Polymeric micelles based on poly(ethylene glycol) block poly(racemic amino acids) hybrid polypeptides: conformation-facilitated drug-loading behavior and potential application as effective anticancer drug carriers.

In this work, racemic hybrid polypeptides poly(ethylene glycol) (PEG)-b-poly(racemic-leucine) (PRL) copolymers with different leucine residues have been synthesized and characterized. Using docetaxel as a model molecule, the high drug-loaded spherical micelles based on PEG-PRL were prepared successfully using dialysis, with a tunable particle size from 170 nm to 250 nm obtained by changing the length of the hydrophobic blocks. Facilitated drug-loading behavior (higher drug-loading ability and easier drug-loading process) of PEG-PRL compared with their corresponding levo forms (PEG-b-poly[levo leucine]) was observed and clarified for the first time. With this facilitation, the highest drug-loading content and efficiency of PEG-PRL micelles can achieve 11.2% ± 0.4% and 67.2% ± 2.4%, respectively. All drug-loaded PEG-PRL micelles exhibit a similar release behavior with a sustained release up to 72 hours. The PEG-PRL was shown to be nontoxic against MCF-7 and human umbilical vein endothelial cells up to a concentration of 100 µg/mL, displaying a good biocompatibility. Also, the docetaxel-loaded PEG-PRL micelles were more toxic than the free drug against MCF-7 human breast cancer cells - both dose and time dependent. Therefore, these high docetaxel-loaded micelles based on racemic hybrid polypeptides appear to be a novel promising nanomedicine for anticancer therapy.

Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats.

Berberine chloride (BBR) is a natural isoquinoline alkaloid extracted from medicinal herbs. It has been reported that the intestinal absorption of BBR is very low. In this study, the absolute bioavailability of BBR was studied, and the enhancing effects of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on intestinal absorption were investigated in rats. BBR injection was administrated via the femoral vein at a dose of 1.0 mg kg(-1) in intravenous group, and BBR oral formulations were administrated by oral gavage at a dose of 100 mg kg(-1) in BBR control (control) group and BBR-TPGS (test) group, respectively. The result showed that BBR had a very low absolute bioavailability of 0.68%, and TPGS could enhance intestinal absorption of BBR significantly. TPGS at a concentration of 2.5% could improve peak concentration (C(max)) and area under the curve (AUC(0-36)) of BBR by 2.9 and 1.9 times, respectively. The absorption enhancing ability of TPGS may be due to its ability to affect the biological activity of P-glycoprotein and thereby reduce the excretion of absorbed BBR into the intestinal lumen. This study indicated that absolute bioavailability of BBR was 0.68% in rats, and TPGS was a good absorption enhancer capable of enhancing intestinal absorption of BBR significantly.