Mechanisms for oral absorption enhancement of drugs by nanocrystals

Currently, numerous new compounds suffer from poor water solubility, hindering their oral absorption from the gastrointestinal tract and thereby limiting their clinical application. Nanocrystal technology, with more than 10 products on the market, is one of the favored pharmaceutical technologies for the enhancement of oral bioavailability. However, this technology has a limited ability of bioavailability enhancement for several drugs; therefore, a good understanding about the absorption mechanisms of nanocrystals in the gastrointestinal tract is urgently needed. In this review, the mechanisms of nanocrystals for improving the bioavailability of poorly soluble drugs were summarized from four aspects: enhanced solubility and dissolution rate, enhanced interaction with mucus layer, enhanced transport across the intestinal membrane and enhanced absorption by stabilizers. In addition, the factors that impact the absorption of nanocrystals were also reviewed. We believe that this paper will help scientists understand the in vivo performance of nanocrystals in the gastrointestinal tract and design novel strategies for further improving the bioavailability of nanocrystals.