Department of Chemistry, School of Sciences, University of Navarra, Irunlarrea s/n, Pamplona 31080, Navarra, Spain.
Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, Irunlarrea s/n, Pamplona 31080, Navarra, Spain.
Colloids Surf B Biointerfaces. 2018 Mar 1;163:64-72. doi: 10.1016/j.colsurfb.2017.12.038. Epub 2017 Dec 21.
This work describes the feasibility of poly(anhydride) nanoparticles as carriers for the oral administration of glibenclamide (GB) as well as the in vivo evaluation of their hypolipidemic effect in a C. elegans model. For this purpose, and in order to increase the GB payload, the drug was encapsulated in nanoparticles in presence of cyclodextrins (either βCD or HPβCD). The optimized nanoparticles displayed a size of about 220 nm and a negative zeta potential (-40 mV), with a drug loading up to 52 μg/mg. Small-angle neutron scattering studies suggested an internal fractal-like structure, based on the repetition of spherical blocks of polymeric units (about 5 nm) grouped to form the nanoparticle. X-ray diffraction study confirmed the absence of crystalline GB molecules due to its dispersion into the nanoparticles, either entrapped in the polymer chains and/or included into cyclodextrin cavities. GB-loaded nanoparticles induced a significant reduction in the fat content of C. elegans. This hypolipidemic effect was slightly higher for the nanoparticles prepared with coencapsulated HPβCD (8.2%) than for those prepared with βCD (7.9%) or in the absence of cyclodextrins (7.0%). In summary, the coencapsulation of cyclodextrins into poly(anhydride) nanoparticles could be an interesting strategy to develop new oral formulations of glibenclamide.
这项工作描述了聚（酸酐）纳米粒子作为将格列本脲（GB）口服给药的载体的可行性，以及在秀丽隐杆线虫模型中评估其降血脂作用的体内评价。为此，为了增加 GB 的载药量，在环糊精（βCD 或 HPβCD）存在的情况下将药物包封在纳米粒子中。优化后的纳米粒子的粒径约为 220nm，zeta 电位为负（-40mV），药物载药量高达 52μg/mg。小角中子散射研究表明，基于聚合物单元（约 5nm）的球形块的重复，形成了具有内部分形样结构的纳米粒子。X 射线衍射研究证实由于其分散在纳米粒子中，不存在结晶 GB 分子，无论是包埋在聚合物链中还是包含在环糊精腔中。载有 GB 的纳米粒子可显著降低秀丽隐杆线虫的脂肪含量。与用 coencapsulated HPβCD（8.2%）制备的纳米粒子相比，用 βCD（7.9%）或不使用环糊精（7.0%）制备的纳米粒子的降血脂效果略高。总之，将环糊精 coencapsulated 到聚（酸酐）纳米粒子中可能是开发格列本脲新口服制剂的一种有趣策略。
