Silica nanoparticles: A promising platform for enhanced oral delivery of macromolecules

Oral ingestion remains as the most convenient route of administration for the application of pharmaceuticals since it is non-invasive and does not require trained personnel to administer the drugs. Despite significant progress in novel oral drug delivery platforms over the past few decades, the oral delivery of macromolecules (particularly for peptides and proteins) is one of the major challenges faced by the biopharmaceutical industry. This is even more important since a large number of biologic drugs have been available in the past decade which typically require intravenous administration. Recently, silica nanoparticles have emerged as multifunctional, biocompatible and biodegradable inorganic nanocarriers with enormous potential as an oral drug delivery platform for various therapeutics including macromolecules. Their unique structural composition facilitates the loading of large therapeutic payloads at desired loading capacities for a controlled and site-specific oral delivery. Here, we review first the physiological challenges for oral delivery of peptides and proteins. Next, we discuss silica-based functional materials for oral delivery of macromolecules and highlight their evolving role not only as an encapsulant but as a permeation enhancer as well. Lastly, we also discuss potential strategies for future translation of these novel materials to the clinic.