Surface Chemistry-Based Nanomedicine Design in Oral Drug Delivery

Abstract

Surface modification of nanomedicines represents a widely employed strategy to augment their performance and endow them with additional functionalities beyond their intrinsic properties. To circumvent the obstacles imposed by the gastrointestinal tract, a growing body of research has focused on interfacial chemical modifications to improve oral drug delivery. By tailoring surface chemistry, these modifications can mitigate drug degradation, enhance mucus permeability, and facilitate transcellular or paracellular transport across the intestinal epithelium, thereby ultimately improving oral bioavailability and expanding the therapeutic potential of nanomedicines. This review first outlines the major physiological barriers to oral drug delivery. Subsequently, it introduces and discusses the corresponding surface chemistry-based nanomedicine design strategies for overcoming these barriers and summarizes the relevant design principles and structure-function relationships. Finally, the review offers insight into the challenges and prospects, aiming to guide the rational design of surface chemistry-engineered nanomedicines for oral drug delivery.