Microneedle patch casting with a microstructured carbon master for improved drug delivery

Transdermal drugs are drugs that are administered through the skin. This type of drug administration allows the controlled release of the drug over a longer period of time¹. Transdermal drug patches are commonly used to treat conditions such as chronic pain, osteoarthritis, nicotine addiction, and hormone replacement therapy. The medication is usually stored in a reservoir within the patch and released through the skin using a combination of diffusion and iontophoresis, which applies a small electrical current to enhance the transport of the medication through the skin. Transdermal drug patches can deliver a consistent dose of medication, which may improve effectiveness and reduce the risk of side effects compared to oral or injectable forms of the same medication.^2.3.

Microneedles (MNs) are miniaturized medical devices that contain a series of micronized needles. They are small, typically less than 1 mm long, and are used for transdermal drug delivery. They are designed to penetrate the upper layers of the skin (stratum corneum) without reaching nerve endings and blood vessels, reducing the pain and bleeding associated with traditional injection needles.^4.5. It is a minimally invasive drug delivery system that can administer drugs painlessly and collect samples for examination. They are mild and less harmful to the human body and easy to use for medical staff and patients.⁵. MNs can be made from various materials such as metal, silicon and biodegradable polymers. They can be arranged in various configurations including arrays, patches and solid structures⁶.

MNs can improve drug transport through the skin by creating small channels through the stratum corneum, allowing increased drug diffusion⁷They have many advantages over conventional injection needles, such as ease of use, painlessness, minimal invasiveness and greater patient acceptance.^8.9. They also have the potential to reduce needlestick injuries and cross-contamination, making them safer for both patients and healthcare workers. MNs have the potential for use in various applications, including real-time biomarker detection¹⁰. They can be used to efficiently deliver drugs, vaccines, insulin for diabetes, cancer therapeutics, proteins, small molecules, liquid drugs and other biomolecules to different parts of the human body to treat diseases.^11,12. They can also be used in paper chips, microfluidic systems and other sensitive detection techniques^13,14. In addition, they can transport cells and facilitate cell culture, cytological testing, cytokine delivery, and more.^15,16They are also being researched for use in cosmetics and skin care products, as well as in gene therapy and for painless blood collection.^17,18,19,20There is a growing interest in developing new generation “smart MNs” that are bionic, bio-derived or biocompatible and have unique properties such as skin adhesion, solubility, responsiveness and tip-substrate releasability to meet the needs of different application scenarios such as wearable devices, rapid delivery, responsive delivery or detection and sustained delivery²¹.

From the perspective of transdermal drug delivery, porous materials play a crucial role in developing effective and efficient transdermal patches. These materials are used in transdermal patches to improve the penetration of the drug through the skin. The pores in these materials act as channels through which the drug passes through the skin into the bloodstream. In addition, porous materials increase the surface area of ​​the patch, which allows a larger amount of drug to be delivered.²². One of the biggest challenges in developing transdermal patches is controlling drug release. Porous materials overcome this challenge by regulating the size and shape of the pores as well as the surface area of ​​the patch. This control can be achieved by using different types of polymers, such as hydrogels, which allow for controlled release of drugs over a period of time.²³.

Previously, our research team developed a smart MN by using a simple approach of coating a porous polymer layer on stainless steel MNs (SS-MNs) and applied it to glucose-dependent insulin delivery and smart drug delivery for wound healing.^24,25,26. SS-MNs have the advantages of being biocompatible, easy to fabricate, and most importantly, they have high mechanical strength. However, when using stainless steel as the material for MNs, the poke-and-pull method is inconvenient, and the sharp tip remains after use, which generates medical waste. Most importantly, it is difficult to load drugs directly onto SS-MNs. Therefore, our research team proposed a porous surface coating method as a means of loading drugs onto SS-MNs.⁹. However, this method has the disadvantage that it cannot accommodate large amounts of drugs. To overcome this limitation, MNs have been fabricated from polymers instead of metals, which dissolve in the body, avoiding the generation of medical waste and relatively increasing the drug loading. In addition, an approach that allows the administration of multiple drugs is presented. The fabrication methods for polymer MNs vary depending on the polymer properties, but the most commonly used method is micromolding, which requires a mold. Mold fabrication methods include photolithography, laser processing, and 3D printing. However, photolithography requires complex processes to produce molds of different shapes and sizes. Laser processing and 3D printing have poor mold accuracy in micromolding.²⁷. In this study, micromachining was used to manufacture a MN mold. Micromachining is a relatively simple process compared to other methods and enables the cost-effective manufacture of micromolds of various shapes^28.29Fine-grained carbon with high purity was used as the mold material. Since it is a brittle material, no burrs are generated during mechanical processing, which makes it advantageous for machining micro molds.³⁰Here, the smart features implemented in the previously reported SS-MNs were applied to the new polymer MNs and fabricated using a new approach that has not been attempted before.

To achieve sufficient drug loading and analysis samples and improve drug penetration while keeping administration painless, we developed two types of MN arrays in patch form to enable active and passive stimulation of drug delivery with increased therapeutic effect. In the first array, we fabricated porous polymer coatings on the MNs and the base of the patch, which increased loading efficiency and enabled automatic “drug release” in response to the body’s pH conditions. The pores of the porous polymer layer trapped the drug and formed channels for drug flow. The MNs and base were coated with a stimulus-responsive polymer. When inserted into the body, the responsive MN coating was dissolved by the body fluid and the loaded drug was released in response to body stimulation. Upon dissolution of the protective coating on the MN periphery, the drug loaded on it dissolved in the body. In addition, the pores were interconnected, so the drug loaded on the MN-based began to flow through these pores and distributed throughout the body, showing three times higher drug release efficiency than metallic MNs.

In the second array, the MNs were connected to the drug reservoir through holes in the base of the MN array. The drug from the reservoir flowed through these holes into the porous base coating of the MN array and then through the pores of the porous coating of the MNs and diffused in the body. Combined with microfluidic chips or hydrogels, this can lead to advanced research, such as increasing drug loading and applying the release of two or more types of drugs. Thus, we achieved continuous drug flow using a simple and less expensive manufacturing method.