Fresta M, Cavallaro G, Giammona G, Wehrli E, Puglisi G
Istituto di Chimica Farmaceutica e Tossicologica, Università di Catania, Italy.
Biomaterials. 1996 Apr;17(8):751-8. doi: 10.1016/0142-9612(96)81411-6.
Biocompatible and biodegradable colloidal drug delivery systems can be obtained by means of in situ polymerization of alkylcyanoacrylate. In particular, nanocapsules of polyethylcyanoacrylate (PECA) were prepared by adding the monomer to an organic phase, consisting of Miglyol 812 and an organic solvent (ethanol, acetone or acetonitrile), and subsequently mixing the organic phase with an aqueous phase containing Pluronic F68 at different concentrations. The possible mechanism of formation and the influence of preparation conditions on the quality of nanocapsule formulations were investigated by freeze-fracture electron microscopy and laser light scattering using both the inverse Laplace transform and the standard cumulant analysis for data fitting. High-quality nanocapsule systems were obtained using an aprotic fully water-miscible organic solvent such as acetone. The presence of ethanol led to the formation of both nanospheres and nanocapsules. The concentrations of nonionic surfactant in the aqueous phase of monomer in the organic phase did not influence the kind of colloidal suspension obtained. The oil simply plays the role of monomer support. The diameter of PECA nanoparticles (nanospheres and nanocapsules) ranged from 100 to 400 nm. Three antiepileptic drugs (Ethosuximide, 5,5-diphenyl hydantoin and carbamazepine) were entrapped in PECA nanocapsules. The loading capacity of PECA nanocapsules, prepared using acetone as organic solvent, varied from 1% to 11% (drug/dried material) as a function of the solubility (affinity) of the different drugs with the oil core. This parameter also influenced the release from PECA nanocapsules, which was slower for drugs with a higher affinity for Miglyol 812. By encapsulating the three antiepileptic drugs in the PECA nanocapsules, it was possible to achieve controlled drug release. The mechanism of drug release from PECA nanocapsules was mainly diffusion from the oil core through the intact polymer barrier.
生物相容性和可生物降解的胶体药物递送系统可通过氰基丙烯酸烷基酯的原位聚合获得。具体而言，通过将单体添加到由Miglyol 812和有机溶剂（乙醇、丙酮或乙腈）组成的有机相中，随后将有机相与含有不同浓度泊洛沙姆F68的水相混合，制备了聚乙基氰基丙烯酸酯（PECA）纳米胶囊。通过冷冻断裂电子显微镜和激光光散射，使用逆拉普拉斯变换和标准累积量分析进行数据拟合，研究了纳米胶囊制剂的可能形成机制以及制备条件对其质量的影响。使用非质子性完全与水混溶的有机溶剂如丙酮可获得高质量的纳米胶囊系统。乙醇的存在导致形成纳米球和纳米胶囊。有机相中单体水相中非离子表面活性剂的浓度不影响所获得的胶体悬浮液的种类。油仅起单体载体的作用。PECA纳米颗粒（纳米球和纳米胶囊）的直径范围为100至400nm。三种抗癫痫药物（乙琥胺、5,5 - 二苯基乙内酰脲和卡马西平）被包裹在PECA纳米胶囊中。以丙酮为有机溶剂制备的PECA纳米胶囊的载药量随不同药物与油相核心的溶解度（亲和力）而变化，范围为1%至11%（药物/干燥材料）。该参数也影响了PECA纳米胶囊的释放，对于与Miglyol 812亲和力较高的药物，释放较慢。通过将三种抗癫痫药物包裹在PECA纳米胶囊中，可以实现药物的控释。药物从PECA纳米胶囊中释放的机制主要是从油相核心通过完整的聚合物屏障扩散。
