Abstract：
UNASSIGNED: Lipid-based drug delivery systems (DDS) can improve the pharmacokinetic (PK) parameters of some drugs. Especially those with a high volume of distribution (Vd) leading to off-target accumulation and toxicity. Amiodarone as an anti-arrhythmic agent induces hypothyroidism and liver disorders limiting its clinical indication.
UNASSIGNED: In the present study, amiodarone PK parameters and biodistribution after IV administration of four nano-formulations to rats were compared. The formulations were liposomes, solid lipid nanoparticles (SLN), PEGylated SLN (PEG-SLN), and nanoemulsions (NE). All formulations were optimized.
UNASSIGNED: The nanoparticles were spherical with a diameter of 100-200 nm and sustained in vitro drug release in buffer pH 7.4. The best-fitted model for the plasma concentration-time profile was two-compartmental. In vivo studies indicated the most changes in PKs induced after liposome, SLN, and NE administration, respectively. The area under the curve (AUC) and maximum plasma concentration (Cmax) of liposomes, SLN, and NE were 22.5, 2.6, 2.46 times, and 916, 58, and 26 times higher than that of amiodarone solution, respectively (P-value<0.05). The heart-to-liver ratio of amiodarone was higher for nano-formulations compared to drug solution except for liposomes.
UNASSIGNED: Lipid-based particles can improve the PK parameters of amiodarone and its distribution in different tissues.
UNASSIGNED: In the present study, amiodarone PK parameters and biodistribution after IV administration of four nano-formulations to rats were compared. The formulations were liposomes, solid lipid nanoparticles (SLN), PEGylated SLN (PEG-SLN), and nanoemulsions (NE). All formulations were optimized.
UNASSIGNED: The nanoparticles were spherical with a diameter of 100-200 nm and sustained in vitro drug release in buffer pH 7.4. The best-fitted model for the plasma concentration-time profile was two-compartmental. In vivo studies indicated the most changes in PKs induced after liposome, SLN, and NE administration, respectively. The area under the curve (AUC) and maximum plasma concentration (Cmax) of liposomes, SLN, and NE were 22.5, 2.6, 2.46 times, and 916, 58, and 26 times higher than that of amiodarone solution, respectively (P-value<0.05). The heart-to-liver ratio of amiodarone was higher for nano-formulations compared to drug solution except for liposomes.
UNASSIGNED: Lipid-based particles can improve the PK parameters of amiodarone and its distribution in different tissues.
摘要：
■基于脂质的药物递送系统（DDS）可以改善某些药物的药代动力学（PK）参数。尤其是那些具有高体积分布(Vd)的,导致脱靶积累和毒性。胺碘酮作为抗心律失常剂可引起甲状腺功能减退和肝脏疾病，从而限制了其临床适应症。
■在本研究中，比较了大鼠静脉注射四种纳米制剂后的胺碘酮PK参数和生物分布。配方是脂质体，固体脂质纳米粒（SLN），聚乙二醇化SLN（PEG-SLN），和纳米乳液(NE)。优化所有配方。
■纳米颗粒为球形，直径为100-200nm，在pH7.4的缓冲液中体外持续释放药物。血浆浓度-时间曲线的最佳拟合模型是两室。体内研究表明脂质体后引起的PKs变化最大，SLN,和NE管理，分别。脂质体的曲线下面积（AUC）和最大血浆浓度（Cmax），SLN,NE分别为22.5、2.6、2.46倍，比胺碘酮溶液高916、58和26倍，分别为(P值<0.05)。除脂质体外，纳米制剂的胺碘酮的心肝比高于药物溶液。
■基于脂质的颗粒可以改善胺碘酮的PK参数及其在不同组织中的分布。
■在本研究中，比较了大鼠静脉注射四种纳米制剂后的胺碘酮PK参数和生物分布。配方是脂质体，固体脂质纳米粒（SLN），聚乙二醇化SLN（PEG-SLN），和纳米乳液(NE)。优化所有配方。
■纳米颗粒为球形，直径为100-200nm，在pH7.4的缓冲液中体外持续释放药物。血浆浓度-时间曲线的最佳拟合模型是两室。体内研究表明脂质体后引起的PKs变化最大，SLN,和NE管理，分别。脂质体的曲线下面积（AUC）和最大血浆浓度（Cmax），SLN,NE分别为22.5、2.6、2.46倍，比胺碘酮溶液高916、58和26倍，分别为(P值<0.05)。除脂质体外，纳米制剂的胺碘酮的心肝比高于药物溶液。
■基于脂质的颗粒可以改善胺碘酮的PK参数及其在不同组织中的分布。
