Trends and Technologies for Oral Delivery of Macromolecules

As part of this Research Topic, we are hosting a panel discussion and public Q&A, featuring Prof. David Brayden (University College Dublin), Dr. Driton Vllasaliu (King’s College London) and Dr. Andrew Lewis (Chief Scientific Officer, Quotient Sciences) on the 13th May 2026 at 14:00 UTC (coordinated time). Register your attendance using the link here.Oral administration of macromolecules covers the categories of peptides, proteins, RNA, PROTACS, and monoclonal antibodies amongst others. On the peptide side, there have been eight FDA approvals for oral administration to achieve systemic bioavailability, with three formulated with permeation enhancers. Apart from cyclosporine and voclosporin, bioavailability levels from such formulations hover around 1%, which limits candidates to potential stable molecules, ideally with long half-lives. There is a need for new candidate peptides with lower molecular weight (exemplified by macrocycles), new enhancers, and new tablet designs. Challenges for orally administering large molecules such as proteins and antibodies are higher, and device-led approaches seem to be better suited for these macromolecules than standard enhancer formulations or nanotechnology.The topic's goal is to assess current approaches and technologies to orally-administer macromolecules with realistic chances of success. Much of the literature has focussed to date on oral GLP-1 RAs peptides, but there are other peptides that are under consideration and also other classes of macromolecules that can benefit from the oral route of administration, including PROTACS, RNA, and bi-specific antibodies. Of interest is hearing the patient perspective on oral administration of particular macromolecules, with the realisation that complex oral daily dosing requirements can reduce adherence, particularly for chronic disease indications. We invite papers in the following areas:• Mechanistic understanding of enhancer action in the stomach and small intestine• New enhancers and enhancer combinations• Nanotechnology that can facilitate intestinal absorption of macromolecules• Potential ingestible device options that employ physical disruption of the epithelium• In vitro, ex vivo, and in vivo demonstration of new technology efficacy and safety• Pharmacokinetic and pharmacodynamic relationships describing oral administration and blood levels• Use of AI in screening formulations for oral administration of biologics• Clinical trial data to show proof-of principle• Safety methodology to assess oral formulations in the GI tract• Tablet and capsule design using multiple modes of synthesis that demonstrate desired release profiles in vitro and in vivo.• Tools that predict or guide performance of oral biologic formulations in the GI tract• Organoid and intestine-on-a chip models demonstrating guidance in oral formulation performance• Preclinical models for oral peptide deliveryTopic Editor Andrew Lewis is employed by Quotient Sciences. All other Topic Editors declare no competing interests with regards to the Research Topic subject. Topic editors: Driton Vllasaliu, David J Brayden, Andy Lewis Source: https://www.frontiersin.org/research-topics/78792/trends-and-technologies-for-oral-delivery-of-macromolecules