Candesartan cilexetil (CC) is widely used for the treatment of hypertension and heart failure, but it shows very poor aqueous solubility and very low oral absorption. In this work, CC-loaded solid lipid nanoparticles (CLNs) were successfully developed to improve the oral bioavailability. The physicochemical properties of CLNs were characterized, and the pharmacokinetic behavior of CLNs was evaluated in rats. CLNs exhibited nanometer-sized spherical particles with high entrapment efficiency (91.33%). The absorption of CLNs in the stomach was only 2.8% of that in intestine. Moreover, CLNs could be internalized into the enterocytes and then transported into the systemic circulation via the portal circulation and intestinal lymphatic pathway. The pharmacokinetic results indicated that the oral bioavailability of candesartan was obviously improved over 12-fold after incorporation into solid lipid nanoparticles. These results demonstrated that solid lipid nanoparticles have great potential for increasing oral bioavailability of lipophilic drugs such as CC.

From the Clinical Editor

Candesartan cilexetil is a potent angiotensin receptor inhibitor with low bioavailability due to poor aqueous solubility. In this work, solid lipid nanoparticles were used to improve the oral bioavailability 12-fold compared to standard preparation in rats, suggesting that a similar approach might be effective in future human applications.

中文翻译：

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固体脂质纳米粒负载坎地沙坦酯增强了口服生物利用度：大鼠的体外特征和吸收机制

Candesartan cilexetil（CC）被广泛用于治疗高血压和心力衰竭，但其水溶性很差，口服吸收率很低。在这项工作中，成功开发了CC负载的固体脂质纳米颗粒（CLN），以提高口服生物利用度。表征CLNs的理化性质，并评价CLNs在大鼠中的药代动力学行为。CLNs表现出具有高包封率（91.33％）的纳米级球形颗粒。胃中CLN的吸收仅为肠道中的2.8％。此外，CLNs可以内化到肠细胞中，然后通过门脉循环和肠道淋巴途径转运到体循环。药代动力学结果表明，坎地沙坦掺入固体脂质纳米颗粒后的口服生物利用度明显提高了12倍。这些结果表明，固体脂质纳米颗粒具有增加亲脂性药物如CC的口服生物利用度的巨大潜力。

来自临床编辑

Candesartan cilexetil是一种有效的血管紧张素受体抑制剂，由于水溶性差，因此生物利用度低。在这项工作中，使用固体脂质纳米颗粒将大鼠的口服生物利用度与标准制剂相比提高了12倍，这表明类似的方法在未来的人类应用中可能有效。