Drug-loaded micelles based on hyaluronic acid-paclitaxel prodrug: preparation and pharmacokinetic study in rats

WANG Jing; HUO Meirong; ZHOU Jianping; ZHANG Yong; ZHANG Xuyuan; WANG Lei; YIN Tingjie

doi:10.11665/j.issn.1000-5048.20130606

Journal of China Pharmaceutical University > 2013 > 44(6): 520-525. > DOI: 10.11665/j.issn.1000-5048.20130606

WANG Jing, HUO Meirong, ZHOU Jianping, ZHANG Yong, ZHANG Xuyuan, WANG Lei, YIN Tingjie. Drug-loaded micelles based on hyaluronic acid-paclitaxel prodrug: preparation and pharmacokinetic study in rats[J]. Journal of China Pharmaceutical University, 2013, 44(6): 520-525. DOI: 10.11665/j.issn.1000-5048.20130606

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Drug-loaded micelles based on hyaluronic acid-paclitaxel prodrug: preparation and pharmacokinetic study in rats

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Abstract

The aims of this study were to prepare high paclitaxel loading amount polymeric micelles based on amphiphilic hyaluronic acid-paclitaxel prodrug. The drug-loading and entrapment efficiency were characterized by HPLC. The physico-chemical properties of PTX loaded HA-PTX micelles(PTX-HA-PTX)was characterized by dynamic light scattering(DLS), transmission electron microscope(TEM), atomic force microscopy(AFM)and X-ray diffraction(XRD), respectively. The critical micelle concentration(CMC)was determined by fluorescence pyrene probe techniques. The pharmacokinetics behaviors of PTX-HA-PTX micelles were performed in rats taking Taxol as control. It was found that the drug-loading and encapsulation efficiency of PTX-HA-PTX micelles reached up to 41. 8% and 95. 4%, respectively. The nanoparticle size was approximately 213. 2 nm and the Zeta potential was -15. 5 mV. PTX-HA-PTX micelles exhibited to be almost spherical in shape from the observation by TEM and AFM. XRD results confirmed that PTX was either molecularly dispersed in the polymers or distributed in the micelles in an amorphous state. In pharmacokinetic studies, the AUC value of PTX-HA-PTX micelles increased significantly(P< 0. 01)while the CL value decreased significantly(P< 0. 05)compared with Taxol, which indicated slower clearance rate, prolonged residence time and enhanced therapeutic effect. All the results demonstrated that PTX-HA-PTX micelles might be a promising PTX delivery carrier for efficient tumor therapy.
- hyaluronic acid,
- paclitaxel,
- micelles,
- prodrug,
- conjugates,
- pharmacokinetics

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