Comparison of Pharmacokinetic Profiles of Pm02734 Loaded Lipid Nanoparticles and Cyclodextrins: in Vitro and in Vivo Characterization

Autores: Estella Hermoso de Mendoza, Ander; Calvo, P.; Bishop, A.; Aviles, P.; Blanco Prieto, María José
ISSN: 1550-7033
Volumen: 8
Número: 4
Páginas: 703-708
Fecha de publicación: 2012
Lugar: WOS
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.