Polymeric Matrix Systems for Non-Invasive Oral Delivery of Macromolecular Therapeutics: Recent Advances and Future Perspectives

Peptides, proteins, oligonucleotides and vaccine antigens are important therapeutic molecules because they can act on specific targets in the body. However, many of these medicines are given by injection because the gastrointestinal (GI) tract can damage them or prevent them from reaching the bloodstream. Stomach acid, digestive enzymes, mucus, the intestinal lining, drug efflux and metabolism before the drug reaches the circulation all limit oral absorption.[1–6] Polymeric matrix systems are being investigated as a way to protect these molecules, control drug release and help formulations reach the intended part of the GI tract.[7–14] This review discusses natural, semi-synthetic and synthetic polymers, along with tablets, hydrogels, films, micro- and nanoparticles, and combined delivery systems. It also considers manufacturing, quality testing, drug-release models and the challenges involved in translating laboratory findings into clinical use. Chitosan, alginate, pectin, cellulose derivatives, polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA) and pH-responsive polymers each offer useful properties, such as mucoadhesion, swelling, degradation or site-specific release.[8–18] Despite these advantages, improved protection or movement through a laboratory model does not guarantee effective absorption in humans. Oral semaglutide demonstrates that a particular peptide can be administered orally when the formulation is carefully designed and includes an absorption enhancer. It does not establish that polymer matrices alone can make all biological medicines suitable for oral use.[19,20] Future progress will require drug-specific formulation design, reliable manufacturing, tests that confirm biological activity, realistic laboratory models and stronger links between in-vitro results and drug behaviour in people.