Albumin nanoparticles for glutathione-responsive release of cisplatin: New opportunities for medulloblastoma

Publication date: 30 January 2017 Source:International Journal of Pharmaceutics, Volume 517, Issues 1–2 Author(s): Giuseppina Catanzaro, Manuela Curcio, Giuseppe Cirillo, Umile Gianfranco Spizzirri, Zein Mersini Besharat, Luana Abballe, Alessandra Vacca, Francesca Iemma, Nevio Picci, Elisabetta Ferretti Redox-responsive nanoparticles were synthesized by desolvation of bovine serum albumin followed by disulfide-bond crosslinking with N, Nʹ-Bis (acryloyl) cystamine. Dynamic light scattering and transmission electron microscopy studies revealed spherical nanoparticles (mean diameter: 83nm, polydispersity index: 0.3) that were glutathione-responsive. Confocal microscopy revealed rapid, efficient internalization of the nanoparticles by Daoy medulloblastoma cells and healthy controls (HaCaT keratinocytes). Cisplatin-loaded nanoparticles with drug:carrier ratios of 5%, 10%, and 20% were tested in both cell lines. The formulation with the highest drug:carrier ratio reduced Daoy and HaCaT cell viability with IC50 values of 6.19 and 11.17μgmL−1, respectively. The differential cytotoxicity reflects the cancer cells’ higher glutathione content, which triggers more extensive disruption of the disulfide bond-mediated intra-particle cross-links, decreasing particle stability and increasing their cisplatin release. These findings support continuing efforts to improve the safety and efficacy of antineoplastic drug therapy for pediatric brain tumors using selective nanopart...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research