Mura Paola, Maestrelli Francesca, D'Ambrosio Mario, Luceri Cristina, Cirri Marzia
Department of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
Department of Neurofarba, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Pharmaceutics. 2021 Mar 24;13(4):437. doi: 10.3390/pharmaceutics13040437.
The aim of this study was the optimization of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in terms of physicochemical and biopharmaceutical properties, to develop effective and stable aqueous liquid formulations of hydrochlorothiazide, suitable for paediatric therapy, overcoming its low-solubility and poor-stability problems. Based on solubility studies, Precirol ATO5 and Transcutol HP were used as solid and liquid lipids, respectively. The effect of different surfactants, also in different combinations and at different amounts, on particle size, homogeneity and surface-charge of nanoparticles was carefully investigated. The best formulations were selected for drug loading, and evaluated also for entrapment efficiency and release behaviour. For both SLN and NLC series, the use of Gelucire 44/14 as surfactant rather than PluronicF68 or Tween 80 yielded a marked particle size reduction (95-75 nm compared to around 600-400 nm), and an improvement in entrapment efficiency and drug release rate. NLC showed a better performance than SLN, reaching about 90% entrapped drug (vs. 80%) and more than 90% drug released after 300 min (vs. about 65%). All selected formulations showed good physical stability during 6-month storage at 4 °C, but a higher loss of encapsulated drug was found for SLNs (15%) than for NLCs (<5%). Moreover, all selected formulations revealed the absence of any cytotoxic effect, as assessed by a cell-viability test on Caco-2 cells and are able to pass the intestinal epithelium as suggested by Caco-2 uptake experiments.
本研究的目的是在物理化学和生物药剂学性质方面优化固体脂质纳米粒（SLN）和纳米结构脂质载体（NLC），以开发有效且稳定的氢氯噻嗪水性液体制剂，适用于儿科治疗，克服其低溶解度和稳定性差的问题。基于溶解度研究，分别使用Precirol ATO5和Transcutol HP作为固体和液体脂质。仔细研究了不同表面活性剂（不同组合和不同用量）对纳米粒粒径、均匀性和表面电荷的影响。选择最佳制剂进行药物负载，并评估其包封率和释放行为。对于SLN和NLC系列，使用Gelucire 44/14作为表面活性剂而非PluronicF68或吐温80可显著降低粒径（从约600 - 400 nm降至95 - 75 nm），并提高包封率和药物释放速率。NLC表现优于SLN，包封药物达到约90%（SLN为80%），300分钟后药物释放超过90%（SLN约为65%）。所有选定制剂在4℃储存6个月期间均表现出良好的物理稳定性，但SLN的包封药物损失率（15%）高于NLC（<5%）。此外，通过对Caco - 2细胞的细胞活力测试评估，所有选定制剂均未显示出任何细胞毒性作用，并且如Caco - 2摄取实验所示，能够穿过肠上皮。
