Patil Nilam H, Devarajan Padma V
a Department of Pharmaceutical Science and Technology , Institute of Chemical Technology , Mumbai , Maharashtra , India.
Drug Deliv. 2016;23(2):429-36. doi: 10.3109/10717544.2014.916769. Epub 2014 Jun 5.
Alginic acid nanoparticles (NPs) containing insulin, with nicotinamide as permeation enhancer were developed for sublingual delivery. The lower concentration of proteolytic enzymes, lower thickness and enhanced retention due to bioadhesive property, were relied on for enhanced insulin absorption. Insulin-loaded NPs were prepared by mild and aqueous based nanoprecipitation process. NPs were negatively charged and had a mean size of ∼200 nm with low dispersity index. Insulin loading capacities of >95% suggested a high association of insulin with alginic acid. Fourier Transform Infra-Red Spectroscopy (FTIR) spectra and DSC (Differential Scanning Calorimetry) thermogram of insulin-loaded NPs revealed the association of insulin with alginic acid. Circular dichroism (CD) spectra confirmed conformational stability, while HPLC analysis confirmed chemical stability of insulin in the NPs. Sublingually delivered NPs with nicotinamide exhibited high pharmacological availability (>100%) and bioavailability (>80%) at a dose of 5 IU/kg. The high absolute pharmacological availability of 20.2% and bioavailability of 24.1% in comparison with subcutaneous injection at 1 IU/kg, in the streptozotocin-induced diabetic rat model, suggest the insulin-loaded alginic acid NPs as a promising sublingual delivery system of insulin.
开发了含有胰岛素的海藻酸纳米颗粒（NPs），并以烟酰胺作为渗透促进剂用于舌下给药。由于生物粘附特性，蛋白水解酶浓度较低、厚度较小且滞留增强，这些因素有助于增强胰岛素的吸收。通过温和的水相纳米沉淀法制备了载胰岛素纳米颗粒。纳米颗粒带负电荷，平均粒径约为200nm，分散指数较低。胰岛素负载量>95%表明胰岛素与海藻酸有高度结合。载胰岛素纳米颗粒的傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）热谱图显示了胰岛素与海藻酸的结合。圆二色性（CD）光谱证实了构象稳定性，而高效液相色谱（HPLC）分析证实了纳米颗粒中胰岛素的化学稳定性。在链脲佐菌素诱导的糖尿病大鼠模型中，以5IU/kg的剂量舌下给药含烟酰胺的纳米颗粒表现出高药理利用率（>100%）和生物利用度（>80%）。与1IU/kg皮下注射相比，载胰岛素海藻酸纳米颗粒的绝对药理利用率高达20.2%，生物利用度高达24.1%，这表明其作为一种有前景的胰岛素舌下给药系统。
