Department of Physical Chemistry, Faculty of Pharmacy, Institute of Nanoscience and Nanotechnology, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
Colloids Surf B Biointerfaces. 2010 Dec 1;81(2):412-21. doi: 10.1016/j.colsurfb.2010.07.029. Epub 2010 Jul 27.
Packaging small drug molecules, such as non-steroidal anti-inflammatory drugs (NSAIDs) into nanoparticulate systems has been reported as a promising approach to improve the drug's bioavailability, biocompatibility and safety profiles. In the last 20 years, lipid nanoparticles (lipid dispersions) entered the nanoparticulate library as novel carrier systems due to their great potential as an alternative to other systems such as polymeric nanoparticles and liposomes for several administration routes. For ocular instillation nanoparticulate carriers are required to have a low mean particle size, with the lowest polydispersity as possible. The purpose of this work was to study the combined influence of 2-level, 4-factor variables on the formulation of flurbiprofen (FB), a lipophilic NSAID, in lipid carriers currently named as nanostructured lipid carriers (NLC). NLC were produced with stearic acid (SA) and castor oil (CO) stabilized by Tween® 80 (non-ionic surfactant) in aqueous dispersion. A 2(4) full factorial design based on 4 independent variables was used to plan the experiments, namely, the percentage of SA with regard to the total lipid, the FB concentration, the stabilizer concentration, and the storage conditions (i.e., storage temperature). The effects of these parameters on the mean particle size, polydispersity index (PI) and zeta potential (ZP) were investigated as dependent variables. The optimization process was achieved and the best formulation corresponded to the NLC formulation composed of 0.05 (wt%) FB, 1.6 (wt%) Tween® 80 and a 50:50 ratio of SA to CO, with an average diameter of 288 nm, PI 0.245 of and ZP of -29 mV. This factorial design study has proven to be a useful tool in optimizing FB-loaded NLC formulations. Stability of the optimized NLC was predicted using a TurbiScanLab® and the ocular tolerance was assessed in vitro and in vivo by the Eytex® and Draize test, respectively. The developed systems were shown physico-chemically stable with high tolerance for eye instillation.
将小药物分子（如非甾体抗炎药（NSAIDs））包装到纳米颗粒系统中已被报道为一种提高药物生物利用度、生物相容性和安全性的有前途的方法。在过去的 20 年中，由于脂质纳米粒（脂质分散体）作为替代其他系统（如聚合物纳米粒和脂质体）的载体系统具有很大的潜力，因此进入了纳米颗粒库，可用于多种给药途径。对于眼部滴注，纳米颗粒载体需要具有低平均粒径和尽可能低的多分散性。本工作旨在研究 2 水平、4 因素变量对亲脂性 NSAID 氟比洛芬（FB）在目前称为纳米结构化脂质载体（NLC）的脂质载体中的配方的综合影响。NLC 是由硬脂酸（SA）和蓖麻油（CO）在水性分散体中用 Tween®80（非离子表面活性剂）稳定制成的。使用基于 4 个独立变量的 2(4)完全因子设计来规划实验，即 SA 与总脂质的百分比、FB 浓度、稳定剂浓度和储存条件（即储存温度）。将这些参数对平均粒径、多分散指数（PI）和 Zeta 电位（ZP）的影响作为因变量进行了研究。优化过程完成后，最佳配方对应于由 0.05（wt%）FB、1.6（wt%）Tween®80 和 SA 与 CO 的 50:50 比例组成的 NLC 配方，平均粒径为 288nm、PI 为 0.245 和 ZP 为-29mV。这项因子设计研究已被证明是优化 FB 负载 NLC 配方的有用工具。使用 TurbiScanLab®预测了优化的 NLC 的稳定性，并分别通过 Eytex®和 Draize 试验评估了体外和体内的眼部耐受性。开发的系统在物理化学上表现出稳定性，对眼部滴注具有高耐受性。
