Preparation and quality evaluation of comet-shaped hydroxy camptothecin-loaded amphiphilic block copolymer / 药学学报

ABSTRACT

In this study, we used Shirasu porous glass membrane (SPG) as a template and hydroxy camptothecin (HCPT) as a model drug to prepare the comet-shaped MePEG[methoxyl poly(ethylene glycol)]-PLGA[poly(lactic-co-glycolic acid)-HCPT amphiphilic block copolymer. Our method was optimized by the orthogonal design method. The partical size, zeta potential, drug-loaded content, yield, shape and status of the obtained comet-shaped MePEG-PLGA-HCPT particles were further characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM)/transmission electron microscopy (TEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) et al, respectively. In vitro release was preliminary evaluated. MTT assay to preliminary evaluate the cytotoxicity of particles against human liver BEL-7402 cells. Based on these experimental results, the optimal preparation conditions containweight ratio of HCPT to MePEG-PLGA was 11, nitrogen pressure was 100 kPa and SPG membrane pore size was 1.1 μm. The particles exhibited a comet-shaped shape, fairly uniform size and were well dispersed. The drug-loading content was 46.2%, with yield of 96.4%, and zeta -31.4 mV. The distribution of HCPT in particles was very uniform, and HCPT showed a amorphous state existed in particles. The release behavior in vitro showed sustained releasing,and with the drug loading content in proportion to the release of the drug. MTT test indicated that the HCPT-loaded comet-shaped particles had enhanced the cytotoxicity against human liver BEL-7402 cells relatively to the HCPT-loaded spherical particles in vitro. The results showed a promising potential application of the preparation in clinical treatment of tumor.