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As a useful alternative drug carrier system to emulsions,liposomes and polymeric nanoparticles,solid lipid nanoparticles(SLN)are a colloidal drug delivery system prepared by replacing the liquid lipid of an O/W emulsion by a solid lipid or a blend of solid lipids,i.e.the lipid particle matrix being solid at both room and body temperature.Compared to other system,SLN has many advantages,such as good biocompatibility,simple preparation process,easy large-scale production,controlled release and targeting delivery,etc.However,some disadvantages are also associated with SLN.One main problem of SLN is its poor physical stability.The lipid matrix of SLN may undergo a polymorphic transition from higher energy crystal modifications to lower energy and more ordered modifications during storage,which leads to a possible undesirable drug expulsion due to formation of more perfect crystalline lattice.To improve the physical stability of SLN,N-Trimethyl-N-octyl chitosan(TMACS)was synthesised and used as a emulsifier for the preparation of solid lipid nanoparticles(TMACS-SLN)in present study.TMACS-SLN was prepared using high-speed homogenizer and ultrasonic probe.The effects of several variables including ultrasound power and time,the ratio of the lipid to TMACS were investigated.The SLN could be successfully prepared with small and uniform particle size when the ultrasonic power and time were 600 W and 6 min respectively,and the ratio of the lipid to TMACS was optimazed to be 1:1.The morphology and particle size of nanoparticles were examined by transmission electron microscope and zetasizer,respectively.The results showed that the appearance of TMACS-SLN was spherical with the mean particle size below 300 nm.The particle size of TMACS-SLN was uniform with PDI below 0.5.Its zeta potentials exceeded+30 mv.The results from DSC,X-ray and FT-IR study of the fresh nanoparticles indicated that the capacity of TMACS to reduce crystallinity of lipid was higher compared with Poloxamer 188.The result from the determination of the emulsifying activity index(EAI)illuminated that TMACS showed excellent surface active.The results obtained from the stability tests showed that no significant crystal transition of TMACS-SLN was observed during 6 months storage at 25℃ or 4℃ conditions.However,to a certain extent,the lipid crystal of SLN prepared using Poloxamer 188 as the emulsifier at the same process parameters as TMACS-SLN,transformed from metastable modification to stable modification during 6 months storage at 25℃ or 4℃ conditions.This elucidated that SLN using TMACS as the emulsifier showed better physical stability compared with Poloxamer 188 as the emulsifier.TMACS possessed higher activity to inhibit the crystal transition of the lipid in SLN than Poloxamer 188.