Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth University, Erandwane, Pune 411038, Maharashtra, India; National Centre for Cell Science, NCCS Complex, Pune University Campus, Ganeshkhind, Pune 411007, Maharashtra, India.
National Centre for Cell Science, NCCS Complex, Pune University Campus, Ganeshkhind, Pune 411007, Maharashtra, India.
Int J Pharm. 2015 Feb 1;479(1):77-87. doi: 10.1016/j.ijpharm.2014.12.044. Epub 2014 Dec 26.
In past years, nanostructured lipid carriers (NLCs) have emerged as novel topical antioxidant delivery systems because of combined positive features of liposomes and polymeric nanoparticles. Here, we seek to unlock the possibility of idebenone (IDB; an antioxidant)-loaded NLCs (IDB-NLCs) cellular interactions such as, viability and uptake, and its photoprotective effects against Ultraviolet-B (UVB)-mediated oxidative stress in immortal human keratinocyte cell line (HaCaT). The two-step preformulation strategy followed by three-level, three-variable, L9 (3(3)) Taguchi robust orthogonal design employed was important in improving IDB-NLCs key physicochemical aspects such as, entrapment efficiency, drug release (sustained), occlusion, skin deposition and physical stability. UV crosslinker, confocal microscopy and flow cytometry techniques were used to (1) mediate oxidative stress in HaCaT cells, (2) study a qualitative cellular uptake, (3) measure intracellular reactive oxygen species (ROS), and mitochondrial membrane potential, respectively. NLCs markedly improved biocompatibility of IDB under normal as well as stress conditions. Quantitative and qualitative cell uptake studies demonstrated a significant uptake of IDB-NLCs (3-fold increase) and nile red-labeled IDB-NLCs (NR-IDB-NLCs) at 2 h, respectively, hence exerted improved photoprotective effects.
在过去的几年中,由于脂质体和聚合物纳米粒的结合优点,纳米结构化脂质载体(NLC)已成为新型局部抗氧化剂递送系统。在这里,我们试图探讨具有抗氧化作用的艾地苯醌(IDB;一种抗氧化剂)负载 NLC(IDB-NLC)的细胞相互作用的可能性,例如细胞活力和摄取,以及其对紫外线-B(UVB)介导的氧化应激的光保护作用在永生化人角质形成细胞系(HaCaT)中。采用两步预配方策略,随后进行三级、三变量、L9(3(3))Taguchi 稳健正交设计,对于改善 IDB-NLC 的关键物理化学性质(如包封效率、药物释放(持续)、闭塞、皮肤沉积和物理稳定性)非常重要。使用紫外光交联剂、共聚焦显微镜和流式细胞术技术分别(1)介导 HaCaT 细胞中的氧化应激,(2)研究定性细胞摄取,(3)测量细胞内活性氧(ROS)和线粒体膜电位。NLC 显著改善了 IDB 在正常和应激条件下的生物相容性。定量和定性细胞摄取研究表明,IDB-NLC(增加 3 倍)和尼罗红标记的 IDB-NLC(NR-IDB-NLC)在 2 小时时具有明显的摄取,从而发挥了更好的光保护作用。