Dissolving microneedles as emerging tools in delivery of biological macromolecules: Current practices and future opportunities

In recent years, biological macromolecules (BMs) such as proteins, peptides, nucleic acids, carbohydrates, hormones, and lipids, have been extensively explored for the effective treatment of cancer, diabetes, and chronic infectious diseases such as Human Immunodeficiency Virus infection, Influenza, Hepatitis B, etc. These molecules present several physicochemical and biological challenges when administered through conventional drug delivery routes such as oral, subcutaneous, and intramuscular administration. Enzymatic degradation, hepatic first-pass metabolism, and poor oral bioavailability are major limitations of the oral route. Parenteral routes, such as subcutaneous and intramuscular administration, are invasive approaches that compromise patients’ compliance. Similarly, the permeation of BMs via skin barriers affects their delivery via transdermal or topical route. Hence, an innovative treatment strategy is required to successfully deliver the aforementioned cargo for effective treatment of diseases without posing any limitations as mentioned for existing treatment options. This objective can be achieved by tailoring BMs loaded with dissolving microneedles. Dissolving microneedles are reported to successfully deliver BMs by overcoming limitations of existing delivery routes with minimal invasion that is painless. This review explores the advancements in preclinical and clinical applications of BM-loaded dissolving microneedles, along with the challenges associated with the treatment of cancer, infectious diseases, and degenerative diseases.