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载有司他夫定的纳米结构脂质载体(NLC)体外差异蛋白吸附模式评价及其对脑部潜在靶向性。

Evaluation of the in vitro differential protein adsorption patterns of didanosine-loaded nanostructured lipid carriers (NLCs) for potential targeting to the brain.

机构信息

Department of Pharmaceutics, Biopharmaceutics, NutriCosmetics, Freie Universität Berlin, Berlin, Germany.

出版信息

J Liposome Res. 2011 Sep;21(3):245-54. doi: 10.3109/08982104.2010.539186. Epub 2010 Dec 21.

DOI:10.3109/08982104.2010.539186
PMID:21174528
Abstract

The preferential in vitro adsorption of apolipoprotein E (Apo E) onto the surface of colloidal drug carriers may be used as a strategy to evaluate the in vivo potential for such systems to transport drugs to the brain. The aim of this research was to investigate the in vitro protein adsorption patterns of didanosine-loaded nanostructured lipid carriers (DDI-NLCs), using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), in order to establish the potential for NLCs to deliver DDI to the brain. NLC formulations were manufactured using high-pressure homogenization using a lipid matrix consisting of a mixture of Precirol(®) ATO 5 and Transcutol(®) HP. The 2-D PAGE analysis revealed that NLCs in formulations stabilized using Solutol(®) HS 15 alone or with a ternary surfactant system consisting of Solutol(®) HS 15, Tween(®) 80, and Lutrol(®) F68, preferentially adsorbed proteins, such as Apo E. Particles stabilized with Tween(®) 80 and Lutrol(®) F68 did not adsorb Apo E in these studies, which could be related to the relatively large particle size and hence small surface area observed for these NLCs. These findings have revealed that DDI-loaded NLCs may have the potential to deliver DDI to the brain in vivo and, in addition, to Tween(®) 80, which has already been shown to have the ability to facilitate the targeting of colloidal drug delivery systems to the brain. Solutol(®) HS 15-stabilized nanoparticles may also achieve a similar purpose.

摘要

优先将载脂蛋白 E(Apo E)吸附到胶体药物载体的表面上,这可能被用作评估此类系统向大脑输送药物的体内潜力的策略。本研究旨在使用二维聚丙烯酰胺凝胶电泳(2-D PAGE)研究载有叠氮胸苷的纳米结构脂质载体(DDI-NLC)的体外蛋白吸附模式,以确定 NLC 将 DDI 递送到大脑的潜力。使用高压匀质法制造 NLC 制剂,使用由 Precirol(®)ATO 5 和 Transcutol(®)HP 混合物组成的脂质基质。2-D PAGE 分析表明,单独使用 Solutol(®)HS 15 或使用由 Solutol(®)HS 15、吐温(®)80 和 Lutrol(®)F68 组成的三元表面活性剂系统稳定的 NLC 制剂,优先吸附蛋白质,如 Apo E。在这些研究中,用吐温(®)80 和 Lutrol(®)F68 稳定的颗粒不吸附 Apo E,这可能与观察到的这些 NLC 相对较大的粒径和因此较小的表面积有关。这些发现表明,载有 DDI 的 NLC 可能具有将 DDI 递送到体内大脑的潜力,此外,载有 DDI 的 NLC 还具有已显示出能够促进胶体药物传递系统靶向大脑的能力的吐温(®)80。Solutol(®)HS 15 稳定的纳米颗粒也可能达到类似的目的。

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