Preparation and characteristics of TPGS-CS/PTX polymeric micelles and its in vivo intestines absorption in rats / 中草药

ABSTRACT

Objective To obtain the intestines absorption of TPGS-CS/PTX polymeric micelles in rats, a drug-loaded micelle system was established by a kind of amphiphilic copolymer, D-α-tocopherol polyethylene glycol 1000 succinate-chitosan (TPGS-CS) was prepared by grafting D-α-tocopherol polyethyleneglycol 1000 succinate (TPGS) as the donor of the micelle hydrophobic group on chitosan (CS) as bioadhesive material, and loading paclitaxel as model drug. Methods TPGS was activated by its hydroxy-terminal carboxylation with succinic anhydride (SA) and 4-dimethylaminopyridine (DMAP). The TPGS-CS copolymer was prepared by the amidation of free amino groups on CS. The chemical structure of the TPGS-CS grafted copolymer was characterized by Fourier transform-infrared spectroscopy (FT-IR) and Nuclear magnetic resonance spectroscopy (NMR). The polymer micelle loading paclitaxel was selected as model drug and TPGS-CS/PTX was prepared by ultrasonic emulsification method. The encapsulation efficacy (EE) and drug loading (DL) were determined by high performance liquid chromatography (HPLC). The particle size, Zeta potential, and size distribution of the micelle system were measured by dynamic light scattering (DLS). The surface morphology of the micelles was investigated by Transmission electron microscopy (TEM). The in vivo intestines absorption rate (Ka) of paclitaxel-loaded TPGS-CS micelle was calculated in rats. Results The results of FT-IR and 1H NMR indicated that the copolymer (TPGS-CS) was synthesized. The TEM result showed that the formed particles were uniform in shape without aggregation. The Ka of TPGS-CS/PTX was 20 percent higher in comparison to the reference preparation, it indicated that this polymeric micelles could increase bioavailability. Conclusion The proposed TPGS-CS copolymer was successfully synthesized in this experiment, and the drug-loaded micelles prepared by ultrasonic emulsification exhibited good characteristics compared with the reference preparation, the Ka of paclitaxel was increased to some extent to promote oral absorption of the drug.