Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
Vitreo-Retinal Department, Centro Privado de Ojos Romagosa SA Fundación VER, Deán Funes 429/432, Córdoba, Argentina.
Int J Pharm. 2020 Jan 5;573:118795. doi: 10.1016/j.ijpharm.2019.118795. Epub 2019 Nov 1.
Triamcinolone acetonide (TA) is an effective drug widely (off-label) used in the treatment of several ocular diseases involving inflammation and angiogenic processes. However, the use of TA ocular presents some limitations mainly related to its excipient composition, as in the case of benzyl alcohol. Thus, the aim of this work was to obtain an alternative TA formulation based on lipid nanocapsules (LNCs). Triamcinolone acetonide-loaded lipid nanocapsules (TA-LNCs) were obtained by the phase inversion temperature process without the use of irritating excipients, by combining lipids and surfactants generally recognized as safe. Pre-formulation studies were carried out to evaluate the TA solubility in different co-surfactants and to optimize the lipid core composition in order to enhance the drug loading and encapsulation rate in the LNCs. A stable final TA-LNC formulation was obtained with a mean particle size (MPS) of below 50 nm, a narrow size distribution (PDI < 0.2), a negative zeta potential (ZP) and a high encapsulation efficiency (%EE > 98%). In vitro cellular viability assays revealed that blank LNCs and TA-LNCs at 0.1 µg/mL did not affect the viability of the human corneal epithelial (HCE) cells. TA-LNCs showed a high anti-inflammatory activity below the toxicity level, with a reduction of 30% in interleukin (IL)-6 secretion observed in an in vitro model using the same cell line. More importantly, the TA-LNCs revealed a therapeutic efficacy in the endotoxin-induced uveitis (EIU) rabbit model with a significant attenuation of clinical signs of an inflammatory response. These findings make the TA-LNCs a safer and more efficient alternative for the treatment of eye disorders.
曲安奈德（TA）是一种有效的药物，广泛（超适应证）用于治疗涉及炎症和血管生成过程的几种眼部疾病。然而，TA 眼部用药存在一些局限性，主要与赋形剂组成有关，如苯甲醇。因此，本工作旨在获得基于脂质纳米囊（LNC）的 TA 替代制剂。通过相转变温度法，在不使用刺激性赋形剂的情况下获得载有曲安奈德的脂质纳米囊（TA-LNC），将通常被认为是安全的脂质和表面活性剂结合在一起。进行了预配方研究，以评估 TA 在不同助表面活性剂中的溶解度，并优化脂质核组成，以提高药物在 LNC 中的载药量和包封率。最终获得了一种稳定的 TA-LNC 制剂，其平均粒径（MPS）低于 50nm，粒径分布较窄（PDI<0.2），负 Zeta 电位（ZP）和高包封效率（%EE>98%）。体外细胞活力测定表明，空白 LNC 和 TA-LNC 在 0.1μg/mL 时不会影响人角膜上皮（HCE）细胞的活力。TA-LNC 在低于毒性水平下表现出高抗炎活性，在用相同细胞系建立的体外模型中观察到白细胞介素（IL）-6 分泌减少 30%。更重要的是，TA-LNC 在脂多糖诱导的葡萄膜炎（EIU）兔模型中显示出治疗效果，可显著减轻炎症反应的临床症状。这些发现使 TA-LNC 成为治疗眼部疾病更安全、更有效的替代药物。
