温度敏感凝胶介导的氟尿嘧啶复乳经Caco-2细胞模型的转运吸收研究

Transportation and Absorption of Thermo-sensitive Gel Mediated 5-FU Multiple Emulsion in Caco-2 Cell Monolayer Model

目的:制备携带氟尿嘧啶(5-FU)复乳的温度敏感凝胶,采用Caco-2细胞模型考察其转运吸收特性。方法:采用两步复乳法制备5-FU复乳,以泊洛沙姆407为温敏凝胶材料、海藻酸钠为生物粘附材料,制备携带5-FU复乳的温度敏感凝胶。建立跨Caco-2细胞转运模型,测定其跨生物膜转运、吸收率。结果:5-FU复乳温度敏感凝胶在室温下为固态,10℃条件下转变为自由流动的液态,其跨Caco-2细胞表观渗透系数Papp值为(1.47±0.11)×10-5(cm·s-1),细胞摄取率为(17.1±0.24)%,与5-FU水溶液相比,其跨膜转运率提高了约6倍(P<0.01),细胞摄取率提高了约3.9倍(P<0.01)。结论:5-FU复乳温度敏感凝胶结合了微乳剂与温度敏感凝胶剂的特点,既适用于直肠原位给药,又可增加药物于病灶部位的吸收效率,将为直肠癌的治疗提供新的有效途径治疗策略。

Objective： To develop 5-FU multiple emulsion entrapped into thermo-sensitive gel （5-FU-DEG） and detect the ab- sorption and transportation in Caeo-2 cell monolayer model. Methods ： The 5-FU multiple emulsion was prepared by a two-step emulsif- ying method. Poloxamer 407 （P407） was used as the thermo-sensitive material and sodium alginate （SA） was used as the bioadhesive material for the preparation of 5-FU-DEG. Caco-2 cell monolayer model was used to investigate the transportation and absorption of 5- FU. Results： 5-FU-DEG gelled at the ambient temperature and turned into liquid below 10℃ The apparent permeability coefficient （Papp） of 5-FU-DEG was 1.47±0.11×10^-5（cm·s^-1）, which was about 6 times higher than that of 5-FU water solution（2.39±0.21×10^-6cm·s^-1） （P 〈0.01 ）. The cellular uptake rate of 5-FU-DEG was （ 17.1±0.24） %, which was 3.9 times greater than that of 5-FU water solution （4.41 ±0.23% ）（P 〈 0.01 ）. Conclusion： 5-FU-DEG can efficiently enhance the transportation and absorption of drug in rectal site by using micro-emulsion technology combined with thermo-sensitive technology, which can be an effective rectal delivery system for 5-FU to treat rectal cancer.