Microneedle for transdermal drug delivery: current trends and fabrication

Transdermal delivery has the advantage of bypassing the first-pass effect and allowing sustained release of the drug. However, the drug delivery is limited owing to the barrier created by the stratum corneum. Microneedles are a transdermal drug delivery system that is painless, less invasive, and easy to self-administer, with a high drug bioavailability.

Area covered
The dose, delivery rate, and efficacy of the drugs can be controlled by the microneedle design and drug formulations. This review introduces the types of microneedles and their design, materials used for fabrication, and manufacturing methods. Additionally, recent biological applications and clinical trials are introduced.

Expert opinion
With advancements made in formulation technologies, the drug-loading capability of microneedles can be improved. 3D printing and digital technology contribute to the improvement of microneedle fabrication technology. However, regulations regarding the manufacture of microneedle products should be established as soon as possible to promote commercialization.

Continue reading here: Jung, J.H., Jin, S.G. Microneedle for transdermal drug delivery: current trends and fabrication. J. Pharm. Investig. (2021). https://doi.org/10.1007/s40005-021-00512-4

Materials for microneedlesVarious materials, from metal to polymer, are used in microneedles, depending on the design or components of the patch. Generally, microneedle materials should have sufficient mechanical strength for skin insertion (Dharadhar et al. 2019). Non-dissolving microneedles are inert, biocompatible, and sufficiently strong for skin insertion without causing an immune response. In contrast, the matrices of the coated and dissolving microneedles should generally be water-soluble and biocompatible. In addition, it should dissolve or disintegrate in the body without inducing toxicity. Compatibility between the matrices and drugs is critical during the manufacturing process, storage, and transportation of the microneedle patches. The characteristics of various materials used in microneedles are described below.

Silicon
Silicon has sufficient mechanical strength for skin insertion; therefore, it is often used for manufacturing solid and coated microneedles (Hoang et al. 2015; McGrath et al. 2011). Silicon microneedles can be precisely manufactured with small sharp tips with lengths of 100 μm or less using deep reactive ion etching and photolithography (Donnelly et al. 2009; Henry et al. 1998; Li et al. 2019c). However, the equipment used is expensive, the process is expensive, and the production speed is slow (Banga 2009). The silicon microneedle can cause safety problems when it breaks from the skin and fragments remain in the tissue (McGrath et al. 2011). Recently, silicon is being used in reverse master molds rather than in solid microneedles (Lutton et al. 2015).

Metal
Metal materials exhibit high mechanical and tensile strength; therefore, they can easily pass through the skin. They are used to produce solid, coated, and hollow microneedles. In general, stainless steel (Gupta et al. 2011) and titanium (Ti) (Choi et al. 2013; McCarthy et al. 2011; Skoog et al. 2015) are typical metal materials used in microneedles. Stainless steel is the most used metal material for microneedle production; however, it exhibits a faster corrosion rate than Ti alloy (Amalraju et al. 2012). Ti alloys possess stronger mechanical strength than stainless steel; however, they are more expensive (Amalraju et al. 2012).

Polymer
The polymers used for microneedle manufacture should be water-soluble, biocompatible, and mechanically strong for skin insertion (Praustniz 2017). The most common method for producing polymer microneedle is the solvent casting method. This method involves obtaining an inverse mold from the microneedle structure, pouring a polymer formulation on it, drying it, and peeling it from the inverse mold. Dissolving or hydrogel microneedles are manufactured using the solvent casting method with various types of polymers such as hydroxypropyl methylcellulose (Kim et al. 2016), hyaluronic acid (Du et al. 2019), CMC (Mistillis et al. 2015), polyvinyl pyrrolidone (Caffarel-Salvador et al. 2015; Tang et al. 2018; Tas et al. 2017), and poly(lactic-co-glycolic acid) (PLGA) (Li et al. 2019c).

Glass
Glass microneedles are primarily hollow and prepared using wet etching or micropipette puller (Dharadhar et al. 2019; Martanto et al. 2006). It exhibits sufficient strength for skin insertion, enabling easy processing of the tapered shape. It is easy to sterilize because it is stable at high temperature and pressure; the material itself is biocompatible. However, it breaks easily; specifically, if the tip of the microneedle is broken and it remains in the skin tissue, it can cause inflammation or granulomas.

Ceramic
Since ceramic materials such as alumina, calcium phosphate, and calcium sulphate exhibit biocompatibility and provide sufficient mechanical strength, studies have explored their use in the preparation of microneedles.