Oral Delivery of Biologics via the Intestine

Abstract

Biologics are currently one of the most promising avenues for therapeutic interventions in conditions such as metabolic disease, ageing and inflammatory disorders, and for chronic ailments, oral delivery of such medicines has for years been recognised as an important goal. Despite decades of intensive research, oral delivery of biologics is only just starting to prove feasible. There has been much talk about the barriers to uptake of biologics, and indeed, one function of the intestine is to prevent, in one way or another, passage of unwanted materials across the gut, and yet, grams of biological agents both large and small pass across the intestinal cell wall every day. This review first describes the functioning of the gut under normal circumstances, then identifies the principle biological mechanisms which have been harnessed successfully, to date, to achieve oral uptake, outlining the pros and cons of each approach. Examples with different biologics are given, and information on result of the latest clinical trials is provided, where available.

Three-Dimensional Printing of a Container Tablet: A New Paradigm for Multi-Drug-Containing Bioactive Self-Nanoemulsifying Drug-Delivery Systems (Bio-SNEDDSs)

“…The delivery of biologics via an oral route would be possible using this approach, while encasing it inside a suitable system that prevents its degradation and maintains the integrity and stability. The conversion of large molecules, proteins, and biologics to solid powders using lyophilization techniques lead to loss inactivity and, therefore, most biologics are administered via intravenous routes or formulated into lipid nanoparticles [ 43 , 44 , 45 , 46 ]. These liquid-phase systems can be delivered similarly, as demonstrated in this study.…”

Future Perspectives of Oral Delivery of Next Generation Therapies for Treatment of Skin Diseases

“…The harsh environment of the gastrointestinal tract including its high enzymatic activity and abrupt pH triggers drug degradation and writes off the drug’s pharmacodynamics. Moreover, the impermeability of the intestinal cells to large molecules and the diffusion impairment posed by the mucin layer contribute to hindering the absorption into the bloodstream of peptides, proteins, monoclonal antibodies, and other large molecules [ 121 ]. For this reason, injections and intravenous infusions are needed to ensure that they reach systemic circulation unaltered.…”

Re-Assessing PK/PD Issues for Oral Protein and Peptide Delivery

“…Very large molecules may distribute preferentially to lymphatic relative to blood vessels, but the size for such a discrimination in the intestinal villus has not been described as yet. Based upon these potential differences in fate between hydrophobic versus hydrophilic molecules absorbed in the GI tract, the fate of biopharmaceuticals absorbed into the lymph would more closely match the PK profile from a parenteral administration, such as an SC injection [ 23 ]. Thus, if it is critical to mimic the PK profile that is demonstrated by an SC injection, oral delivery that results in lymphatic uptake and not uptake into the hepatic portal vasculature may be a preferable outcome ( Figure 1 c).…”