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Oral administration of nanomedicines offers a promising non-invasive drug delivery platform, with advantages in patient compliance and administration convenience. However, its clinical translation in gastrointestinal (GI) and extraintestinal diseases is limited by multiple physiological and pharmacokinetic barriers, including harsh gastrointestinal environments, poor translocation between mucus and epithelial layers, rapid clearance by the liver and kidneys, limited tissue accumulation, low cellular uptake efficiency, insufficient lysosomal escape, and suboptimal intracellular drug release. These challenges collectively lead to low oral bioavailability and limited therapeutic efficacy. This review comprehensively summarizes the latest progress in oral nanomedicine, defines six key attributes for effective GI-targeted drug delivery and eight system application design principles. We also discuss the transformation bottlenecks and emphasize emerging strategies to overcome these obstacles, and provide insights into the integration of oral nemonium drugs with precision medicine.
This study was published in ACS Nano under the title "Design Principles of Oral Nanomedicines to Overcome the Delivery Barriers".
References: DOI: 10.1021/acsnano.5c14045
