Preparation and characterization of cisplatin-incorporated gelatin nanocomplex for cancer treatment
Journal
Current Nanoscience
Journal Volume
7
Journal Issue
6
Pages
932-937
Date Issued
2011
Author(s)
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. ? 2011 Bentham Science Publishers.
Subjects
Cancer; Cisplatin (CDDP); Drug delivery; Gelatin nanoparticle (GPs); Ion change
SDGs
Other Subjects
A549 cells; Anticancer effects; Cancer; Cancer models; Carboxyl groups; Cisplatin; Desolvation process; Drug-conjugates; Drug-release rate; Gelatin nanoparticles; Gelatin solutions; Glutaraldehydes; Human lung carcinoma cells; In-vivo; Ion change; Nanocomplexes; Potential drug; Reduced toxicity; Side effect; Synthesis parameters; Systematic investigations; Thermal gravimetric analysis; Time points; Toxic effect; Tumor size; Aldehydes; Cells; Chemotherapy; Differential thermal analysis; Diseases; Drug delivery; Drug products; Fourier transform infrared spectroscopy; Functional polymers; Gravimetric analysis; Ion exchange; Mammals; Nanoparticles; Platinum compounds; Thermogravimetric analysis; Toxicity; Tumors; X ray diffraction; X ray diffraction analysis; Platinum; carboxyl group; cisplatin; gelatin; glutaraldehyde; nanocarrier; nanoparticle; polymer; animal experiment; animal model; animal tissue; antineoplastic activity; article; cancer chemotherapy; cancer survival; controlled study; differential scanning calorimetry; drug cytotoxicity; drug delivery system; drug release; in vitro study; in vivo study; infrared spectroscopy; ion exchange; morphology; mouse; nanofabrication; nonhuman; particle size; pH; physical chemistry; priority journal; subcutaneous cancer; subcutaneous tissue tumor; surface charge; survival rate; temperature; thermogravimetry; tumor volume; X ray diffraction; zeta potential
Type
journal article