School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
Bioconjug Chem. 2010 Oct 20;21(10):1720-3. doi: 10.1021/bc100093v.
A new oral delivery system for insulin was developed aiming to improve bioavailability based on a conjugate between insulin and low molecular weight chitosan (LMWC) of narrow molecular weight distribution. The conjugate was synthesized from the reaction between site-specifically modified insulin at the lysine residue of the B-chain and sulfhydryl-modified LMWC. To investigate the effect of MWs of LMWC on oral bioavailability of insulin, various LMWCs (3, 6, 9, and 13k average MW) with narrow MW distribution were used to synthesize LMWC-insulin conjugates. The content of insulin in the LMWC-insulin conjugates was calculated by UV spectrophotometer: 62%, 44%, 38%, and 29% for 3, 6, 9, and 13 kDa LMWC, respectively. The biological activity of insulin in LMWC(6k)-insulin conjugate in vivo was 43 ± 0.7%. LMWC-insulin conjugates after oral administration to diabetic rat models could control blood glucose levels effectively for several hours. Of those conjugates, LMWC(9k)-insulin exhibited the highest pharmacodynamic bioavailability of 3.7 ± 0.3% relative to that of subcutaneously (s.c.) injected insulin (100%).
研究人员开发了一种新的胰岛素口服递送系统，旨在通过胰岛素与低分子量壳聚糖（LMWC）的缀合物来提高生物利用度，该缀合物是通过 B 链赖氨酸残基上的胰岛素与巯基修饰的 LMWC 的特异性反应合成的。为了研究 LMWC 的分子量对胰岛素口服生物利用度的影响，使用了具有窄分子量分布的各种 LMWC（3、6、9 和 13k 平均分子量）来合成 LMWC-胰岛素缀合物。通过紫外分光光度计计算 LMWC-胰岛素缀合物中胰岛素的含量：对于 3、6、9 和 13 kDa 的 LMWC，分别为 62%、44%、38%和 29%。LMWC（6k）-胰岛素缀合物在体内的胰岛素生物活性为 43±0.7%。口服给予糖尿病大鼠模型后，LMWC-胰岛素缀合物能够有效控制血糖水平数小时。在这些缀合物中，LMWC（9k）-胰岛素的药效学生物利用度最高，相对皮下（sc）注射胰岛素（100%）为 3.7±0.3%。
