Leroueil-Le Verger M, Fluckiger L, Kim Y I, Hoffman M, Maincent P
Université Henri Poincaré, Nancy Cedex, France.
Eur J Pharm Biopharm. 1998 Sep;46(2):137-43. doi: 10.1016/s0939-6411(98)00015-0.
Isradipine, an antihypertensive agent, was encapsulated by the nanoprecipitation method using polymers including poly(epsilon-caprolactone), poly(D,L-lactide) and poly(d, L-lactide-co-glycolide). In vitro scanning electron microscopy and differential scanning calorimetry were used to characterize the nanoparticles. The average diameters of the nanoparticles ranged from 110 nm to 208 nm. PCL nanoparticles were larger than nanoparticles prepared with the other polymers. The zeta potential of the nanoparticles was negative, with values of about -25 mV which promoted good stabilization of the particles. The amorphous state of PLA and PLAGA non-loaded nanoparticles and the semi-crystalline state of PCL were demonstrated with X-ray diffraction and differential scanning calorimetry. For all nanoparticles, isradipine was found to be totally amorphous in the polymer which suggested that the drug was molecularly dispersed in the matrix. The colloidal suspensions displayed a sustained release profile in comparison with the drug release profile of isradipine in a PEG solution. Results from this investigation suggest that these nanospheres will be a good candidate delivery system for oral administration, to reduce the initial hypotensive peak and to prolong the antihypertensive effect of the drug.
伊拉地平是一种抗高血压药物，采用包括聚（ε-己内酯）、聚（D，L-丙交酯）和聚（D，L-丙交酯-共-乙交酯）在内的聚合物通过纳米沉淀法进行包封。使用体外扫描电子显微镜和差示扫描量热法对纳米颗粒进行表征。纳米颗粒的平均直径范围为110纳米至208纳米。聚己内酯纳米颗粒比用其他聚合物制备的纳米颗粒更大。纳米颗粒的ζ电位为负，约为 -25 mV，这促进了颗粒的良好稳定性。通过X射线衍射和差示扫描量热法证明了聚乳酸和聚乳酸-羟基乙酸共聚物未负载纳米颗粒的无定形状态以及聚己内酯的半结晶状态。对于所有纳米颗粒，发现伊拉地平在聚合物中完全呈无定形，这表明药物在基质中呈分子分散状态。与伊拉地平在聚乙二醇溶液中的药物释放曲线相比，胶体悬浮液呈现出缓释曲线。这项研究的结果表明，这些纳米球将是口服给药的良好候选递送系统，以降低初始降压峰值并延长药物的降压效果。
