Shape-Controlled Paclitaxel Nanoparticles with MultipleMorphologies: Rod-Shaped Worm-Like Spherical and Fingerprint-Like

摘要

Although many nanocarriers have been developed to encapsulate paclitaxel (PTX), the drug loading and circulation time in vivo always are not ideal because of its rigid “brickdust” molecular structure. People usually concentrate their attention on the spherical nanocarriers, here paclitaxel nanoparticles with different geometries were established through the chemical modification of PTX, nanoprecipitation, and core-matched cargos. Previously we have developed rod-shape paclitaxel nanocrystals using block copolymer, pluronic F127. Unfortunately, the pharmacokinetic (PK) profile of PTX nanocrystals is very poor. However, when PTX was replaced by its prodrug, the geometry of the nanoparticles changed from rod-shaped to worm-like. The worm-like nanoparticles can be further changed to spherical nanoparticles using the nanoprecipitation method, and changed to fingerprint-like nanoparticles upon the addition of the core-matched PTX. The nanoparticles with nonspherical morphologies, including worm-like nanoparticles and fingerprint-like nanoparticles, offer significant advantages in regards to key PK parameters in vivo. More important, in this report the application of the core-matching technology in creating a core-matched environmentcapable of controlling the in vivo PK of paclitaxelwas demonstrated, and it revealed a novel technique platform to constructnanoparticles and improve the poor PK profiles of the drugs.