Preparation and evaluation of copolymeric micelles with high paclitaxel contents and sustained drug release

In this study, new amphiphilic block copolymers, methoxypoly(ethylene glycol)-b-poly(ε-caprolactone-co-l-lactide) [MPEG-P(CL-co-LLA)] copolymers were designed and synthesized to obtain excellent paclitaxel micellar carriers. The obtained copolymers were characterized by 1H NMR and gel permeation chromatography (GPC). Their water solubility, critical micelle concentration (CMC) and crystallinity were investigated. MPEG2K-P(CL-co-LLA) and MPEG5K-P(CL-co-LLA) had the same molecular weight ratio of hydrophilic and hydrophobic segments, but showed great difference in solubility. MPEG2K-P(CL-co-LLA) micelles could easily be prepared by solid dispersion method while the MPEG5K-P(CL-co-LLA) micelles were difficult to obtain. However, the PTX-loaded micelles made of the two copolymers could be prepared by solid dispersion-sonication method with high drug loading and high encapsulation efficiency. Their drug loadings were up to 36 wt.%. Furthermore, the drug loaded micelles could be lyophilized into powders without the addition of adjuvant and the powders could easily re-dissolve in water to form micelles. The in vitro release data showed a sustained drug release from PTX-loaded micelles for 400 h. Moreover, cytotoxicity results showed that the copolymeric micelles were of great safety and the paclitaxel loaded micelles had antitumor effect, indicating that the copolymers might be promising PTX micellar carriers.