Prego C, Torres D, Alonso M J
Department of Pharmaceutical Technology, University of Santiago de Compostela, Campus Sur, 15782 Santiago de Compostela, Spain.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):2921-8. doi: 10.1166/jnn.2006.429.
We have recently reported preliminary data showing the efficacy of chitosan nanocapsules as carriers for oral peptide delivery. In the present work, our aim was to investigate the influence of some chitosan properties, such as the molecular weight and type of salt, on the interaction of these nanocapsules with the Caco-2 cells and also on their in vivo effectiveness. Chitosan nanocapsules were prepared by the solvent displacement technique using high (450 kDa) and medium (160 kDa) molecular weight chitosan glutamate as well as high molecular weight chitosan hydrochloride (270 kDa). The results indicated that the size of the nanocapsules was dependent on the chitosan molecular weight, whereas the zeta potential and the association efficiency of salmon calcitonin were not affected by the chitosan properties. Upon incubation with the Caco-2 cells, chitosan nanocapsules exhibited a dose-dependent cellular viability, which was hardly affected by, either the chitosan molecular weight or, the type of salt. In addition, it was observed that the transepithelial electrical resistance of the Caco-2 monolayer was not significantly modified upon their exposure to chitosan nanocapsules. The results of the in vivo studies, following oral administration to rats, indicated that chitosan nanocapsules were able to reduce significantly the serum calcium levels, and to prolong this reduction for at least 24 hours, irrespective of the type of chitosan salt and molecular weight of chitosan. Consequently, the performance of chitosan nanocapsules as oral carriers for salmon calcitonin was not affected by the characteristics of chitosan.
我们最近报告了初步数据，显示壳聚糖纳米胶囊作为口服肽递送载体的功效。在本研究中，我们的目的是研究壳聚糖的一些性质，如分子量和盐的类型，对这些纳米胶囊与Caco-2细胞相互作用以及它们体内有效性的影响。使用高（450 kDa）和中（160 kDa）分子量的壳聚糖谷氨酸盐以及高分子量的壳聚糖盐酸盐（270 kDa），通过溶剂置换技术制备壳聚糖纳米胶囊。结果表明，纳米胶囊的尺寸取决于壳聚糖的分子量，而鲑鱼降钙素的zeta电位和结合效率不受壳聚糖性质的影响。与Caco-2细胞孵育后，壳聚糖纳米胶囊表现出剂量依赖性的细胞活力，这几乎不受壳聚糖分子量或盐类型的影响。此外，观察到Caco-2单层的跨上皮电阻在暴露于壳聚糖纳米胶囊后没有显著改变。对大鼠口服给药后的体内研究结果表明，壳聚糖纳米胶囊能够显著降低血清钙水平，并将这种降低至少延长24小时，而与壳聚糖盐的类型和壳聚糖的分子量无关。因此，壳聚糖纳米胶囊作为鲑鱼降钙素口服载体的性能不受壳聚糖特性的影响。
