蜂蜡含量对纳米结构脂质载体消化释放行为及巨噬细胞摄取率的调控影响

Modulatory Effect of Beeswax Content on the Digestive Release and Macrophage Uptake of Nanostructured Lipid Carriers

脂质相组成对纳米结构脂质载体(nanostructured lipid carriers,NLCs)消化释放行为和巨噬细胞摄取具有调控作用。本实验通过体外模拟消化实验、离体肠黏附渗透实验和RAW264.7小鼠巨噬细胞摄取实验探究脂质相中蜂蜡质量比对NLCs物性、脂质消化、姜黄素释放、小肠黏附渗透以及巨噬细胞摄取效率的影响。结果显示:随脂质相中蜂蜡含量的增加,NLCs粒径增加,负载率及包封率均有所提高。相比未添加蜂蜡的NLC0(其油相为中链脂肪酸甘油三酯),油相中添加5%(质量分数,下同)或10%蜂蜡(NLC5和NLC10)提升了NLCs表观黏度和物理稳定性,增强了小肠黏膜黏附渗透效率(NLC5和NLC10组姜黄素在上皮组织细胞的荧光信号强度比NLC0组分别提高了20.27%和55.02%)。随蜂蜡含量增加,NLCs的脂解效率、游离脂肪酸(free fatty acid,FFA)释放速率和姜黄素释放量均有所下降(FFA释放速率KNLC0(0.13 min^(-1))>KNLC5(0.08 min^(-1))>KNLC10(0.06 min^(-1)));姜黄素释放量RNLC0((99.93±0.09)%)>RNLC5((96.38±0.05)%)>RNLC10((90.05±0.05)%),体现出缓释的特性。相比游离的姜黄素,NLCs促进了姜黄素在RAW264.7小鼠巨噬细胞内富集(增强了5.68~6.25倍)。本研究可为蜂蜡基NLCs在亲脂活性成分口服递送和健康效应调控的应用提供指导。

Lipid phase composition of nanostructured lipid carriers(NLCs)modulates their digestive release behavior and cellular uptake by macrophage.In this study,the effects of the percentage of beeswax in the binary lipid mixture on the physical properties,lipid digestion,curcumin release,intestinal adhesion and penetration,and macrophage uptake of NLCs were investigated by in vivo simulated digestion,ex vivo intestinal adhesion and penetration and RAW264.7 mouse macrophage uptake experiments.The results showed that the particle size,loading efficiency and encapsulation efficiency of NLCs increased with an increase in the percentage of beeswax in the lipid phase.Compared with NLCs without beeswax(NLC0),whose oil phase consisted of medium chain fatty acid triglycerides(MCT),addition of 5%or 10%beeswax to MCT significantly improved the apparent viscosity,physical stability,intestinal mucosal adhesion and penetration of NLCs(the fluorescence signal intensity of curcumin in epithelial cells increased by 20.27%and 55.02%,respectively).Additionally,with an increase in beeswax content,the lipolysis efficiency,the release rate of free fatty acid(FFA)and the amount of released curcumin from NLCs decreased significantly;the release rate of FFA decreased in the following order:KNLC0(0.13 min^(-1))>KNLC5(0.08 min^(-1))>KNLC10(0.06 min^(-1)),and the amount of released curcumin declined in the following order:RNLC0((99.93±0.09)%)>RNLC5((96.38±0.05)%)>RNLC10((90.05±0.05)%),indicating sustained release characteristics.Compared with free curcumin,NLCs promoted the enrichment of curcumin in RAW264.7 macrophages by 5.68-6.25 times.These findings can provide guidance for the application of beeswax based NLCs in oral delivery of lipophilic active ingredients and regulation of health effects.