Abstract
To develop a polymer – anticancer drug conjugate accompanied by a reduction of anticipated side effects and therapeutic improvement, we employed gelatin nanoparticles (GPs) as carriers for cisplatin (CDDP). The GPs-cisplatin nanocomplex (GP-Pt) was fabricated by a two-step desolvation process from gelatin type A. The parameters for the optimal GP-Pt preparation were investigated, including temperature, the pH of the gelatin solution, glutaraldehyde (GA) concentration, and the time point for CDDP addition. GP-Pt was characterized by its size, surface charge, morphology, and drug release rate. The chemical and physical properties of GP-Pt have been studied using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), differential thermal analysis (DTA), and thermal gravimetric analysis (TGA). In vivo anticancer effects and reductions in toxicity were evaluated by intratumorally injecting GP-Pt into SCID mice that had been injected with human lung carcinoma cells (A549 cells) as a subcutaneous cancer model. The GP-Pt prepared with gelatin type A solution at pH 2.5 with a 0.4 % GA addition achieved the smallest size. The FT-IR assay result showed that GPs conjugated with cisplatin via an ion-exchange of the carboxyl group of the gelatin. In vivo anticancer effects were revealed in that GP-Pt could effectively decrease the tumor size, and mice treated with GP-Pt lived longer than those treated with free CDDP, which indicates reduced toxicity due to cisplatin. The systematic investigation of the synthesis parameters showed that it is possible to prepare GPs with a small size distribution and with the incorporation of high cisplatin. We showed that the GP-Pt nanocomplex was less toxic than the free drug, and that it could effectively reduce the tumor size and toxic effects in mice grafted with A549 cells. The results of this study suggest that GP-Pt could be slowly released to reduce the toxicity of cisplatin, and that it may be used as a potential drug delivery system for chemotherapy.
Keywords: Gelatin nanoparticle (GPs), cisplatin (CDDP), ion change, drug delivery, cancer, Nanocomplex, Anticancer Effect
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