Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
Biomaterials. 2010 Sep;31(26):6849-58. doi: 10.1016/j.biomaterials.2010.05.042. Epub 2010 Jun 17.
In this study, we report the biodistribution of aspart-insulin, a rapid-acting insulin analogue, following oral or subcutaneous (SC) administration to rats using the single-photon emission computed tomography (SPECT)/computed tomography (CT). Oral delivery of aspart-insulin was achieved using a pH-responsive nanoparticle (NP) system composed of chitosan (CS) and poly(gamma-glutamic acid). The results obtained in the SPECT/CT study indicate that the orally administered aspart-insulin was absorbed into the systemic circulation, while the drug carrier (CS) was mainly retained in the gastrointestinal tract.Via the SC route, the peak aspart-insulin concentration in the peripheral tissue/plasma was observed at 20 min after injection. Within 3 h, half of the initial dose (ID) of aspart-insulin was degraded and excreted into the urinary bladder. In contrast, via oral delivery, there was constantly circulating aspart-insulin in the peripheral tissue/plasma during the course of the study, while 20% of the ID of aspart-insulin was metabolized and excreted into the urinary bladder. In the pharmacodynamic (PD) and pharmacokinetic (PK) evaluation in a diabetic rat model, the orally administered aspart-insulin loaded NPs produced a slower hypoglycemic response for a prolonged period of time, whereas the SC injection of aspart-insulin produced a more pronounced hypoglycemic effect for a relatively shorter duration. Finally, comparison of the PD/PK profiles of the orally administered aspart-insulin with those of the SC injection of NPH-insulin, an intermediate-acting insulin preparation, suggests the suitability of our NP system to be used as a non-invasive alternative for the basal insulin therapy.
在这项研究中，我们报告了使用单光子发射计算机断层扫描（SPECT）/计算机断层扫描（CT），经口服或皮下（SC）给予大鼠后，速效胰岛素类似物门冬胰岛素的生物分布。使用由壳聚糖（CS）和聚（γ-谷氨酸）组成的 pH 响应纳米颗粒（NP）系统实现门冬胰岛素的口服给药。SPECT/CT 研究的结果表明，口服给予的门冬胰岛素被吸收到体循环中，而药物载体（CS）主要保留在胃肠道中。通过 SC 途径，在注射后 20 分钟观察到外周组织/血浆中的门冬胰岛素达到峰值浓度。在 3 小时内，初始剂量（ID）的一半门冬胰岛素被降解并排泄到膀胱中。相比之下，通过口服给药，在研究过程中，外周组织/血浆中始终有循环的门冬胰岛素，而 ID 的 20%的门冬胰岛素被代谢并排泄到膀胱中。在糖尿病大鼠模型中的药效学（PD）和药代动力学（PK）评价中，口服给予载有门冬胰岛素的 NPs 产生了更缓慢但持续时间更长的降血糖反应，而 SC 注射门冬胰岛素则产生了更明显但持续时间相对较短的降血糖作用。最后，将口服给予的门冬胰岛素与中效胰岛素制剂 NPH-insulin 的 SC 注射的 PD/PK 曲线进行比较，表明我们的 NP 系统适合用作非侵入性的基础胰岛素治疗替代方案。
