PEGylated solid lipid nanoparticles containing saquinavir were prepared by a solvent diffusion method combined with ionic complexation, and exhibited a higher drug encapsulation efficiency, drug loading capacity and slowed drug release behavior. Moreover, the nanoparticles presented low cytotoxicity, higher transport ability across intestinal epithelial cells, and hence higher relative bioavailability which increased with enhancing of the polyethylene glycol content in the nanoparticles.