Abstract：
The detachable dissolving microneedles (DDMNs) feature an array of needles capable of being separated from the base sheet during administration. Here they were fabricated to address delivery efficiency and storage stability of insulin. The constructed insulin-DDMN is multi-layered, with 1) a hard tip cover layer; 2) a layer of regular short-acting insulin (RI) mixed with hyaluronic acid (HA) and sorbitol (Sor) which occupies the taper tip region of the needles; 3) a barrier layer situated above the RI layer; and 4) a fast-dissolving layer connecting the barrier layer to the base sheet. RI entrapped in DDMNs exhibited enhanced thermal stability; it could be stored at 40 °C for 35 days without losing significant biological activity. Differential scanning calorimetric analysis revealed that the HA-Sor matrix could improve the denaturation temperature of the RI from lower than room temperature to 186 °C. Tests in ex vivo porcine skin demonstrated RI delivery efficiency of 91±1.59 %. Experiments with diabetic rats revealed sustained release of RI, i.e., when compared to subcutaneous injection with the same RI dose, RI-DDMNs produced slower absorption of insulin into blood circulation, delayed onset of hypoglycemic effect, longer serum insulin half-life, and longer hypoglycemic duration.
摘要：
可拆卸的溶解微针(DDMN)的特征在于能够在施用期间与基片分离的针阵列。在这里,它们被制造以解决胰岛素的递送效率和储存稳定性。构建的胰岛素-DDMN是多层的，1)硬尖端覆盖层;2)与透明质酸(HA)和山梨糖醇(Sor)混合的常规短效胰岛素(RI)层,其占据针的锥形尖端区域;3)位于RI层上方的屏障层;和4)将屏障层连接至基片的快速溶解层。包埋在DDMN中的RI表现出增强的热稳定性；它可以在40°C下储存35天，而不会失去明显的生物活性。差示扫描量热分析表明，HA-Sor基质可以将RI的变性温度从低于室温提高到186°C。离体猪皮肤中的测试表明RI递送效率为91±1.59%。对糖尿病大鼠的实验显示RI的持续释放，即，与相同RI剂量的皮下注射相比，RI-DDMNs使胰岛素吸收到血液循环中较慢，降血糖作用的延迟发作，更长的血清胰岛素半衰期，和更长的低血糖持续时间。
