Improved gastrointestinal stability of solid lipid nanoparticles using comb-shaped amphiphilic inulin derivatives.

Abstract

In order to reduce enzymatic degradation and thereby enhance the stability of solid lipid nanoparticles (SLNs) in the gastrointestinal tract, comb-shaped amphiphilic macromolecular material (CAM) of dodecyl inulin (Inu12) and octadecyl inulin (Inu18) were designed as the emulsifier and stabilizer to modify SLNs (Inu12/Inu18-SLNs). Inu12-SLNs and Inu18-SLNs had similar particle size as the control SLNs (P188-SLNs and Tween-SLNs) prepared with the straight chain surfactants, poloxamer 188 and tween-80 as the emulsifier, which ranged from 220 nm to 270 nm. The zeta potentials of all the SLNs formulations were slightly negative. Cyclosporine A (CsA)-loaded Inu12-SLNs and Inu18-SLNs showed a much lower drug release than CsA-loaded Tween-SLNs at pH 6.8 PBS containing 0.1% sodium dodecylsulfate and all the three SLNs exhibited biphasic release profiles. The results of cytotoxicity test showed that the toxic effects of Inu12-SLNs and Inu18-SLNs on cell viability had no significant difference in comparison to P188-SLNs and Tween-SLNs. Both CAM-modified SLNs (Inu12/Inu18-SLNs) showed a significant reduced lipolysis in vitro. As compared to P188-SLNs and Tween-SLNs, the total lipolysis of Inu18-SLNs during 4 h was decreased by 31.51 % and 45.67 % and that of Inu12-SLNs was decreased by 24.13 % and 38.29 %, respectively. Besides, the cumulative drug precipitations for CsA-loaded Inu12-SLNs and Inu18-SLNs during 4 h lipolysis were dramatically declined, which were 64% and 42% of that for Tween-SLNs, respectively. Therefore, it can be concluded that both alkylated inulin-derived CAM-modified SLNs, especially the Inu18-SLNs had the improved gastrointestinal stability to resist the lipid degradation by lipase enzyme.