The present research work was aimed to develop and optimize the nanostructured lipid carrier (NLCs) of the antihypertensive drug lacidipine (LAC) for the improvement of oral bioavailability and antihypertensive activity. LAC-NLCs were successfully developed by the preemulsion probe sonication technique. The formulations were optimized by Box-Behnken design and assessed for particle size (PS), polydispersity index (PDI), entrapment efficiency (EE), drug loading (DL), drug release, ex vivo permeation, and in vivo study. The optimized LAC-NLCs showed nanometric PS (191.0 ± 5.89 nm), high EE (90% ± 3.69%) and DL (9.26% ± 1.89%), negative zeta potential (−28.9 ± 0.99 mV), and narrow size distribution (PDI of 0.074 ± 0.013) with spherical morphology. The drug release study revealed that a significantly (p < 0.05) higher LAC release (88.49% ± 3.01%) was achieved from the optimized LAC-NLCs compared to LAC-dispersion (34.27% ± 3.01%). Moreover, the optimized LAC-NLCs showed significantly (p < 0.05) higher intestinal permeation (692.04 ± 19.76 μg) than LAC-dispersion (23.83 ± 5.08 μg). After oral administration of a single dose of LAC, the optimized LAC-NLCs exhibited 3.45-fold higher relative oral bioavailability as well as a more prominent antihypertensive effect than LAC-dispersion. This might be due to the high penetration and absorption of the drug. Hence, NLCs might provide an efficient nano delivery for the management of hypertension and promising drug delivery systems for the bioavailability enhancement of LAC.

中文翻译：

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拉西地平脂质基纳米载体的配方用于改善口服给药：Box-Behnken 设计优化、体外、离体和临床前评估

目前的研究工作旨在开发和优化抗高血压药物拉西地平（LAC）的纳米结构脂质载体（NLC），以提高口服生物利用度和抗高血压活性。LAC-NLCs 是通过预乳液探针超声技术成功开发的。配方通过 Box-Behnken 设计进行了优化，并评估了粒径 (PS)、多分散指数 (PDI)、包封效率 (EE)、载药量 (DL)、药物释放、离体渗透和体内学习。优化的 LAC-NLC 显示出纳米级 PS (191.0 ± 5.89 nm)、高 EE (90% ± 3.69%) 和 DL (9.26% ± 1.89%)、负 zeta 电位 (-28.9 ± 0.99 mV) 和窄尺寸分布 ( PDI 为 0.074 ± 0.013)，具有球形形态。药物释放研究表明，与 LAC 分散体 (34.27% ± 3.01%) 相比，优化的 LAC-NLC 的 LAC 释放 (88.49% ± 3.01%)显着提高 ( p < 0.05)。此外，优化的 LAC-NLC 显示出显着的 ( p< 0.05) 比 LAC 分散体 (23.83 ± 5.08 μg) 更高的肠道渗透率 (692.04 ± 19.76 μg)。口服单剂量 LAC 后，优化后的 LAC-NLC 表现出比 LAC 分散剂高 3.45 倍的相对口服生物利用度以及更显着的抗高血压作用。这可能是由于药物的高渗透和吸收。因此，NLC 可能为高血压的管理提供有效的纳米递送，并为提高 LAC 的生物利用度提供有前景的药物递送系统。