techniques are currently being focused to aid the delivery of protein drugs via microneedles. The most recent advances and limitations in Microneedles -mediated protein and peptide delivery were discussed.

In recent years, microneedle (MN) patches have emerged as an alternative technology for transdermal delivery of various drugs, therapeutics proteins, and vaccines. Therefore, there is an urgent need to understand the status of MN-based therapeutics. The article aims to illustrate the current status of microneedle array technology for therapeutic delivery through a comprehensive review. However, the PubMed search was performed to understand the MN's therapeutics delivery status. At the same time, the search shows the number no of publications on MN is increasing (63). The search was performed with the keywords "Coated microneedle," "Hollow microneedle," "Dissolvable microneedle," and "Hydrogel microneedle," which also shows increasing trend. Similarly, the article highlighted the application of different microneedle arrays for treating different diseases. The article also illustrated the current status of different phases of MN-based therapeutics clinical trials. It discusses the delivery of different therapeutic molecules, such as drug molecule delivery, using microneedle array technology. The approach mainly discusses the delivery of different therapeutic molecules. The leading pharmaceutical companies that produce the microneedle array for therapeutic purposes have also been discussed. Finally, we discussed the limitations and future prospects of this technology.

Metal-organic frameworks (MOFs) are porous materials renowned for their high porosity, large specific surface area, biocompatibility, and biodegradability. Hydrogel microneedles (MNs) is an emerging technology that minimally disrupts the skin or mucosal membranes, bypassing gastrointestinal absorption and the rapid metabolism typical of oral drug delivery. Over the past few decades, both MOFs and MNs have found applications across a range of fields. However, MOFs alone cannot penetrate the skin or mucosal barrier to deliver drugs effectively, and MNs have limited direct loading capacity. When combined, MOFs enhance the loading efficiency of therapeutic agents in hydrogel MNs and optimize their release kinetics. Additionally, the incorporation of MOFs improves the mechanical properties of hydrogel MNs, increasing their permeability to the skin. In turn, hydrogel MNs enable MOFs-whether therapeutically active or drug-loaded-to bypass the skin or mucosal barrier and deliver active compounds directly to the target site for localized treatment. This review discusses the structural features and preparation methods of MOFs and MOF-based MNs, explores their synergistic potential, and highlights strategies for integrating MOFs with MNs to enhance transdermal drug delivery in applications such as wound healing, scar management, acne treatment, and tumor suppression. Finally, we examine the challenges and future potential of MOF-based MNs and offer insights into their role in advancing transdermal therapies.

BackgroundDespite its popularity, acceptability, and convenience, the oral route is not the classical route for the administration of all critical bioactives including lipophilic drugs, proteins, and peptides. Recent advances in drug delivery have identified the transdermal route as a compelling alternative channel for improved delivery of essential biomolecules due to the illuminating advantages derived from this route. In order to circumvent the poor permeation of the stratum corneum by transdermal patches, microneedles (MNs) technology, which combine the advantages of parenteral delivery using hypodermic needles and transdermal delivery, has been unveiled as a novel biomimetic technology for efficient and effective transport of payloads across the stratum corneum.Main body of abstractThe concept of MNs was first documented by Chambers in 1921 when he reported some problems encountered during experimentation using Echinoderm eggs. Since the first patent recorded in 1976, there has been consistent interest and funding in development of MNs for various biomedical applications. MNs have been developed and classified based on their physical attributes and functional profiles into solid, coated, hollow, dissolvable, and swellable or hydrogel-based MNs. These devices are fabricated using advanced techniques like 3D bioprinting, laser methods, photolithography, and molding, and applying materials such as carbohydrates, silica, ceramics, metals, glass and polymers. MNs could be characterized based on their morphological, geometrical, surface, mechanical properties, biocompatibility, and permeability profiles. Evidences have shown that MNs could be commercialized for various clinical adaptations. The numerous biomedical applications of microneedles in drug, peptide, and protein delivery attest to the versatility and dynamic nature of the fabrication techniques, and the pliability of the formulation materials. In spite of the enormous potentials of MNs, extant literature has shown that MNs also have their own share of limitations like every novel technology designed for theranostic purposes.Short conclusionIn this review, we have escalated discussions on the progress and advances made in the development and use of MNs by summarizing the benefits, limitations, fabrication techniques, fabrication materials, characterization methods, therapeutic applications, sterilization and stability considerations, safety and toxicological concerns, regulatory guidelines, and tips for successful commercialization of MNs.

