Enzymatic Degradation of Dynasan 114 SLN – Effect of Surfactants and Particle Size

Abstract

The degradation velocity of solid lipid nanoparticles (SLN) is – apart from drug diffusion – an important parameter determining drug release in vivo. To assess the effect of stabilizers systematically, Dynasan 114 SLN were produced with ionic surfactants (e.g. cholic acid sodium salt (NaCh), sodium dodecyl sulfate (SDS), cetylpyridiniumchloride (CPC)) and steric stabilizers (Tween 80, Poloxamer 188, 407 and Poloxamine 908) including a mixture of cholic acid sodium salt and Poloxamer 407. In addition, the size effects were investigated. The degradation velocity was measured using an in vitro lipase assay. SLN stabilized with lecithin and NaCh showed the fastest, Tween 80 the intermediate and the high molecular weight Poloxamer 407 the slowest degradation. Size effects were less pronounced for fast degrading particles (e.g. those stabilized with NaCh). No difference in the size range of 180–300-nm was observed, but a distinctly slower degradation of 800-nm SLN could be detected. For slowly degrading particles, more pronounced size effects were found. Size effects are more difficult to assess when the PCS diameters are similar, but small fractions of micrometer particles are present, besides the nanometer bulk population. The measured FFA formation is then a superposition of particles degrading at different speeds due to differences in the shape of the size distribution. Admixing of Poloxamer to NaCh had no delaying effect on the degradation of the Dynasan 114 SLN, indicating an influence of the nature of the lipid matrix that is affecting the stabilizers affinity to and anchoring onto the SLN surface.