Characterization, in vitro release and pharmacokinetics of Paclitaxel-loaded PEGylated Carboxymethyl Chiosan-Rhein Conjugate Micelles

OBJECTIVE To characterize the morphology and structure of PEGylated carboxymethyl chiosan-rhein conjugate(polymeric) micelles loaded with paclitaxel(PTX)(PTX/CRmP micelles), and to investigate the release in vitro and pharmacokinetic characteristics of PTX/CRmP micelles. METHODS Transmission electron microscopy(TEM), differential scanning calorimetry(DSC), X-ray diffraction(XRD) were used to evaluate the particle size, morphology and structure of micelles. The in vitro release of PTX/CRmP micelles was studied in pH 7.4 phosphate buffer solution(containing 0.8 mol·L^-1 sodium salicylate) to calculate the cumulative release rate of PTX and draw the cumulative release curve. The pharmacokinetics of PTX/CRmP micelles were studied by concentration-time curve and pharmacokinetic parameters after they were injected into the tail vein of rats. RESULTS TEM showed that PTX/CRmP micelles were spherical, with a particle size of about 160 nm and uniform distribution. DSC and XRD showed that PTX was almost all loaded into the core of CPmP micelles. The cumulative release of PTX/CRmP micelles in pH 7.4 PBS (containing 0.8 mol·L^-1 sodium salicylate) was 92.2% within 24 h, significantly slower than that of Taxol^®. In pharmacokinetic studies, drug distribution and elimination in PTX/CRmP micelles group were slower and AUC was enhanced. The CRmP micelles could prolong the half-life and circulation time of PTX in the blood circulation system. CONCLUSION PTX/CRmP micelles are obtained by physically encapsulating PTX in the cores of CRmP micelles, with a small particle size and slow PTX release in the simulated blood pH environment in vitro. The bioavailability of PTX is improved.