Laboratory of Pharmaceutical Engineering, Aichi Gakuin University, Nagoya, Japan.
Eur J Pharm Biopharm. 2011 Jan;77(1):84-8. doi: 10.1016/j.ejpb.2010.11.002. Epub 2010 Nov 11.
In this study, we investigated surface-modified nanoparticles (NP) formulated using a biodegradable polymer, poly(D,L-lactide-co-glycolide) (PLGA), for targeting central nervous system (CNS) diseases. Polysorbate 80 (P80), poloxamer 188 (P188), and chitosan (CS) were used to modify the surfaces of PLGA NP to improve the brain delivery of NP. Surface-modified PLGA NP were formulated using an emulsion solvent diffusion method. 6-Coumarin was used as a fluorescent label for NP. The different formulations of 6-coumarin-loaded PLGA NP were injected into rats via carotid arteries. NP remaining in the brain were evaluated quantitatively, and brain slices were observed using confocal laser scanning microscopy (CLSM). Carotid artery administration was more effective for delivering NP into the brain compared to intravenous administration. After administration, NP concentrations in the brain were increased by NP surface modification, especially CS- and P80-PLGA NP. CLSM observations indicated that P80-PLGA NP could cross the blood-brain barrier and thus serve as a drug delivery system for the CNS. These results indicate that surface-modified PLGA NP have a high potential for use in CNS delivery systems.
在这项研究中，我们研究了使用可生物降解聚合物聚（D，L-丙交酯-共-乙交酯）（PLGA）制备的表面修饰纳米颗粒（NP），用于靶向中枢神经系统（CNS）疾病。聚山梨酯 80（P80）、泊洛沙姆 188（P188）和壳聚糖（CS）用于修饰 PLGA NP 的表面，以提高 NP 的脑内传递。使用乳化溶剂扩散法制备表面修饰的 PLGA NP。6-香豆素被用作 NP 的荧光标记。将不同配方的载有 6-香豆素的 PLGA NP 通过颈动脉注入大鼠体内。通过定量评估留在大脑中的 NP，并使用共聚焦激光扫描显微镜（CLSM）观察脑切片。与静脉注射相比，颈动脉给药更有利于将 NP 递送到大脑中。给药后，通过 NP 表面修饰，尤其是 CS 和 P80-PLGA NP，增加了 NP 在大脑中的浓度。CLSM 观察表明，P80-PLGA NP 可以穿过血脑屏障，因此可以作为 CNS 的药物递送系统。这些结果表明，表面修饰的 PLGA NP 具有在 CNS 递药系统中应用的巨大潜力。
