Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery.

Advancements in biotechnology and protein engineering expand the availability of various therapeutic proteins including vaccines, antibodies, hormones, and growth factors. In addition, protein drugs hold many therapeutic advantages over small synthetic drugs in terms of high specificity and activity. This has led to further R&D investment in protein-based drug products and an increased number of drug approvals for therapeutic proteins. However, there are many biological and biopharmaceutical obstacles inherent to protein drugs including physicochemical and enzymatic destabilization, which limit their development and clinical application. Therefore, effective formulations of therapeutic proteins are needed to overcome the various physicochemical and biological barriers. In current medical practice, protein drugs are predominantly available in injectable formulations, which have disadvantages including pain, the possibility of infection, high cost, and low patient compliance. Consequently, non-invasive drug delivery systems for therapeutic proteins have gained great attention in the research and development of biomedicines. Therefore, this review covers the various formulation approaches to optimizing the delivery properties of protein drugs with an emphasis on improving bioavailability and patient compliance. It provides a comprehensive update on recent advancements in nanotechnologies with regard to non-invasive protein drug delivery systems, which is also categorized by the route of administrations including oral, nasal, transdermal, pulmonary, ocular, and rectal delivery systems.