University Institute of Pharmaceutical Sciences (UGC Center of Advanced Studies), Panjab University, Chandigarh, India.
J Pharm Pharmacol. 2011 Mar;63(3):342-51. doi: 10.1111/j.2042-7158.2010.01225.x.
This study aims at formulating solid lipid nanoparticles (SLNs) of quercetin, a natural flavonoid with established antioxidant activity, for intravenous administration in order to improve its permeation across the blood-brain barrier into the CNS, and eventually to improve the therapeutic efficacy of this molecule in Alzheimer's disease.
The SLNs of quercetin were formulated using Compritol as the lipid and Tween 80 as the surfactant through a microemulsification technique, and optimized employing a 3(2) central composite design (CCD). Selection of the optimized SLN formulation, using brute-force methodology and overlay plots, was based on its efficiency of entrapping quercetin inside the lipophilic core, particle size, surface charge potential and ability of the SLNs to release the entrapped drug completely. The optimized formulation was subjected to various in-vivo behavioral and biochemical studies in Wistar rats.
The optimized formulation exhibited a particle size of less than 200 nm, 85.73% drug entrapment efficiency and a zeta potential of 21.05 mV. In all the in-vivo behavioral and biochemical experiments, the rats treated with SLN-encapsulated quercetin showed markedly better memory-retention vis-à-vis test and pure quercetin-treated rats.
The studies demonstrated successful targeting of the potent natural antioxidant, quercetin, to brain as a novel strategy having significant therapeutic potential to treat Alzheimer's disease.
本研究旨在将槲皮素（一种具有抗氧化活性的天然类黄酮）制成固体脂质纳米粒（SLN），用于静脉给药，以提高其穿过血脑屏障进入中枢神经系统的通透性，最终提高该分子在阿尔茨海默病中的治疗效果。
采用微乳化技术，以 Compritol 为脂质，Tween 80 为表面活性剂，制备槲皮素 SLN，并通过 3(2)中心组合设计（CCD）进行优化。采用暴力法和叠加图，根据优化的 SLN 制剂对槲皮素的包封效率、粒径、表面电荷势和完全释放包封药物的能力，选择最佳的 SLN 制剂。对优化后的制剂进行了 Wistar 大鼠的各种体内行为和生化研究。
优化后的制剂粒径小于 200nm，药物包封效率为 85.73%，zeta 电位为 21.05mV。在所有体内行为和生化实验中，与单纯给予槲皮素治疗的大鼠相比，给予 SLN 包封的槲皮素治疗的大鼠的记忆保留明显更好。
研究表明，将强效天然抗氧化剂槲皮素靶向递送至大脑是一种具有显著治疗阿尔茨海默病潜力的新策略。
