研究了一种用T型微通道制备固体脂质纳米粒(solid lipid nanoparticles,SLN)的新方法。以softisan100(C10-C18的混合脂)丙酮溶液作为脂相,以Poloxamer 188水溶液为水相,用注射泵分别将脂相和水相注入T型通道的主道和支道内,两相在交叉口接触后形成明显的相界面,并继续沿主道向前流动。脂相中丙酮通过相界面迅速向水相扩散,随着流体的向前运动,脂相中脂的浓度不断增大至过饱和而形成固体脂质纳米粒(SLN)。实验考察了两相流速和微通道尺寸对SLN粒径大小和粒径分布的影响。结果表明:在实验条件下,制得的SLN粒径在110~350nm之间,多分散性指数小于0.24;T型通道交叉口的流场分布受两相相对流速的影响,并直接影响成粒规律,在不出现两相返混条件下,保持水相流速不变,SLN粒径随脂相流速增大而增大;保持脂相流速不变,粒径随水相流速的增大略有增大;通道尺寸越小所制得粒径也越小。
A new method of preparing solid lipid nanoparticles (SLN) by using T-shaped junction microchannel was proposed. The lipid solution formed by dissolving Softisan 100 (triglyceride mixture of fatty acids with chain lengths of C10 to C18) into acetone was used as lipid phase, and the surfactant solution formed by dissolving Poloxamer 188 into super pure water was used as aqueous phase; then they were injected into the main channel and branch channel of the T-shape junction microchannel, separately, by precision syringe pumps. The two phases injected meet at the junction of the T-shaped microchannel and form interface of phases. The solvent acetone in the lipid phase diffuses quickly into the aqueous phase through the interface, which causes the supersaturation of lipid and the formation of SLN. The effects of various operation conditions, such as various flow velocities of both lipid and aqueous phases and different dimensions of the microchannel, on the size and the polydispersity of the formed SLN were investigated. Under our experimental conditions, SLN with small size of 110 -350 nm and narrow size distribution (polydispersity less than 0.24) were prepared successfully. The experimental results show that the flow field distribution at the T-junction is affected by the flow rates of the two phases, which also affect the diameter and size distribution of the prepared SLN obviously. Under the condition of not occurring backmixing of the two injected phases, the size of the prepared SLN increases with the increase of the aqueous phase velocity when the lipid phase velocity keeps unchanged, while it increases slightly with the increase of the lipid phase velocity when the aqueous phase velocity keeps unchanged. It was also found that the prepared SLN with smaller particle size could be obtained when a T-shaped microchannel with narrower main channel was used.