a Centro de Ciências Médicas e Farmacêuticas , Universidade Estadual do Oeste do Paraná , Cascavel/PR , Brazil.
b i3S, Instituto de Investigação em Saúde , Universidade do Porto , Porto , Portugal.
Expert Opin Drug Deliv. 2018 Mar;15(3):213-222. doi: 10.1080/17425247.2018.1420050. Epub 2017 Dec 27.
The oral route is widely accepted as the most physiological path for exogenous administration of insulin, as it closely mimic the endogenous insulin pathway. Thus, in this work it is proposed an innovative lipid-polymeric nanocarrier to delivery insulin orally. Areas covered: Nanoparticles were produced through a modified solvent emulsification-evaporation method, using ethyl palmitate and hydroxypropylmethylcellulose acetate succinate as matrix. Lipid-polymeric nanoparticles were around 300 nm in size, negatively charged (-20 mV) and associated insulin with efficiency higher than 80%. Differential scanning calorimetry suggested thermal stability of nanoparticles. In vitro release assays under simulated gastrointestinal conditions resulted in 9% and 14% of insulin released at pH 1.2 during 2 h and at pH 6.8 for 6 h, respectively, demonstrating the ability of those nanoparticles to protect insulin against premature degradation. Importantly, nanoparticles were observed to be safe at potential therapeutic concentrations as did not originate cytotoxicity to intestinal epithelial cells. Lastly, the permeability of nanoencapsulated insulin through Caco-2 monolayers and a triple Caco-2/HT29-MTX/Raji B cell model correlated well with slow release kinetics, and fosters the effectiveness of nanoparticles to promote intestinal absorption of peptidic drugs. Expert opinion: Lipid-polymeric nanoparticles were developed to encapsulate and carry insulin through intestine. Overall, nanoparticles provide insulin stability and intestinal permeability.
口服途径被广泛认为是外源性给予胰岛素的最生理途径，因为它非常类似于内源性胰岛素途径。因此，在这项工作中，提出了一种创新的脂质-聚合物纳米载体来口服递送胰岛素。 涵盖领域：通过改良的溶剂乳化-蒸发法生产纳米粒子，使用棕榈酸乙酯和羟丙基甲基纤维素醋酸琥珀酸酯作为基质。脂质-聚合物纳米粒子的大小约为 300nm，带负电荷（-20mV），与胰岛素的结合效率高于 80%。差示扫描量热法表明纳米粒子具有热稳定性。在模拟胃肠道条件下的体外释放试验中，在 pH 1.2 下 2 小时和 pH 6.8 下 6 小时分别释放了 9%和 14%的胰岛素，表明这些纳米粒子能够保护胰岛素免受过早降解。重要的是，纳米粒子在潜在的治疗浓度下被观察是安全的，因为它们不会引起肠上皮细胞的细胞毒性。最后，纳米封装胰岛素通过 Caco-2 单层和三重 Caco-2/HT29-MTX/Raji B 细胞模型的渗透性与缓慢释放动力学密切相关，这促进了纳米粒子促进肽类药物肠道吸收的有效性。专家意见：脂质-聚合物纳米粒子的开发是为了包裹和携带胰岛素通过肠道。总的来说，纳米粒子提供了胰岛素的稳定性和肠道通透性。
