目的研究不同季铵化度(DQ)对三甲基壳聚糖(TMC)载胰岛素纳米粒性质及细胞摄取、跨膜转运的影响,并考察黏液对其作用,为口服纳米粒研究提供参考。方法采用离子交联法制备不同季铵化度三甲基壳聚糖纳米粒,以黏液分泌型HT29-MTX.E12(E12)细胞为模型研究在有无黏液存在的情况下纳米粒的细胞摄取与转运情况。结果季铵化度越高,三甲基壳聚糖纳米粒稳定性、细胞摄取及跨膜转运率越高,并且黏液对高季铵化度的三甲基壳聚糖纳米粒表现出阻碍作用,对低季铵化度的三甲基壳聚糖纳米粒表现为一定的促进作用。结论季铵化度是影响三甲基壳聚糖纳米粒性质的关键因素,在设计口服纳米粒时要综合考虑其穿黏液性质和跨肠上皮细胞的能力。
OBJECTIVE To study the effects of degree of quaternization (DQ) and mueus on cellular uptake and transport of tri- methyl chitosan (TMC) nanoparticles. METHODS Ionotropic gelation method was adopted to prepare TMC nanoparticles, and mu- cus-secreting HT29-MTX-E12 (El2) cell monolayer was chosen as a cell model to investigate the cellular uptake and transport of TMC nanoparticles with or without mucus. RESULTS The efficiency of cellular uptake and transport as well as the stability of TMC nanop- articles were enhanced with DQ increasing. Mucus acted as a barrier to TMC nanoparticles with higher DQ while as an enhancer to TMC nanoparticles with lower DQ. CONCLUSION DQ is a key factor to impact properties of TMC nanoparticles. Both mucus pene- trating ability and gut epithelium permeation should be considered.