Tenci Marika, Rossi Silvia, Giannino Valentina, Vigani Barbara, Sandri Giuseppina, Bonferoni Maria Cristina, Daglia Maria, Longo Luigi Maria, Macelloni Cristina, Ferrari Franca
Department of Drug Sciences, University of Pavia, V.le Taramelli, 12, 27100 Pavia, Italy.
Cosmo SpA; Via C. Colombo 1, 20020 Lainate (MI), Italy.
Pharmaceutics. 2019 Nov 14;11(11):611. doi: 10.3390/pharmaceutics11110611.
The aim of the present work was the development of an innovative in situ gelling system, to be applied on the mucosa of the distal colon via rectal route. The system consisted of three polymers having different functions: gellan (GG), able to jellify in presence of ions; methylcellulose (MC), a thermosensitive polymer with a gelation temperature close to 50 °C; and hydroxypropylcellulose (HPC), a mucoadhesive polymer. The three polymers were able to act synergistically, increasing the permanence of the vehicle on the mucosa and forming a protective gel layer. A DoE approach, "simplex centroid mixture design," was used to identify the optimal quantitative composition of the vehicle. The response variables considered were: vehicle viscosity at room temperature; increase in vehicle viscosity on increasing temperature (from room to physiological value) and upon dilution with simulated colonic fluid (SCF); and viscoelastic behavior, thixotropic area, and mucoadhesion properties of the gel formed at 37 °C upon dilution in SCF. The optimized vehicle was loaded with maqui berry extract (MBE), known for its antioxidant and anti-inflammatory properties. MBE loading (0.5% /) into the vehicle improved rheological and mucoadhesive properties of the formulation. Both MBE and the optimized vehicle were not cytotoxic towards human fibroblasts and Caco-2 cells. Moreover, the optimized vehicle did not affect MBE antioxidant properties.
本研究的目的是开发一种创新的原位凝胶系统,通过直肠途径应用于结肠远端黏膜。该系统由三种具有不同功能的聚合物组成:结冷胶(GG),在离子存在下能够胶凝;甲基纤维素(MC),一种凝胶化温度接近50°C的热敏聚合物;以及羟丙基纤维素(HPC),一种黏膜黏附聚合物。这三种聚合物能够协同作用,增加载体在黏膜上的滞留时间并形成一层保护性凝胶层。采用了一种实验设计方法,即“单纯形重心混合物设计”,来确定载体的最佳定量组成。所考虑的响应变量包括:室温下载体的粘度;温度升高(从室温到生理值)以及用模拟结肠液(SCF)稀释时载体粘度的增加;以及在37°C下用SCF稀释后形成的凝胶的粘弹性行为、触变面积和黏膜黏附特性。优化后的载体负载了含有抗氧化和抗炎特性的马基莓提取物(MBE)。将MBE以0.5%(/)的比例负载到载体中改善了制剂的流变学和黏膜黏附特性。MBE和优化后的载体对人成纤维细胞和Caco-2细胞均无细胞毒性。此外,优化后的载体不影响MBE的抗氧化性能。