In vivo application of drug delivery systems faces inevitable challenges of numerous physiological barriers.Overcoming of these barriers often requires very different,or even contradictory properties of a drug delivery vehicle.Therefore,the in vivo applications of drug delivery systems are very limited.Recently,we developed several strategies to overcome these physiological barriers.Nanoparticles that possessed the ability to overcome both mucus barrier and epithelial barrier were developed,perfectly overcome the contradiction of these two barriers and thus efficiently improve the bioavailability of orally administered biomacromolecular drugs.