Biological drugs have rapidly become an important therapeutic modality in the last decade because of their100% bioavailability, high potency, high specificity, and desirable safety profile. From a global point of view, more than half of the current top 20 blockbuster drugs are biopharmaceuticals (Sagonowsky, 2021). The success of protein, peptide, and antibody-based therapies is evident—the biopharmaceuticals market is predicted to reach $388 billion by 2024 (Liang et al., 2020). Protein and peptide-based drugs are now widely used as the first-line treatments for a wide range of diseases, such as type I diabetes, rheumatoid arthritis, specific cancers, and hemophilia (Kirkby et al., 2020). Due to most biopharmaceuticals are peptide and protein-based, which leads to poor oral bioavailability, the intravenous route is still the main strategy for drug delivery. Unfortunately, the injection pain may translate to reluctance for the patients to choose biopharmaceuticals. In a more severe situation, repeated administration may lead to phlebitis, tissue necrosis, and toxic adverse effects.
Researchers have been exploring various non-invasive strategies for protein drug delivery, and the microneedle (MN) patches are one of the options. The patch has multiple micro-projections assembled on one side of a supporting base, and the projection height can be between 25 to 900 μm. The micro-projections can painlessly penetrate the stratum corneum (outermost layer of the skin) and facilitate transdermal drug delivery by creating temporary microscopic aqueous channels (Kirkby et al., 2020). While making the medicine application process less painful, the MN patches are also favored by the pharmaceutical manufacturers, as of their low cost in bulk production and long-term safety.
The concept of MN was first brought up by Gerstel and Place in 1971. It was later practically realized in 1998 due to the lack of advancement in microfabrication techniques. Today, MN technology has developed further, and they are traditionally placed in five different categories: solid, coated, hollow, dissolving, and hydrogel-forming, as in Figure 1 (Kirkby et al., 2020).
Fig.1 Representation of skin MN application transdermal drug delivery. *stratum corneum,**epidermis.(A) Solid MN that is applied and removed, followed by application of the formulation. (B) Solid MN is coated with drugs for instant delivery. (C) The drug is mixed with soluble MNs that dissolve in interstitial fluid. (D) Hollow MNs puncture the skin, after which liquid drug can be actively infused. (E) Hydrogel-forming MNs withdraw skin interstitial fluid upon skin punctuation. This induces drug diffusion through the swollen micro-projections.
The advantages of MNs over traditional routes of drug delivery (intramuscular injection, oral intake) are apparent, and MNs are highly likely to be used as a drug delivery strategy in the next decade. The use of MNs could vastly improve the quality of life for patients, improve public health, and increase the economic productivity of developing countries. For the future success of MNs, the long-term safety validation, methods of manufacture, and their ability to comply with standardized GMP guidelines should be fully studied. Furthermore, marketing strategies will also be vital in achieving maximum market share relative to existing and widely accepted conventional delivery systems. In the meantime, academia and industry must work together to address concerns and thereby push MN technology into the clinic, where its potential can be truly realized.
Liang, W., Pan, H. W., Vllasaliu, D., & Lam, J. K. (2020). Pulmonary delivery of biological drugs. Pharmaceutics, 12(11), 1025.
Sagonowsky, E.(2021). https://www.fiercepharma.com/special-report/top-20-drugs-by-2020- sales
Bajracharya, R., Song, J. G., Back, S. Y., & Han, H. K. (2019). Recent advancements in non-invasive formulations for protein drug delivery. Computational and structural biotechnology journal, 17, 1290-1308.
Kirkby, M., Hutton, A. R., & Donnelly, R. F. (2020). Microneedle mediated transdermal delivery of protein, peptide, and antibody-based therapeutics: current status and future considerations. Pharmaceutical Research, 37, 1-18.