Gref R, Quellec P, Sanchez A, Calvo P, Dellacherie E, Alonso M J
School of Pharmacy, University of Paris Sud, UMR CNRS 8612, Châtenay Malabry, France.
Eur J Pharm Biopharm. 2001 Mar;51(2):111-8. doi: 10.1016/s0939-6411(00)00143-0.
Cyclosporin A (CyA) loaded poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) micro- and nanoparticles have been developed using an emulsion-solvent evaporation method. Physico-chemical properties, peptide loading content and in vitro release profiles of these novel CyA carriers were compared with those corresponding to conventional PLA micro- and nanoparticles. Results obtained confirm the previously described disposition of PEG chains on the surface of the PLA-PEG formulations. In addition, they revealed the presence of CyA molecules on the surface of both PLA and PLA-PEG systems. Further determination of the surface chemical composition by electron spectroscopy for chemical analysis (ESCA) allowed us to quantify the amount of CyA in the nanospheres' top layers, this amount being higher for nanoparticles than for microparticles, and higher for the PLA systems than for those based on PLA-PEG. In vitro release experiments revealed that PLA-PEG particles provided a more adequate control of CyA release than conventional PLA micro- and nanoparticles. Physico-chemical characterization of the systems during the release studies showed that the developed PLA and PLA-PEG micro- and nanoparticles were not degraded, which suggest a diffusion-mediated release mechanism. Furthermore, we have hypothesized that the hydrophilic outer shell of PEG provides a stationary layer for the diffusion of CyA.
采用乳液-溶剂蒸发法制备了负载环孢素A（CyA）的聚乳酸-聚乙二醇（PLA-PEG）微米和纳米颗粒。将这些新型CyA载体的物理化学性质、肽负载量和体外释放曲线与相应的传统PLA微米和纳米颗粒进行了比较。所得结果证实了先前所述的PEG链在PLA-PEG制剂表面的分布情况。此外，结果还显示在PLA和PLA-PEG体系的表面均存在CyA分子。通过化学分析电子能谱（ESCA）进一步测定表面化学成分，使我们能够量化纳米球顶层中CyA的含量，纳米颗粒中的该含量高于微米颗粒，且PLA体系中的含量高于基于PLA-PEG的体系。体外释放实验表明，与传统的PLA微米和纳米颗粒相比，PLA-PEG颗粒对CyA释放的控制更为理想。释放研究过程中对体系的物理化学表征表明，所制备的PLA和PLA-PEG微米和纳米颗粒未发生降解，这表明其释放机制为扩散介导。此外，我们推测PEG的亲水性外壳为CyA的扩散提供了一个固定层。
