Division of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
Int J Biol Macromol. 2013 Oct;61:363-72. doi: 10.1016/j.ijbiomac.2013.08.002. Epub 2013 Aug 8.
The aim of the study is to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on thiolated chitosan for oral insulin administration. The preparations were characterized by particle size, entrapment efficiency, stability and drug release. Serum insulin concentrations were determined after oral administration of all formulations. Insulin SNEDDS formulation was served as control. The optimized SNEDDS consists of 65% (w/w) miglyol 840, 25% (w/w) cremophor EL, 10% (w/w) co-solvents (a mixture of DMSO and glycerol). The formulations in the presence or absence of insulin (5mg/mL) were spherical with the size range between 80 and 160 nm. Entrapment efficiency of insulin increased significantly when the thiolated chitosan was employed (95.14±2.96%), in comparison to the insulin SNEDDS (80.38±1.22%). After 30 min, the in vitro release profile of insulin from the nanoemulsions was markedly increased compared to the control. In vivo results showed that insulin/thiolated chitosan SNEDDS displayed a significant increase in serum insulin (p-value=0.02) compared to oral insulin solution. A new strategy to combine SNEDDS and thiolated chitosan described in the study would therefore be a promising and innovative approach to improve oral bioavailability of insulin.
本研究旨在开发一种基于巯基化壳聚糖的自微乳给药系统(SNEDDS)用于口服胰岛素给药。通过粒径、包封效率、稳定性和药物释放来对制剂进行表征。所有制剂口服后均测定血清胰岛素浓度。胰岛素 SNEDDS 制剂作为对照。优化的 SNEDDS 由 65%(w/w)miglyol 840、25%(w/w)cremophor EL 和 10%(w/w)共溶剂(DMSO 和甘油的混合物)组成。存在或不存在胰岛素(5mg/mL)的制剂均为粒径在 80 至 160nm 之间的球形。与胰岛素 SNEDDS(80.38±1.22%)相比,当使用巯基化壳聚糖时,胰岛素的包封效率显著提高(95.14±2.96%)。30 分钟后,与对照相比,胰岛素从纳米乳中的体外释放曲线明显增加。体内结果表明,与口服胰岛素溶液相比,胰岛素/巯基化壳聚糖 SNEDDS 使血清胰岛素显著增加(p 值=0.02)。因此,本研究中描述的将 SNEDDS 与巯基化壳聚糖相结合的新策略可能是提高胰岛素口服生物利用度的一种有前途和创新的方法。