Solid lipid nanoparticles modified with amphipathic chitosan derivatives for improved stability in the gastrointestinal tract

Abstract

In order to reduce enzymatic degradation and thereby improve the stability of solid lipid nanoparticles (SLNs) in the gastrointestinal tract (GIT), two comb-shaped amphiphilic macromolecular materials of N-stearyl-N-trimethyl chitosan (STMC) and N-linoleoyl-N-trimethyl chitosan (LTMC) were fabricated as emulsifier to modify SLNs. Some influence factors of lipolysis medium were investigated to establish in vitro lipolysis model for SLNs. The results showed that the lipolysis curves were fluctuant and variable when the amounts of SLNs were low. The lipolysis of SLNs increased with pancreatic enzyme activity ascending from 150 to 450 USPU/mL and achieved a threshold between 450 and 600 USPU/mL. The lipolysis of STMC-SLNs increased with the initial calcium concentration rising from 0 to 1.4 mM, but had no obvious change from 1.4 to 5 and 10 mM. Besides, SLNs lipolysis increased with bile acid salt and phospholipid concentration increasing. Finally, SLNs stability in GIT was tested with the optimized in vitro lipolysis model. The results revealed that as compared to P188-SLNs and Tween-SLNs, STMC-SLNs lipolysis decreased by 27.33% and 48.55%, and LTMC-SLNs decreased by 22.64% and 43.86%, respectively. Besides, the drug precipitations for STMC-SLNs and LTMC-SLNs were significantly decreased. These results demonstrated that both STMC-SLNs and LTMC-SLNs had excellent gastrointestinal stability.