초록 |
In order to develop a stable, systemically non-toxic and effective targeted delivery system, Gelatin-DOX (GD) nanoparticle and PEGylated Gelatin-DOX (PGD) nanoparticle were designed and characterized. GD and PGD were synthesized by conjugating gelatin and PEG-epoxide grafted gelatin with doxorubicin, respectively. GD nanoparticle and PGD nanoparticle were prepared in aqueous condition by sonication using a probe-type sonicator at 60 W for 30 min. The nanoparticles were characterized for their particle size in PBS, in vitro stability and degradation, and cytotoxicity and tumor growth inhibition in a murine model in vivo were investigated. The particle size of GD and PGD was 135 and 252 nm at a concentration of 0.5 mg/ml in PBS, respectively, measured by light scattering and the mean diameter of both particles was not changed for 2 days retaining their structure. GD and PGD were specifically cleaved by active MMP-2, which is one of the gelatinases, and had much lower cytotoxicity compared to doxorubicin at the DOX-equivalent concentration against SCC-7 cell line. In vivo, GD and PGD showed significant tumor inhibition compared to control group and doxorubicin treated group. The results of this study show that GD and PGD nanoparticles are stable and possess the antitumor potential in vivo. |