According to World Health Organization (WHO) estimates, around 900 million people globally are affected by various skin diseases, which cause significant physical and psychological distress and place a heavy economic burden on healthcare systems. The primary challenges in treating skin diseases include the limited transdermal drug absorption due to the skin barrier, the side effects associated with medications, and the recurring nature of these conditions that lead to prolonged patient suffering. Microneedles (MNs) have emerged as a promising transdermal drug delivery technology, able to painlessly penetrate the stratum corneum and deliver medications directly to the affected area. Various types of MNs technology have been developed, including dissolvable MNs (DMNs), solid MNs, coated MNs, hollow MNs, and hydrogel-based MNs. DMNs, especially, offer non-invasive drug delivery with sustained release through their dissolvable nature. Combining active ingredients from Chinese Herbal Medicine (CHM), known for their natural anti-inflammatory and antibacterial properties with minimal side effects, with DMNs provides an effective approach for treating skin diseases. This review aims to provide a comprehensive overview of the application of CHM-based DMNs in treating psoriasis, acne, hypertrophic scars, keloids, melanoma, atopic dermatitis, and other skin conditions. Additionally, it will introduce the manufacturing methods for CHM-based DMNs, explore strategies for integrating CHM with MNs, and summarize the broad translational potential and challenges of this technology in the field of dermatology.

6 - Microneedles for drug delivery and monitoring

Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety.

Microneedle (MN) delivery system has been greatly developed to deliver drugs intothe skin painlessly, noninvasively, and safety. In the past several decades,various types of MNs have been developed by the newer producing techniques.Briefly, as for the morphologically, MNs can be classified into solid, coated,dissolved, and hollow MN, based on the transdermal drug delivery methods of“poke and patch,” “coat and poke,” “poke and release,” and “poke and flow,”respectively. Microneedles also have other characteristics based on thematerials and structures. In addition, various manufacturing techniques havebeen well-developed based on the materials. In this review, the materials,structures, morphologies, and fabricating methods of MNs are summarized. Aseparate part of the review is used to illustrate the application of MNs todeliver vaccine, insulin, lidocaine, aspirin, and other drugs. Finally, thereview ends up with a perspective on the challenges in research and developmentof MNs, envisioning the future development of MNs as the next generation of drugdelivery system.

Dissolving polymeric microneedle arrays for electrically assisted transdermal drug delivery

Development of hyaluronic acid-silica composites via in situ precipitation for improved penetration efficiency in fast-dissolving microneedle systems

Rapidly separating microneedles for transdermal drug delivery

Hollow microneedle (MN) arrays offer versatility and control to transdermal drug delivery systems where a variety of drugs and their continuous supply are concerned. They may be used as a standalone device or be integrated with the drug reservoir or micropump. An important aspect in this regard is the effective fluidic communication between the reservoir and the MNs on a robust substrate. In a novel attempt of its kind, we present the development hollow SU-8 MNs on a pre-etched silicon wafer having through holes. SU-8 MNs are fabricated by direct laser writing by aligning them on the silicon substrate with microfluidic ports pre-etched by wet chemical etching. Each process step was optimized after a parametric study. The optimized MNs (500–600 µm length, 100 µm outer diameter and 40 µm inner diameter) have an aspect ratio of 5. The MNs have been characterized for mechanical strength and biological insertion tests for their effectiveness in puncturing the skin without breaking. The maximum compressive force and bending forces for the MNs are 0.27 N and 0.022 N per needle, which are higher than the resistive skin penetrating forces. The microfluidic characterizations show the development of hollow MN lumen with a flowrate of around 0.93 µl s−1 at 2 KPa pressure difference at the inlet. The array of 10 × 10 MNs with 500 µm spacing was able to successfully penetrate mice and rat skin without any breakage.

Advances in Drug Delivery and Theranostics