Almeida Hugo, Lobão Paulo, Frigerio Christian, Fonseca Joel, Silva Renata, Sousa Lobo José Manuel, Amaral Maria Helena
a Laboratory of Pharmaceutical Technology, Department of Drug Sciences , Faculty of Pharmacy, Research Centre for Pharmaceutical Sciences, University of Porto , Porto , Portugal.
b Department of Chemistry and Biochemistry , Faculty of Sciences, University of Porto , Porto , Portugal.
Pharm Dev Technol. 2017 May;22(3):336-349. doi: 10.3109/10837450.2015.1125922. Epub 2015 Dec 20.
Nanostructured lipid carrier (NLC) dispersions present low viscosity and poor mucoadhesive properties, which reduce the pre-corneal residence time and consequently, the bioavailability of ocular drugs.
The aim of this study was to prepare thermoresponsive eyedrops based on the combination of lipid nanoparticles and a thermoresponsive polymer with mucomimetic properties (Pluronic® F-127).
NLC dispersions were prepared based on the melt-emulsification and ultrasonication technique. Physicochemical and morphological characteristics of the colloidal dispersions were evaluated. The formulation was also investigated for potential cytotoxicity in Y-79 human retinoblastoma cells and the in vitro drug release profile of the ibuprofen was determined.
NLC showed a Z-average below 200 nm, a highly positive zeta potential and an efficiency of encapsulation (EE) of ∼90%. The gelification of the NLC dispersion with 15% (w/w) Pluronic® F-127 did not cause significant changes to the physicochemical properties. The potential NLC-induced cytotoxicity was evaluated by the Alamar Blue reduction assay in Y-79 cells, and no relevant cytotoxicity was observed after exposure to 0-100 µg/mL NLC for up to 72 hours. The optimized formulations showed a sustained release of ibuprofen over several hours.
The strategy proposed in this work can be successfully used to increase the bioavailability and the therapeutic efficacy of conventional eyedrops.
纳米结构脂质载体（NLC）分散体具有低粘度和较差的粘膜粘附性，这会缩短角膜前滞留时间，从而降低眼部药物的生物利用度。
本研究的目的是基于脂质纳米颗粒和具有拟粘液特性的热响应性聚合物（普朗尼克®F-127）的组合制备热响应性眼药水。
基于熔融乳化和超声技术制备NLC分散体。评估了胶体分散体的物理化学和形态特征。还研究了该制剂对Y-79人视网膜母细胞瘤细胞的潜在细胞毒性，并测定了布洛芬的体外药物释放曲线。
NLC的Z均粒径低于200nm，zeta电位高度为正，包封效率（EE）约为90%。含有15%（w/w）普朗尼克®F-127的NLC分散体凝胶化对其物理化学性质没有显著影响。通过Alamar Blue还原试验评估了NLC在Y-79细胞中潜在的细胞毒性，在暴露于0-100μg/mL NLC长达72小时后未观察到相关细胞毒性。优化后的制剂显示布洛芬在数小时内持续释放。
本研究中提出的策略可成功用于提高传统眼药水的生物利用度和治疗效果。
