Nanomedicine for Oral Delivery: Strategies to Overcome the Biological Barriers

Oral drug delivery is highly desirable for medical intervention due to its convenience, patient adherence, and non-invasiveness. Despite significant efforts, the successful oral delivery of therapeutics and prophylactics has been largely hindered by biological barriers that limit bioavailability. Researchers have since turned to nanoparticles as promising delivery vehicles that offer tunable properties to protect therapeutic payloads and enhance transport across these barriers. In addition to material optimization and delivery strategies, biomimetic designs-particularly those inspired by viruses-have significantly advanced the field, leveraging natural mechanisms to penetrate mucosal layers through size, charge, and enzymatic functions. This review examines the key physiological challenges limiting oral drug absorption, including the harsh gastric environment, the mucosal layer, and the polarized epithelial barrier. Recent preclinical advancements are then highlighted in nanoparticle engineering aimed at overcoming these barriers and improving bioavailability. Continued innovation in oral nanomedicine holds immense potential to revolutionize treatment paradigms, enhancing both therapeutic efficacy and patient outcomes worldwide.