Solid lipid nanoparticles loading candesartan cilexetil enhance oral bioavailability: in vitro characteristics and absorption mechanism in rats

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 EditorCandesartan 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.

Graphical AbstractCandesartan cilexetil (CC) shows very poor solubility within the physiological pH range and very low oral absorption. In this work, CC-loaded solid lipid nanoparticles (CLNs) were successfully developed. The pharmacokinetic results indicated that the peak concentration of candesartan from CLNs was 27 times higher than that from free-CC suspension, and the oral bioavailability of CC was markedly improved over 12-fold after incorporated into solid lipid nanoparticles (SLNs). These results indicated that SLNs demonstrated great potential for increasing oral delivery of lipophilic drugs such as CC.Figure optionsDownload high-quality image (182 K)Download as PowerPoint slide