PDF(Pubmed)
Abstract：
Simvastatin (SVA) is a well-prescribed drug for treating cardiovascular and hypercholesterolemia. Due to the extensive hepatic first-pass metabolism and poor solubility, its oral bioavailability is 5%. Solid lipid nanoparticles (SLNs) and hydrogel-coated SLNs were investigated to overcome the limited bioavailability of SVA. Four different lipids used alone or in combination with two stabilizers were employed to generate 13 SLNs. Two concentrations of chitosan (CS) and alginate (AL) were coating materials. SLNs were studied for particle size, zeta potential, in vitro release, rheology, and bioavailability. The viscosities of both the bare and coated SLNs exhibited shear-thinning behavior. The viscosity of F11 (Chitosan 1%) at 20 and 40 rpm were 424 and 168 cp, respectively. F11 had a particle size of 260.1 ± 3.72 nm with a higher release; the particle size of F11-CS at 1% was 524.3 ± 80.31 nm. In vivo studies illustrated that F11 had the highest plasma concentration when compared with the SVA suspension and coated chitosan (F11 (Chitosan 1%)). Greater bioavailability is measured as (AUC0→24), as compared to uncoated ones. The AUC for F11, F11-CS 1%, and the SVA suspension were 1880.4, 3562.18, and 272 ng·h/mL, respectively. Both bare and coated SLNs exhibited a significantly higher relative bioavailability when compared to that from the control SVA.
摘要：
辛伐他汀（SVA）是治疗心血管和高胆固醇血症的良好处方药物。由于广泛的肝首过代谢和溶解性差，其口服生物利用度为5%。研究了固体脂质纳米颗粒（SLN）和水凝胶包被的SLN，以克服SVA的有限生物利用度。使用单独使用或与两种稳定剂组合使用的四种不同脂质以产生13种SLN。两种浓度的壳聚糖(CS)和藻酸盐(AL)为涂层材料。研究了SLN的粒径，zeta电位,体外释放，流变学,和生物利用度。裸露和涂覆的SLN的粘度均表现出剪切稀化行为。F11（壳聚糖1％）在20和40rpm下的粘度分别为424和168cp，分别。F11的粒度为260.1±3.72nm,具有较高的释放;1%时F11-CS的粒度为524.3±80.31nm。体内研究表明，与SVA悬浮液和包被的壳聚糖（F11（壳聚糖1％））相比，F11的血浆浓度最高。更大的生物利用度被测量为(AUC0→24)，与无涂层的相比。F11，F11-CS1%的AUC，SVA悬浮液为1880.4、3562.18和272ng·h/mL，分别。当与对照SVA相比时,裸露的和涂覆的SLN都表现出显著更高的相对生物利用度。
