Comparison of the oral bioavailability of silymarin-loaded lipid nanoparticles with their artificial lipolysate counterparts: implications on the contribution of integral structure.

Both solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were artificially broken down into lipolysates. Their oral bioavailability, with silymarin as a model drug, was compared in dogs to highlight the contribution of their integral structure. The lipid nanoparticles were prepared using a conventional hot homogenization method, whereas the lipolysates were obtained through lipolysis in phospholipid- and bile salt-enriched simulated intestinal fluid. More than 80% of vehicle-associated drugs could be transformed into the water-soluble form of mixed micelles. Pharmacokinetics analysis in dogs showed a decrease in bioavailability of 74.86% and 59.09% for lipolysates compared to integral NLCs and SLNs, respectively. It was indicated that lipolysates contributed to a majority of drug absorption. Integral nanoparticles were superior to their lipolysate counterparts, but only marginally; if the approximately 20% of the drug that precipitated during in vitro lipolysis was deducted from the overall absorption amount, the superiority of integral nanoparticles would be significantly compromised. In conclusion, lipolysis was the predominant in vivo absorption mechanism, and the contribution of intact lipid nanoparticles was limited.