Page-Clisson M E, Pinto-Alphandary H, Ourevitch M, Andremont A, Couvreur P
Laboratoire de Pharmacie Galénique et Biopharmacie, URA CNRS 1218, Université Paris XI, 92296, Châtenay-Malabry Cedex, France.
J Control Release. 1998 Dec 4;56(1-3):23-32. doi: 10.1016/s0168-3659(98)00065-0.
This paper describes the optimization of the preparation of ciprofloxacin-loaded polyethylbutylcyanoacrylate (PEBCA) nanoparticles. The association of ciprofloxacin with nanoparticles was performed by emulsion polymerization, but successful entrapment was only obtained in the presence of acetone in the polymerization medium. This preparation process led to a stable ciprofloxacin nanoparticle suspension, with a mean size value twice as high as that obtained in the absence of drug, and an association efficiency of 82%. Moreover, the molecular weight value of ciprofloxacin nanoparticles was shown to be reduced as compared with unloaded nanoparticles. Drug release from the colloidal carrier in medium containing esterase was found to be very slow (a maximum of 51.5% after 48 h), suggesting that this release resulted from bioerosion of the polymer matrix. Interestingly, it was observed that 30.5% of the initial amount of ciprofloxacin was not detectable by HPLC analysis after nanoparticle preparation and corresponded either to ciprofloxacin covalently bound to PEBCA or to ciprofloxacin chemically degraded during the polymerization process. 19F-NMR analysis demonstrated that ciprofloxacin entrapped into nanoparticles was only in its neutral form. The measurements of molecular weight suggest the participation of the antibiotic as an anionic polymerization initiator, leading to the formation of a chemical bond between some of the drug and the polymer. These data allowed us to propose a model describing the association of ciprofloxacin with PEBCA nanoparticles obtained by emulsion polymerization.
本文描述了载环丙沙星聚乙基丁基氰基丙烯酸酯（PEBCA）纳米颗粒制备工艺的优化。环丙沙星与纳米颗粒的结合通过乳液聚合进行，但只有在聚合介质中存在丙酮时才能成功包封。该制备过程得到了稳定的环丙沙星纳米颗粒悬浮液，其平均粒径值是未加药物时的两倍，包封效率为82%。此外，与未载药的纳米颗粒相比，环丙沙星纳米颗粒的分子量值有所降低。发现在含有酯酶的介质中，胶体载体的药物释放非常缓慢（48小时后最大释放量为51.5%），这表明这种释放是由聚合物基质的生物侵蚀引起的。有趣的是，观察到纳米颗粒制备后，通过HPLC分析检测不到30.5%的初始环丙沙星量，这部分环丙沙星要么与PEBCA共价结合，要么在聚合过程中发生化学降解。19F-NMR分析表明，包封在纳米颗粒中的环丙沙星仅呈中性形式。分子量的测量表明抗生素作为阴离子聚合引发剂参与其中，导致部分药物与聚合物之间形成化学键。这些数据使我们能够提出一个模型，描述通过乳液聚合获得的环丙沙星与PEBCA纳米颗粒的结合。
