Magalhães Joana, L Chaves Luise, C Vieira Alexandre, G Santos Susana, Pinheiro Marina, Reis Salette
LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal.
i3S-Instituto de Investigação e Inovação em Saúde, INEB-Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal.
Pharmaceutics. 2020 Jan 17;12(1):75. doi: 10.3390/pharmaceutics12010075.
This work aims to optimize and assess the potential use of lipid nanoparticles, namely nanostructured lipid carriers (NLCs), as drug delivery systems of rifapentine (RPT) for the treatment of tuberculosis (TB). A Box-Behnken design was used to increase drug encapsulation efficiency (EE) and loading capacity (LC) of RPT-loaded NLCs. The optimized nanoparticles were fully characterized, and their effect on cell viability was assessed. The quality-by-design approach allowed the optimization of RPT-loaded NLCs with improved EE and LC using the minimum of experiments. Analyses of variance were indicative of the validity of this model to optimize this nanodelivery system. The optimized NLCs had a mean diameter of 242 ± 9 nm, polydispersity index <0.2, and a highly negative zeta potential. EE values were higher than 80%, and differential scanning calorimetry analysis enabled the confirmation of the efficient encapsulation of RPT. Transmission electron microscopy analysis showed spherical nanoparticles, uniform in shape and diameter, with no visible aggregation. Stability studies indicated that NLCs were stable over time. No toxicity was observed in primary human macrophage viability for nanoparticles up to 1000 μg mL. Overall, the optimized NLCs are efficient carriers of RPT and should be considered for further testing as promising drug delivery systems to be used in TB treatment.
本研究旨在优化和评估脂质纳米颗粒，即纳米结构脂质载体（NLCs）作为利福喷汀（RPT）药物递送系统用于治疗结核病（TB）的潜在用途。采用Box-Behnken设计提高载RPT的NLCs的药物包封率（EE）和载药量（LC）。对优化后的纳米颗粒进行了全面表征，并评估了它们对细胞活力的影响。质量源于设计方法允许使用最少的实验来优化载RPT的NLCs，提高其EE和LC。方差分析表明该模型对于优化这种纳米递送系统是有效的。优化后的NLCs平均直径为242±9nm，多分散指数<0.2，且具有高度负的zeta电位。EE值高于80%，差示扫描量热法分析证实了RPT的有效包封。透射电子显微镜分析显示纳米颗粒呈球形，形状和直径均匀，无可见聚集。稳定性研究表明NLCs随时间稳定。对于浓度高达1000μg/mL的纳米颗粒，在原代人巨噬细胞活力方面未观察到毒性。总体而言，优化后的NLCs是RPT的有效载体，作为用于TB治疗的有前景的药物递送系统应考虑进一步测试。
