Design of cationic lipid nanoparticles for ocular delivery: Development, characterization and cytotoxicity
Design of cationic lipid nanoparticles for ocular delivery: Development, characterization and cytotoxicity
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DOI：
10.1016/j.ijpharm.2013.11.025
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发表时间：
2014-01-30
影响因子：
5.8
通讯作者：
Souto, Eliana B.
中科院分区：
文献类型：
--
作者：
Fangueiro, Joana F.;Andreani, Tatiana;Souto, Eliana B.
在本研究中，我们通过完全析因设计开发了基于多重乳化技术的脂纳米粒(LN)分散体，用于亲水性药物或/和蛋白质的包埋。为了通过静电吸引增加眼内滞留时间和粘附性，在析因设计得到的最佳层粘连分散体脂基质中加入阳离子脂类，即十六烷基三甲基溴化铵(CTAB)。有有限数量的研究报道了在LN中用于药物输送的阳离子试剂的理想浓度。本文认为，在配制安全稳定的LN时，阳离子浓度的选择是至关重要的。CTAB被包含在LN的脂质基质中，测试了四种不同浓度(0.25%、0.5%、0.75%或1.0%wt)的LN，以及组成如何影响LN的物理化学参数、脂质结晶和多形性以及储存期间的分散稳定性。为了开发一种安全、兼容的眼部给药系统，将CTAB-LN分散体暴露于人视网膜母细胞瘤细胞系Y-79。CTAB-LN分散体的毒性测试是寻找开发阳离子LN的最佳CTAB浓度的基本工具，CTAB的最佳浓度为CTAB的0.5wt%。(C)2013爱思唯尔B.V.保留所有权利。
In the present study we have developed lipid nanoparticle (LN) dispersions based on a multiple emulsion technique for encapsulation of hydrophilic drugs or/and proteins by a full factorial design. In order to increase ocular retention time and mucoadhesion by electrostatic attraction, a cationic lipid, namely cetyltrimethylammonium bromide (CTAB), was added in the lipid matrix of the optimal LN dispersion obtained from the factorial design. There are a limited number of studies reporting the ideal concentration of cationic agents in LN for drug delivery. This paper suggests that the choice of the concentration of a cationic agent is critical when formulating a safe and stable LN. CTAB was included in the lipid matrix of LN, testing four different concentrations (0.25%, 0.5%, 0.75%, or 1.0%wt) and how composition affects LN behavior regarding physical and chemical parameters, lipid crystallization and polymorphism, and stability of dispersion during storage. In order to develop a safe and compatible system for ocular delivery, CTAB-LN dispersions were exposed to Human retinoblastoma cell line Y-79. The toxicity testing of the CTAB-LN dispersions was a fundamental tool to find the best CTAB concentration for development of these cationic LN, which was found to be 0.5 wt% of CTAB. (C) 2013 Elsevier B.V. All rights reserved.