Tatke Akshaya, Dudhipala Narendar, Janga Karthik Yadav, Balguri Sai Prachetan, Avula Bharathi, Jablonski Monica M, Majumdar Soumyajit
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, MS 38677, USA.
Research Institute of Pharmaceutical Sciences, The University of Mississippi, MS 38677, USA.
Nanomaterials (Basel). 2018 Dec 27;9(1):33. doi: 10.3390/nano9010033.
Triamcinolone acetonide (TA), an intermediate acting corticosteroid, is used in the treatment of posterior ocular diseases, such as inflammation, posterior uveitis, and diabetic macular edema. The objective of this investigation was to prepare TA-loaded solid lipid nanoparticles (TA-SLNs) and in situ gel (TA-SLN-IG) formulations for delivery into the deeper ocular tissues through the topical route. TA-SLNs were prepared by hot homogenization and ultrasonication method using glyceryl monostearate and Compritol 888ATO as solid lipids and Tween80 and Pluronic F-68 as surfactants. TA-SLNs were optimized and converted to TA-SLN-IG by the inclusion of gellan gum and evaluated for their rheological properties. transcorneal permeability and ocular distribution of the TA-SLNs and TA-SLN-IG were studied using isolated rabbit corneas and New Zealand albino rabbits, respectively, and compared with TA suspension, used as control (TA-C). Particle size, PDI, zeta potential, assay, and entrapment efficiency of TA-SLNs were in the range of 200⁻350 nm, 0.3⁻0.45, -52.31 to -64.35 mV, 70⁻98%, and 97⁻99%, respectively. TA-SLN-IG with 0.3% gellan gum exhibited better rheological properties. The transcorneal permeability of TA-SLN and TA-SLN-IG was 10.2 and 9.3-folds higher compared to TA-C. TA-SLN-IG showed maximum tear concentration at 2 h, indicating an improved pre-corneal residence time, as well as higher concentrations in aqueous humor, vitreous humor and cornea at 6 h, suggesting sustained delivery of the drug into the anterior and posterior segment ocular tissues, when compared to TA-SLN and TA-C. The results, therefore, demonstrate that the lipid based nanoparticulate system combined with the gelling agents can be a promising drug delivery platform for the deeper ocular tissues.
曲安奈德(TA)是一种中效皮质类固醇,用于治疗眼部后部疾病,如炎症、后葡萄膜炎和糖尿病性黄斑水肿。本研究的目的是制备负载TA的固体脂质纳米粒(TA-SLNs)和原位凝胶(TA-SLN-IG)制剂,以便通过局部途径递送至眼深部组织。采用热均质和超声法,以单硬脂酸甘油酯和Compritol 888ATO为固体脂质,吐温80和泊洛沙姆F-68为表面活性剂制备TA-SLNs。对TA-SLNs进行优化,并通过加入结冷胶将其转化为TA-SLN-IG,并对其流变学性质进行评估。分别使用离体兔角膜和新西兰白化兔研究TA-SLNs和TA-SLN-IG的角膜透过性和眼内分布,并与用作对照的TA混悬液(TA-C)进行比较。TA-SLNs的粒径、多分散指数(PDI)、zeta电位、含量测定和包封率分别在200⁻350 nm、0.3⁻0.45、-52.31至-64.35 mV、70⁻98%和97⁻99%范围内。含有0.3%结冷胶的TA-SLN-IG表现出更好的流变学性质。与TA-C相比,TA-SLN和TA-SLN-IG的角膜透过性分别高10.2倍和9.3倍。TA-SLN-IG在2小时时泪液浓度最高,表明角膜前滞留时间延长,与TA-SLN和TA-C相比,在6小时时房水、玻璃体和角膜中的浓度更高,表明药物可持续递送至眼前段和后段眼组织。因此,结果表明基于脂质的纳米颗粒系统与胶凝剂相结合可以成为用于眼深部组织的有前景的药物递送平台。