Comparison of Pharmacokinetic Profiles of PM02734 Loaded Lipid Nanoparticles and Cyclodextrins: In Vitro and In Vivo Characterization
Comparison of Pharmacokinetic Profiles of PM02734 Loaded Lipid Nanoparticles and Cyclodextrins: In Vitro and In Vivo Characterization
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DOI：
10.1166/jbn.2012.1420
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发表时间：
2012-08-01
影响因子：
2.9
通讯作者：
Blanco-Prieto, M. J.
中科院分区：
文献类型：
--
作者：
Estella-Hermoso de Mendoza, A.;Calvo, P.;Blanco-Prieto, M. J.
PM02734 是一种化学合成的缩酚肽，源自海洋卡哈拉利德家族，在体外和体内具有广谱抗实体瘤活性，但生物利用度较低。在这项工作中，采用热均质化方法，然后进行高剪切均质化和超声处理，开发了由 Precirol(R) ATO 5 制成的固体脂质纳米颗粒。这些固体脂质纳米颗粒显示出适合口服化合物 PM02734 的尺寸（约 150 nm）和封装效率（接近 70%）。在不同温度条件下储存 6 个月后进行了物理化学稳定性研究，得出的结论是，储存在 4 00 ℃下的固体脂质纳米颗粒比储存在 25 ℃ 下的固体脂质纳米颗粒更稳定。还在 Beagle 犬中评估了载药固体脂质纳米颗粒的药代动力学特征，并通过 AUC、C-max、 和T-max参数估计。基于固体脂质纳米颗粒的制剂比环糊精提供更长的药物持续释放时间。
PM02734 is a chemically synthesized depsipeptide derived from the marine kahalalides family with a broad spectrum of activity against solid tumors in vitro and in vivo, but presenting low bioavailability. In this work, solid lipid nanoparticles made of Precirol(R) ATO 5 have been developed using a hot homogenization method followed by high shear homogenization and ultrasonication. These solid lipid nanoparticles show suitable size (around 150 nm) and encapsulation efficiency (nearly 70%) for the oral administration of the compound PM02734. A physical-chemical stability study was performed after 6 months of storage at different thermical conditions, concluding that solid lipid nanoparticles stored at 4 00 were more stable than solid lipid nanoparticles stored at 25 degrees C. The pharmacokinetic profile of drug-loaded solid lipid nanoparticles was also evaluated in Beagle dogs and compared with that of a cyclodextrin-based delivery system by means of AUC, C-max, and T-max parameter estimation. Solid lipid nanoparticle based formulation provided a sustained release of the drug for a longer period of time than the cyclodextrins.