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本研究的目的是开发海藻酸包衣的壳聚糖纳米粒口服递送胰岛素。采用三聚磷酸钠(TPP)离子交联作用将N-[(2-羟基-3-三甲基铵)丙基]壳聚糖氯化物(HTCC)制备得到季铵化壳聚糖纳米粒(HTCC-T纳米粒),然后在温和搅拌条件下滴加入海藻酸钠溶液,进一步形成海藻酸包衣季铵化壳聚糖纳米粒(HTCC-A纳米粒)。分别采用粒度仪、透射电镜和HPLC分析对HTCC-A纳米粒进行了粒径、zeta电位、表面形态、载药量和包封率的表征。结果表明,HTCC-A纳米粒为均匀的球形颗粒,大小为(322.2±8.5)nm,表面带有正电荷((14.1±0.6)m V)。体外释放结果表明,在不同p H值的释放介质中,HTCC-A纳米粒的释放行为与HTCC-T纳米粒(未用海藻酸包衣)有很大的不同,这表明海藻酸包衣可以显著改善纳米粒中胰岛素的释放行为。同时,体外酶解试验和圆二色散图谱进一步证实,海藻酸包衣可以显著改善纳米粒中胰岛素结构稳定性。HTCC-A纳米粒十二指肠给药的相对药理生物利用度为8.0%±2.5%。与HTCC-T纳米粒口服给药相比,HTCC-A纳米粒的相对药理生物利用度显著增加(P<0.05),是HTCC-T纳米粒的2.2倍。由此可见,海藻酸包衣季铵化壳聚糖纳米粒(HTCC-A纳米粒)将可能成为一种有效的口服递送载体系统用于提高胰岛素的体内口服吸收效果。
The purpose of this study was to develop an alginate-coated chitosan nanoparticle for oral delivery of insulin. The quaternized chitosan nanoparticles were prepared from N - [(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) by sodium tripolyphosphate (TPP) HTCC-T nanoparticles), and then adding sodium alginate solution under mild agitation to further form alginate-coated quaternized chitosan nanoparticles (HTCC-A nanoparticles). The particle size, zeta potential, surface morphology, drug loading and encapsulation efficiency of HTCC-A nanoparticles were characterized by particle size analyzer, transmission electron microscope and HPLC respectively. The results showed that HTCC-A nanoparticles were uniform spherical particles with a size of 322.2 ± 8.5 nm and a positive charge of (14.1 ± 0.6) mV on the surface. The in vitro release results show that the release behavior of HTCC-A nanoparticles is quite different from that of HTCC-T nanoparticles (not coated with alginic acid) in the release medium with different p H values, indicating that the alginate coating can Significantly improve the release of insulin in the nanoparticles. At the same time, in vitro enzymatic hydrolysis test and circular dichroism spectroscopy further confirmed that alginate coating can significantly improve the structural stability of insulin in the nanoparticles. The relative pharmacological bioavailability of HTCC-A nanoparticles for duodenal administration was 8.0% ± 2.5%. Compared with oral administration of HTCC-T nanoparticles, the relative pharmacological bioavailability of HTCC-A nanoparticles was significantly increased (P <0.05), 2.2-fold that of HTCC-T nanoparticles. Thus, alginate-coated quaternized chitosan nanoparticles (HTCC-A nanoparticles) will likely serve as an effective oral delivery vehicle system for enhancing the oral absorption of insulin in vivo.